General Biochemistry

    • chemistry : the science that treats of the elements and atomic relations of matter, and of the various compounds of the elements.
      • mineral or inorganic chemistry : that branch of the science of chemistry which deals with compounds that do not occur in the plant or animal worlds
      • organic chemistry : that branch of chemistry which deals with compounds that contain carbon.
      • detritus : particulate matter produced by or remaining after the wearing away or disintegration of a substance or tissue; designated as organic or nonorganic, depending on the nature of the original material
        • biodetritus : detritus derived from the disintegration and decomposition of once-living organisms; further designated as phytodetritus or zoodetritus, depending on whether the original organism was vegetal or animal
      • analytical chemistry : chemistry that deals with analysis of different elements in a compound.
      • industrial applied chemistry :  the application of chemistry to industry and the arts
      • colloid chemistry : chemistry dealing with the nature and composition of colloids.
      • ecological chemistry : the study of those chemical compounds synthesized by plants that serve no metabolic purpose but which, by reason of their toxic effect on insects and higher animals, influence a community of interacting plants and animals.
      • medical chemistry : chemistry as it relates to medicine.
      • pharmaceutical chemistry : chemistry that deals with the composition and preparation of substances used in treatment of patients or diagnostic studies.
      • physical chemistry : the branch of chemistry that uses a quantitative approach, applying the concepts and laws of physics, to describe and understand chemical properties.
      • surface chemistry : the study of forces acting at the surfaces of gases, liquids, or solid, or the interfaces between 2 states.
      • synthetic chemistry : that branch of chemistry which deals with the building up of chemical compounds from simpler substances or from the elements.
      • geochemistry : the science concerned with study of the elements in the earth’s crust and the chemical changes that occur therein.
    • General chemistry
      • acid : any of a large class of chemical substances defined by three chemical concepts of increasing generality. An Arrhenius acid is a substance that lowers the pH (increases the hydrogen ion concentration) when added to an aqueous solution; such substances have a sour taste, turn litmus red, and react with alkalis to form salts. A Bronsted-Lowry acid is a species that acts as a proton donor in solution; e.g., the ammonium ion (NH4+) can donate a proton leaving ammonia (NH3); such species are termed conjugate acid-base pairs. A Lewis acid is a species that can accept a pair of electrons to form a covalent bond; e.g., BF3 in the reaction BF3 + NH3 => BF3NH3. Aqueous solutions of certain compounds that dissociate in solution, e.g., hydrogen chloride, are designated as acids by names beginning with hydro-, e.g., hydrochloric acid. Most other common inorganic acids are oxo acids; common organic acids include carboxylic acids, sulfonic acids, and phenols. The name of the anion formed by the removal of hydrogen from an acid (its conjugate base) and the names of salts and esters of acids are formed by removing the suffix -ic and the word acid and adding the suffix -ate, except for oxo acids ending in -ous, when the suffix is -ite. For particular acids, see the specific name.
        • binary acid / hydracid : an acid which contains only two elements, e.g., HCl
        • carboxylic acid : any acid containing the carboxyl (—COOH) group, including amino acids and fatty acids
        • conjugate acid : a chemical species that is formed from its conjugate base by addition of a proton, e.g., ammonium (NH4+) is the conjugate acid of ammonia (NH3)
        • haloid acid : an acid which contains no oxygen in the molecule, but is composed of hydrogen and a halogen element
        • hydroxy acid : an organic acid that contains an additional hydroxyl group
        • organic acid : an acid containing one or more carbon atoms, often specifically a carboxylic acid
        • inorganic acid : one containing no carbon atoms
        • monobasic acid : an acid having but one replaceable hydrogen atom and therefore yielding only one series of salts, e.g., HCl
        • oxygen acid : an acid that contains oxygen; an oxyacid
        • polybasic acid : an acid which contains two or more hydrogen atoms which may be neutralized by alkalies and replaced by organic radicals
        • sulfo-acid : an acid in which oxygen or carbon is replaced by sulfur
        • ternary acid : an acid which contains three distinct radicals
        • thio acid : one formed by replacement of an oxygen atom in an oxo acid or carboxylic acid by a sulfur atom, e.g., thiophosphoric acid (H3PSO3) or thioacetic acid (CH3COSH)
        • tribasic acid : an acid that has three replaceable hydrogen atoms
        • the world’s strongest acid, at least a million times more potent than concentrated sulphuric acid, has been made in a lab in California. Perhaps confusingly, it is also one of the least corrosive. The compound, called a carborane acid, is the first ‘superacid’ that can be stored in a bottle, say its creators. The previous record-holder, fluorosulphuric acid, is so corrosive that it would eat straight through the glass. The new acid’s gentleness is down to its remarkable chemical stability. Like all acids, it reacts with other compounds, donating a charged hydrogen atom to them. But what is left behind, although negatively charged, is so stable that it refuses to react further. It is this secondary reaction that is essential for corrosion. For example, hydrofluoric acid corrodes glass, which is composed largely of silicon dioxide, because the fluoride ion attacks the silicon as the hydrogen reacts with oxygen. The new acid, which has the formula H(CHB11Cl11), is incredibly good at donating hydrogen ions, or protons, which is how acidic strength is defined. It is over 100 trillion times more acidic than the water in your local swimming pool. But the carborane part of the molecule, which is what remains when a proton is given away, contains a cluster of 11 boron atoms and one carbon arranged into a shape called an icosahedron. This may be the most stable group of atoms that exists in chemistry, and explains why carborane acids refuse to take part in full corrosion. The joy of his work comes from simply dreaming up new chemicals. They allow the production of ‘acidified’ organic molecules. These are compounds that have had a hydrogen ion added to them, as in the case of many vitamins in over-the-counter supplements. Acidified compounds occur fleetingly in the digestion of food, petroleum refinement and drug manufacture. Carborane acids could be used to study these elusive chemicals more closely, or even help chemical industries to run their reactions more efficiently. But the researchers’ immediate goal would be less of a money-spinnerref
      • alkali : any of a class of compounds which form soluble soaps with fatty acids, turn red litmus blue, have pH values greater than 7.0, and form soluble carbonates. Essentially the hydroxides of cesium, lithium, potassium, rubidium, and sodium, they include also the carbonates of these metals and of ammonia.
      • pH = -log10[H+] = pKa - log10([AH] / [A-])
      • interactions
        • covalent interactions
        • non covalent interactions
          • ionic or electrostatic interactions (bonds form between oppositely charged residues)
          • hydrogen bonding (a hydrogen atom is shared between two electronegative atoms)
          • hydrophobic interactions (hydrophobic residues are forced together by water in order to maximize hydrogen bonding of water molecules)
          • van der Waals interactions (between outer electron clouds of 2 atoms).
      • reaction : the phenomena caused by the action of chemical agents; a chemical process in which one substance is transformed into another substance or substances
        • displacement reaction : a chemical reaction in which a reactant displaces a functional group from a substrate and becomes bound in the position formerly occupied by the leaving group
        • acid reaction : 1. one in which an acid participates.  2. a surplus of hydrogen ions in a solution or a pH below 7.0.  3. any test by which a surplus of hydrogen ions is recognized, such as the reddening of blue litmus
        • neutral reaction : the presence of an equal number of H+ and OH- ions in a solution, i.e., a pH of 7.0
        • alkaline reaction : 1. the presence in a solution of more hydroxyl ions than hydrogen ions, i.e., a pH greater than 7.0.  2. any test by which such a solution is recognized, such as the bluing of red litmus.
        • redox reaction : one in which there is transfer of electrons from an electron donor (the reducing agent) to an electron acceptor (the oxidizing agent).
        • Cannizzaro’s reaction : the reaction which certain aldehydes may undergo in concentrated alkali; one molecule of the aldehyde is reduced to the corresponding alcohol and another molecule is simultaneously oxidized to the salt of a carboxylic acid
      • the defining feature of aromatic hydrocarbon compounds is a cyclic molecular structure stabilized by the delocalization of p electrons that, according to the Hückel rule, need to total 4n + 2 (n = 1,2,…); cyclic compounds with 4n p electrons are antiaromatic and unstable. But in 1964, Heilbronner predicted on purely theoretical grounds that cyclic molecules with the topology of a Möbius band—a ring constructed by joining the ends of a rectangular strip after having given one end half a twist—should be aromatic if they contain 4n, rather than 4n + 2,  electrons. The prediction stimulated attempts to synthesize Möbius aromatic hydrocarbons, but twisted cyclic molecules are destabilized by large ring strains, with the twist also suppressing overlap of the p orbitals involved in electron delocalization and stabilization. In larger cyclic molecules, ring strain is less pronounced but the structures are very flexible and flip back to the less-strained Hückel topology. Although transition-state species, an unstable intermediate and a non-conjugated cyclic molecule, all with a Möbius topology, have been documented, a stable aromatic Möbius system has not yet been realized. Combining a ‘normal’ aromatic structure (with p orbitals orthogonal to the ring plane) and a ‘belt-like’ aromatic structure (with p orbitals within the ring plane) yields a Möbius compound stabilized by its extended  system.
      • colligative property : any of the properties of solutions that depend only on the concentration of osmotically active particles:
        • boiling point elevation
        • freezing point depression
        • osmotic pressure
        • vapor pressure lowering
      • International Union of Pure and Applied Chemistry (IUPAC)
      • International Union of Biochemistry and Molecular Biology (IUBMB)
      • PubChem contains the chemical structures of small organic molecules and information on their biological activities.
        • PubChem Substance: Search PubChem/Substance using text, e.g. substance name, keyword, synonym, external ID, formula, SID, etc.
        • PubChem Compound: Search PubChem/Compound using text terms including name, synonym, keyword, external ID, CID, formula, etc.
        • PubChem BioAssay: Search PubChem/BioActivity database using text terms such as cell name, protocol keyword, etc.
        • PubChem Structure Search: Search PubChem/Compound using chemical structure. Structure may be specified using SMILES, MOL file, molecular formula, etc.
      • The Virtual Library – Chemistry
      • The periodic table of elements and their main properties at EnvironmentalChemistry.com
      • Periodic table of the elements at ChemGlobe
      • IUPAC atomic weights and periodic table
      • Basic terminology of stereochemistry
      • Glossary of organic class names
      • Glossary of terms in physical organic chemistry
      • Hantzsch-Widman nomenclature for heteromonocyclic rings
      • Non-standard valence states (l convention)
      • Cyclic compounds with contiguous formal double bonds (d convention)
      • Fused and bridged fused ring nomenclature
      • Phane nomenclature
      • Numerical terms to 9999
      • Glossary of terms in bioinorganic chemistry
      • Nomenclature of isotopically modified compounds
      • Von Baeyer’s polyciclic compound nomenclature
      • Spiro nomenclature
      • Natural product and relative compound nomenclature
      • Radicals, ions & radical ion nomenclature
      • Glossary of medicinal chemistry terms : A-H ; I-X
      • ChemFinder
      • Acid-base indicators at Weizmann Institute
      • Tris buffer at Weizmann Institute
      • Sorensen’s table of buffer mixtures at Weizmann Institute
      • Rare Isotope Accelerator
      • Naming the chemical elements
      • Glossary of archaic chemical terms
      • mineralogy

Web resources

        :

Mineralogy Database

      • Uranium, the heaviest element found in nature, has an atomic number of 92 : atoms bigger than this are more likely to break apart spontaneously in radioactive decay, because the strong nuclear force that holds protons and neutrons together gets weaker as more particles jostle for space at the core of the atom. Also, protons have a positive charge and the more there are the greater the strain on the nucleus due to the repulsion between them. Eventually the nucleus shatters, spraying out smaller, more stable atoms. But physicists have predicted ‘islands of stability’ at atomic numbers 114, 120 and/or 126, where the protons and neutrons might be able to jostle themselves into a shape that minimises contact between the protons. That would allow the nucleus to hang together for much longer than its neighbours in the periodic table. The only way to make these heavy elements is to smash smaller atoms together at huge energies. The team of scientists from Lawrence Livermore National Laboratory in California and the Joint Institute for Nuclear Research in Dubna, Russia, fired a beam of heavy 48Ca atoms at a target made from 243Am, the radioactive metal found inside smoke detectors. The result of the collision was just four atoms of element 115, which lived for about 90 milliseconds before decaying into a second new element, 113[1]. Interestingly, the atoms of 113 survived for up to 1.2 seconds, long enough to allow you to do some interesting chemistry. The new elements have provisionally been named ununtrium (113) and ununpentium (115). The Dubna group has an extensive track record in this kind of alchemy. ‘Dubnium’ was named to commemorate the group’s creation of element 105, and it has also recorded evidence for elements 114 and 116. The discovery of element 118 was announced with great fanfare and then retracted amid accusations of scientific fraud

 

    • biological, metabolic or physiological chemistry / biochemistry : the chemistry of living organisms and of vital processes; physiological chemistry
    • Architecture of living matter biopolymers
      • Nucleic acids
      • Proteins
        • amino acid (AA) : any organic compound containing an amino (—NH2) and a carboxyl (—COOH) group. The 20 a-amino acids are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acid residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter g-aminobutyric acid, that have no relation to proteins
          • a-amino acid : one in which the amino and carboxyl groups are both attached to the same carbon atom.
          • w-amino acid : one having the amino and carboxyl groups attached to opposite ends of a carbon chain.
          • branched-chain amino acids (BCAA) : leucine, isoleucine, and valine; they are incorporated into proteins or catabolized for energy
          • essential amino acids : the 9 a-amino acids required for protein synthesis that cannot be synthesized by humans and must be obtained in the diet: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
          • excitatory amino acids : a group of nonessential amino acids that act as excitatory neurotransmitters in the central nervous system, including glutamic acid or L-glutamate, aspartic acid or L-aspartate, and the excitotoxins
          • nonessential amino acids : the eleven a-amino acids required for protein synthesis that are synthesized by humans and are not specifically required in the diet.

          Why are amino-acids left-handed ? Non-biological chemistry generally produces equal numbers of left- and right-handed molecules, called enantiomers, yet life chooses to use just one form to build proteins. One explanation is that, as the first chemical reactions of life began, a minute initial imbalance in enantiomers underwent some reaction that left them predominantly left-handed. The only example to date of such a process, reported by Kenso Soai in 1995, relies on chemistry that would be impossible in the conditions that are thought to have prevailed on the prebiotic Earth. The amplifying asymmetric autocatalysis discovered by Soai and coworkers in 1995 does not fit easily into the extensively investigated framework of organozinc alkylation of aldehydes. In that case the catalyst is a monomeric Zn chelate that functions as both Lewis acid and Lewis base, permitting the simultaneous coordination of both dialkylzinc reagent and aldehyde reactant. By contrast, the Soai reactants are rigid gamma-aminoaldehydes that cannot function as mononuclear chelates. Structural and computational evidence for a binuclear resting state is presented, and the energetics of mono-, di-, tri-, and tetrameric species accessible to the reacting system have been computed

ref

          . Another reaction that is more compatible with the conditions on the early Earth has been proposed by Suju P. Mathew in 2004. It not only generates an organic product that speeds up its own reaction, but also increases the proportion of left-handed versions of itself in the mixture. Tantalizingly, this reaction relies on an amino-acid catalyst, proline, as a source of asymmetry. Proline and the reaction product bind together to make a more effective catalyst

ref

          .

Web resources

 

        Glossary :

        • monosaccharide : carbohydrate that cannot be hydrolyzed into a simpler carbohydrate. The building block of oligosaccharides and polysaccharides. Simple monosaccharides are polyhydroxyaldehydes or polyhydroxyketones with three or more carbon atoms. Individual monosaccharides in a sugar chain are sometimes referred to as “sugar residues.”
          • aldose : a monosaccharide with an aldehyde group or potential aldehydic carbonyl group (by definition, this is the C-1 position)
          • ketose : a monosaccharide with a ketone group or a potential ketonic carbonyl group (typically at the C-2 position in natural compounds)
          • furanose : 5-membered (4 carbons and 1 oxygen, i.e., an oxygen heterocycle) ring form of a monosaccharide named after the structural similarity to the compound furan
          • pyranose : 6-membered (5 carbons and 1 oxygen, i.e, an oxygen heterocycle) ring form of a monosaccharide; the most common form found for hexoses and pentoses. The name is based on the structural similarity to the compound “pyran.”
          • amino sugar : a monosaccharide in which an alcoholic hydroxyl group is replaced by an amino group
          • deoxy sugar : a monosaccharide in which an alcoholic hydroxyl group is replaced by a hydrogen atom
        • glycosidic linkage : linkage of a monosaccharide to another residue via the anomeric hydroxyl group. The linkage generally results from the reaction of a hemiacetal with an alcohol (e.g., a hydroxyl group on another monosaccharide or amino acid) to form an acetal.
          • anomericity : the a or b configuration of the glycosidic bond of a sugar to another sugar or an aglycone
          • anomer : either of a pair of cyclic diastereoisomers of a monosaccharide or glycoside, differing only in the configuration at the reducing (anomeric) carbon atom and resulting of the ring structure (i.e., the C-1 position in a cyclic hemiacetal) from the new point of symmetry created by ring formation; they are designated a- and b- to denote position of the hydroxyl group below and above the plane of the ring, respectively
          • epimerase : an enzyme that catalyzes racemization of a chiral center in a sugar
          • epimers : 2 isomeric monosaccharides differing only in the configuration of a single chiral carbon. For example, mannose is the C-2 epimer of glucose
        • glycoside : a glycan containing at least one glycosidic linkage to another glycan or an aglycone
        • glycosidase : an enzyme that catalyzes the hydrolysis of glycosidic bonds in a glycan
          • exoglycosidase : an enzyme that cleaves a monosaccharide from the outer (nonreducing) end of an oligosaccharide, polysaccharide, or glycoconjugate
          • endoglycosidase : an enzyme that catalyzes the cleavage of an internal glycosidic linkage in an oligosaccharide or polysaccharide
        • glycosylation : the glycosyltransferase-catalyzed covalent attachment of a carbohydrate to a polypeptide, lipid, polynucleotide, carbohydrate, or other organic compound, generally catalyzed by glycosyltransferases, utilizing specific sugar nucleotide donor substrates
        • glycation : the nonenzymatic, chemical modification of proteins by addition of carbohydrate, usually through a Schiff-base reaction with the amino group of the side chain of lysine and subsequent Amadori rearrangement to give a stable conjugate
          • glycoxidation is a term used for glycation processes involving oxidation
        • hydrazinolysis : a chemical method that uses hydrazine to cleave amide bonds, e.g., the glycosylamine linkage between a sugar residue and asparagine or the acetamide bond in N-acetylhexosamines.
          • keratan sulfate : a polylactosamine [Galb1-4GlcNAcb1-3]n with sulfate esters at C-6 of GlcNAc and galactose residues, found as a side chain of a keratan sulfate proteoglycan
        • lysozyme : an endo-b-N-acetylhexosaminidase that cleaves the polysaccharide backbone of bacterial peptidoglycan
        • methylation analysis : a method for carbohydrate structure analysis based on the acid stability of methyl ethers and the acid lability of glycosidic linkages; used to determine the linkage positions of monosaccharide residues in an oligosaccharide chain
        • oligosaccharide / “sugar chains” : linear or branched chain of monosaccharides attached to one another via glycosidic linkages. The number of monosaccharide units can vary; the term polysaccharide is usually reserved for large glycans with repeating units.
            • antenna : a branch of an oligosaccharide emanating from a “core” structure
            • nonreducing terminus (nonreducing end) : outermost end of an oligosaccharide or polysaccharide chain, opposite to that of the reducing end
            • reducing terminus (reducing end) : end of a glycan that has reducing power because it is unattached to an aglycone and is thus a hemiacetal. In a glycoconjugate, reducing terminus is also used as a synonym for a potential reducing terminus, referring to the end of a glycan covalently attached to the aglycone by a glycosidic bond (i.e., it would have reducing power if it were released).
          • disaccharide
            • table sugar, sucrose, is a non-reducing disaccharide (Frub2-1aGlc)
            • N-acetyllactosamine : a disaccharide with the sequence Galb1-4GlcNAc
        • polysaccharide : glycan composed of repeating monosaccharides, generally greater than ten monosaccharide units in length.
          • homopolysaccharide : a polysaccharide composed of only one type of monosaccharide
            • polylactosamine (poly-N-acetyllactosamine). Repeating units of N-acetyllactosamines [Galb1-4GlcNAcb1-3]n , of variable length (sometimes called polyLacNAc).
            • polysialic acid : a homopolymer of sialic acids abundant in the brain and fish eggs and found on certain pathogenic bacteria.
          • heteropolysaccharide : a polysaccharide containing more than one type of monosaccharide
              • glycosaminoglycans (GAGs) : polysaccharide side-chains of proteoglycans or free complex polysaccharides composed of linear disaccharide repeating units, each composed of a …
                • hexosamine : hexose with an amino group in place of the hydroxyl group at the C-2 position. Common examples found in vertebrate glycans are the N-acetylated forms :
                  • N-acetylglucosamine (GlcNAc)
                  • N-acetylgalactosamine (GalNAc)

            … and …

                • … an hexose : a 6-carbon monosaccharide typically with an aldehyde (or potential aldehyde) at the C-1 position (aldohexose) and hydroxyl groups at all other positions. Common examples in vertebrate glycans are mannose, glucose, and galactose
                • … a hexuronic acid
                  • D-glucuronate (GlcA)
                  • L-iduronate (IdoA)

            Kinds of GAGs :

              • covalently linked to a proteoglycan core protein located primarily on the surface of cells or in the extracellular matrix (ECM)
                • keratan sulfates (KS) : (Gal b1-4 GlcNAc-6-sulfate)n
                • heparan sulfates (HS) : (GlcNAc-6-sulfate a1-4 GlcA-2-sulfate b1-4/IdoA-2-sulfate a1-4)n. Contains higher acetylated

 

                  glucosamine than heparin.

                  • heparin : a type of heparan sulfate made by mast cells that has the highest amount (higher than heparan sulfate) of iduronic acid and of N- and O-sulfate residues.
                • chondroitin sulfates (CS) :
                  • chondrotin sulfate A (CSA) / chondroitin 4-sulfate : (GalNAc-4-sulfate b1-3 GlcAb1-3)n
                  • chondroitin sulfate B (CSB) / dermatan sulfate (DS) : (GalNAc-4-sulfate b1-3 IdoAb1-3)n
                  • chondroitin sulfate C (CSC) / chondroitin 6-sulfate : (GalNAc-6-sulfate b1-3 GlcAb1-3)n
              • hyaluronan / hyaluronic acid (HA) : (GlcNAc b1-4 GlcA b1-3)n. It  is neither sulfated nor covalently linked to protein (ie not found in proteoglycans)

Mucopolysaccharide

              is an out-of-date term replaced by the term glycosaminoglycan. Still used as a group name for human disorders (

mucopolysaccharidoses

              ) involving glycosaminoglycan accumulation due to genetic deficiency in certain lysosomal enzymes. GAGs are highly negatively charged molecules, with extended conformation that imparts high viscosity to the solution. Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints. At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.
        • acetal : an organic compound derived from a hemiacetal by reaction with an alcohol. If the hemiacetal is a sugar, the acetal is a glycoside.
        • hemiacetal : a compound formed by reaction of an aldehyde with an alcohol group, as in ring closure of an aldose
        • ketal : an organic compound derived from a hemiketal by reaction with an alcohol. If the hemiketal is a sugar, the ketal is a glycoside
        • hemiketal : a compound formed by reaction of a ketone with an alcohol group, as in ring closure of a ketose
        • lectin : a protein (other than an anticarbohydrate antibody) that specifically recognizes and binds to glycans without catalyzing a modification of the glycan
          • C-type lectins (CTL) : a class of Ca2+-dependent lectins recognizable by a characteristic sequence comprising their CRDs
            • collectin : a C-type lectin with a collagen-like domain at NTD
            • selectin : a C-type lectin expressed by cells in the vasculature and bloodstream. The 3 known selectins are
              • L-selectin / CD62L (expressed by most leukocytes)
              • E-selectin / CD62E (expressed by cytokine-activated endothelial cells)
              • P-selectin / CD62P (expressed by activated endothelial cells and platelets)
            • C-type lectin-like domains (CTLDs)
          • I-type lectins : a class of lectins belonging to the Ig superfamily.
          • P-type lectins : class of lectins that recognize mannose-6-phosphate (also called M6P receptors)
          • S-type (sulfhydryl-dependent) b-galactoside-binding lectins / galectins : usually occurring in a soluble form, expressed by a wide variety of animal cell types and distinguishable by the amino acid sequence of their CRDs
          • hemagglutinin : a lectin that recognizes carbohydrates on the surface of RBCs and causes hemagglutination (aggregation)
        • glycoconjugate : a molecule in which one or more glycan units are covalently linked to a noncarbohydrate entity
            • aglycone : noncarbohydrate portion of a glycoconjugate or glycoside that is glycosidally linked to the glycan through the reducing terminal sugar
          • glycolipid : general term denoting a molecule containing a saccharide linked to a lipid aglycone
            • glycosphingolipid : glycolipid containing a glycan glycosidically attached to the primary hydroxyl group of ceramid
              • ceramide : the common lipid component of glycosphingolipids, composed of a long-chain basic alcohol (sphingosine) and an amide-linked fatty acid
                • cerebroside : a glycolipid composed of ceramide with an attached galactose (galactosylceramide) or glucose (glucosylceramide)
              • ganglioside : anionic glycosphingolipid containing one or more residues of Sia
            • glyceroglycolipids
          • glycopeptide : peptide having one or more covalently attached glycan units
          • glycoprotein : a protein with one or more covalently bound glycans
              • glycophospholipid anchor / glycosylphosphatidylinositol (GPI) anchor : a membrane anchor consisting of a glycan bridge between phosphatidylinositol and a phosphoethanolamine in amide linkage to the carboxyl terminus of a protein
              • mucin : large glycoprotein with a high content of serine, threonine, and proline residues and numerous O-linked saccharides, often occurring in clusters on the polypeptide.
              • proteoglycan : any protein with one or more covalently attached glycosaminoglycan chains.
              • N-glycan (N-linked oligosaccharide, N-linked glycan) : glycan covalently linked to an Asn residue of a polypeptide chain in the consensus sequence: -Asn-X-Ser/Thr. Unless otherwise stated, the term N-glycan is used generically in this book to denote the most common linkage region, Manb1-4GlcNAcb1-4GlcNAcb1-N-Asn.
              • O-glycan (O-linked oligosaccharide, O-linked glycan) : a glycan glycosidically linked to the hydroxyl group of the amino acids serine, threonine, tyrosine, or hydroxylysine. Unless otherwise stated, the term O-glycan is used in this book to denote the common linkage GalNAca1-O-Ser/Thr.
                • b-elimination : base-catalyzed, nonhydrolytic cleavage of an O-linked glycan attached to the hydroxyl moiety of a serine or threonine residue within a protein or peptide
            • glycoforms : different molecular forms of a glycoprotein, resulting from variable glycan structure and/or glycan attachment site occupancy
                • microheterogeneity : structural variations in the glycan at any given glycosylation site on a protein (one source of glycoforms)
              • glycotypes : cell-type-specific glycoforms of a polypeptide
          • sugar nucleotide : activated forms of monosaccharides, such as UDP-Gal, GDP-Fuc, and CMP-Sia, typically used as donor substrates by glycosyltransferases.
            • sugar nucleotide transporter : membrane-bound proteins that specifically transport sugar nucleotides from the cytosol into the lumen of intracellular organelles (e.g., the Golgi).
        • periodate oxidation : a selective chemical reaction for carbohydrates resulting in cleavage of CC bonds with vicinal hydroxyl groups. A technique useful in determining the structure of glycans.
        • polyisoprenoid : a lipid polymer composed of repeating units of the unsaturated 5-carbon isoprene unit
          • dolichol : a polyisoprenoid lipid carrier utilized during the assembly of N-glycans and GPI anchors
          • undecaprenol / bactoprenol / C55 isoprenoid

Web resources

 

  • an isopentenyl group (i.e. a C5 monomer) attached to the 6-amino group of A is found in some tRNA molecules. Lack of this isopentenyl group affects the regulatory properties of the tRNA but protein synthesis is not inhibited. In plants, isopentenyl adenosine (the free nucleoside) and its derivatives function as cytokinins – plant hormones which promote cell division.
  • terpenes are hydrocarbons found in plants. Monoterpenes are C10, diterpenes C20, triterpenes C30, etc; sesquiterpenes are C15. Responsible for flavors & odors, e.g. limonene, menthol. Other plant isoprenoids are the plant hormones giberellin and abscisic acid and the polymers rubber (unusual in being the all-cis isomer) and gutta percha (like rubber but all-trans).
  • side chains for ubiquinones and menaquinones (C40 to C50), for chlorophyll (phytyl; C20), and the side chain (farnesyl; C15) of heme a in cytochrome oxidase. Yeast mating factor from Rhodosporidium is an 11 amino acid peptide with a farnesyl cysteine group.
  • dimerization of C15 to C30 gives the hydrocarbon, squalene which is then cyclized to yield lanosterol, the first sterol precursor. Sterol synthesis requires the insertion of hydroxyl groups using molecular oxygen and is largely restricted to eukaryotes. Lanosterol is converted to cholesterol (animals), cycloartenol (plants) and ergosterol (fungi) from which all eukaryotic steroids are made. Certain cyanobacteria and methane oxidizing bacteria produce small quantities of other sterols.
  • dimerization of C20 to C40 gives carotenoids. Found in cyanobacteria and chloroplasts. Retinol is the prosthetic group of rhodopsin from mammalian eyes and also of bacteriorhodopsin, the pigment of Halobacterium purple membranes.
  • carrier lipids such as bactoprenol are a direct product of the main isoprene pathway. C55 in bacteria, longer in eukaryotes.
  • Archeaea lack fatty acids. Instead they have lipids made of glycerol ether-linked to polyisoprenoid hydrocarbon chains. Two types:

 

  • a) C20, spans half membrane, ether linked to glycerol at one end
  • b) C40, spans whole membrane, both ends ether linked to glycerols on opposite sites of membrane. Contribute to heat and acid resistance of Sulfolobus and Thermoplasma.

 

common name
systematic name
chemical abbreviation
melting point (°C)
common source
capric acid n-decanoic acid 10:0
lauric acid n-dodecanoic acid (in sodium dodecyl sulfate (SDS) 12:0 43.6 coconut
n-tridecanoic acid 13:0
myristic acid n-tetradecanoic acid 14:0 53.8 coconut and milk fat
n-pentadecanoic acid 15:0
palmitic acid n-esadecanoic acid 16:0 62.9 animal and vegetable
margaric acid n-heptadecanoic acid 17:0
stearic acid n-octadecanoic acid 18:0 69.9 animal and vegetable
arachidic acid n-eicosanoic acid 20:0 75.2 peanut oil
beenic acid n-docosanoic acid 22:0
lignoceric acid n-tetracosanoic acid 24:0 nervous tissues
cerotic acid n-esacosanoic 26:0 nervous tissues
montanic acid n-octacosanoic acid 28:0
            • unsaturated fatty acids
common name systematic name chemical abbreviation melting point (°C) common source
lauroleic acid 12:1cD9
miristoleic acid 14:1cD9
15:1cD9
palmitoleic acid cis-9-esadecenoic acid 16:1cD9 -1.5 milk fat
17:1cD9
oleic acid cis-9-octadecenoic acid 18:1cD9 14.0 animal and vegetable
elaidic acid trans-9-octadecenoic acid 18:1tD9 it does not occur naturally but can be synthesized from oleic acid
gadoleic acid 20:1cD9
brassidic acid 22:1cD9
erucic acid 22:1tD9
cetoleic acid 22:1
selacoleic or nervonic acid 24:1cD9
mellisic / triacontanoic acid
cis-9,trans-11 or rumenic acid
              • polyunsaturated fatty acids (PUFA)

                • omega-3 PUFAs (w3 or n3 PUFAs) are the precursors for the series-3 prostaglandins. These eicosanoids have anti-thrombogenic, anti-inflammatory and anti-atherogenic properties.
                  • all-cis-9,12,15-octadecatrienoic acid / a-linolenic acid (ALA) (18:3cD9,12,15; melting temperature = -30°C; found in lineseed and rubberseed)

 

D6

                    desaturase

                  • (18:4cD9,12,15,18)

 

                    ‡ elongation

                  • (20:4cD8,11,14,17)

 

D5

                    desaturase

                  • all-cis-5,8,11,14,17-eicosapentaenoic acid (EPA) (20:5cD5,8,11,14,17)

 

                    ‡ elongation

                  • docosapentaenoic acid (DPA) (22:5c)

 

                    ‡ elongation

                  • 24:5

 

D6

                    desaturase

                  • 24:6

 

b

                    -oxidation

                  • docosahexanoic acid (DHA) (22:6) found in some fish oils (salmon, sardines, pilchards and mackerel, ..). It is the precursor for series-5 leukotrienes and the series-3 thromboxanes.
                • omega-6 PUFA (w6 or n6 PUFAs) are the precursors for the -2 series prostaglandins
                  • palmitolinoleic acid (18:2cD9,12)
                  • cis,cis-9,12-octadecadienoic acid / linoleic acid (18:2cD9,12; melting temperature = -11°C; found in animal and vegetables)

 

D6

                    desaturase

                  • (Z, Z, Z)-6,9,12-octadecatrienoic acid / g-linolenic acid (GLA) (18:3D6,9,12). GLA is found naturally to varying extents in the fatty acid fraction of some plant seed oils. In evening primrose seed oil, it is present in concentrations of 7-14% of total fatty acids; in borage seed oil, 20-27%; and in blackcurrant seed oil, 15-20%. GLA is also found in some fungal sources. GLA is produced naturally in the body as the delta 6-desaturase metabolite of the essential fatty acid linoleic acid. Under certain conditions, e.g. decreased activity of the D6 desaturase enzyme, GLA may become a conditionally essential fatty acid. GLA is present naturally in the form of triacylglycerols (TAGs). The stereospecifity of GLA varies among different oil sources. GLA is concentrated in the sn-3 position of evening primrose seed oil and blackcurrant seed oil and in the sn-2 position in borage seed oil. GLA is concentrated evenly in both the sn-2 and sn-3 positions of fungal oil.

 

                    ‡ elongation

                  • dihomo-g-linolenic acid (DHLA) / eicosatrienoic acid (ETA) (20:3) is converted to PGE1

 

D5

                    desaturase

                  • arachidonic acid / all-cis-5,8,11,14-eicosatetraenoic acid (20:4cD5,8,11,14; found in lecithin and lard)

 

                    ‡ elongation

                  • 22:4c

 

                    ‡ elongation

                  • 24:4

 

D6

                    desaturase

                  • 24:5

 

b

                      -oxidation

                    • 22:5
                  • parinaric acid (18:4cD9,12,15,18)
              • branched fatty acids (if branching occurs at Cw it is named iso… acid, otherwise anteiso… acid)
              • cyclic fatty acids
                • lactobacillic acid / w-(2-n-octylcyclopropyl)-octanoic acid
              • hydroxyacids
              • aldehydoacids
                • glioxylic acid (2)
              • ketoacids
                • a-ketopropanoic acid / pyruvic acid
                • b-ketobutanoic acid / acetacetic acid
          • dicarboxylic acids
            • saturated
              • oxalic acid / etandioic acid / acetosella (2)
              • malonic acid / propandioic acid (3)
              • succinic acid / butandioic acid (4)
              • oxalacetic acid / 2-oxobutandioic (4)
              • malic acid / 2-hydroxybutandioic acid (4)
              • tartaric or uvic acid / 2,3-dihydroxybutandioic acid (4)
              • glutaric acid / pentandioic acid (5)
              • a-ketoglutaric acid / 2-oxopentandioic acid (5)
              • adipic acid / exadioic acid (6)
              • glucaric acid / 2,3,4,5-tetrahydroxyexanoic acid (6)
              • pimelic acid / heptadioic acid (7)
              • suberic acid / octadioic acid (8)
              • azelaic acid / nonedioic acid (9) (Azelex®, Finacea®) : occurring in whole grains and animal products; it has a cytotoxic effect on malignant or hyperactive melanocytes, apparently affecting their mitochondria; applied topically in the treatment of acne vulgaris
              • sebacic acid / decandioic acid (10)
              • dodecanedioic acid (12)
              • tricanedioic acid (13)
            • unsaturated
              • aliphatic
                • maleic acid / cis-2-butendioic acid (4)
                • fumaric acid / trans-2-butendioic acid (4)
                • itaconic acid / methylen-butandioic acid (5)
              • aromatic
                • phthalic acid (o-)
                • isophthalic acid (m-)
                • terephthalic acid (p-)
          • depside : one of a class of compounds which are products of the condensation of 2 or more molecules of phenolic carboxylic acids, e.g., tannic acid
          • tricarboxylic acids
            • aconitic acid (6)
            • 1-carboxyglutamate (6)
            • citric (6)
          • tetracarboxylic acids
            • ethylendiaminetetraacetic acid (EDTA)
          • oil : an unctuous, combustible substance which is liquid, or easily liquefiable, on warming, and is soluble in ether but insoluble in water. A fat that is liquid at room temperature. Such substances, depending on their origin, are classified as
            • animal oil :
            • mineral oil / heavy liquid petrolatum / liquid petrolatum / liquid paraffin / petrolatum liquidum / white mineral oil : a mixture of liquid hydrocarbons obtained from petroleum, with a specific gravity of 0.845–0.905; used as a cathartic and as a solvent and oleaginous vehicle in pharmaceutical preparations
              • light white mineral oil / light liquid paraffin or petrolatum : a mixture of liquid hydrocarbons obtained from petrolatum, with a specific gravity of 0.818–0.880; used as a vehicle for drugs and also as a laxative
            • vegetable oil :

Depending on their behavior on heating, they are classified as :

            • fixed, expressed or fatty oil : an oil that does not evaporate on warming. Such oils, consisting of a mixture of fatty acids and their esters, are classified as
              • solid (chiefly stearin)
              • semisolid (chiefly palmitin)
              • liquid (chiefly olein).

They are also classified depending on their tendency to solidify when exposed, in a thin film, to air as:

 

          • Q10 : relative increase in a reaction rate with temperature. It is expressed as the increase over a 10ºC interval
          • in general, an enzyme catalyzes only one reaction type (reaction selectivity) and operates on only one type of substrate (substrate selectivity). Substrate molecules are transformed at the same site (regioselectivity) and only one or preferentially one of chiral a substrate or of a racemate is transformed (enantioselectivity[special form of stereoselectivity]).
          • iron-sulfur metalloclusters : the kinetic stability of the simple materials present in the early earth pose obstacles for their conversion into biologically relevant molecules, a challenge that developing life forms had to overcome before they could tap into these chemical reservoirs. In modern organisms, enzymes containing iron-sulfur (Fe:S) clusters are often involved in these transformations. Hence, Fe:S clusters may have been some of the earliest cofactors in enzyme catalysis, reflecting naturally occurring chemical transformations in the prebiotic world. Several of the simpler Fe:S clusters spontaneously assemble in reductive aqueous solution from ferrous iron and sulfide, both of which were likely prevalent in the earliest Archaean environment. The underlying architectural element of Fe:S clusters is the 2Fe:2S rhomb, with Fe-S bond distances averaging between 2.2 and 2.3 A, and with Fe-S-Fe and S-Fe-S bond angles of 72° to 76° ad 104° to 106°, respectively, that are slightly distorted from planarity into a butterfly shape. The Fe sites are generally tetrahedral and are coordinated most commonly by sulfurs from inorganic sulfide and from cysteine thiol group, but other amino acid side chains have been observed to coordinate iron. The sulfides generally bridge 2 or 3 irons, although greater numbers of interactions have been noted. The 2 simplest Fe:S clusters, the [2Fe:2S] and [4Fe:4S] clusters, have versatile electrochemical properties with reduction potentials ranging from over 400 mV to below -400 mV, a range larger than for any other simple redox cofactor, and they are found in small electron transfer proteins such as ferredoxins or as part of an internal electron transfer path in larger enzymes. However, even these simple Fe:S clusters, have, in some cases, been chemically integrated as part of nonredox catalysis, such as in aconitase, where the cluster may serve as a Lewis acid : in aconitase, one corner of the [4Fe:4S] cluster is open and is readily substituted, in this case by citric acid. The open ligand-binding site presumably originates in the protein structure and is derived from the evolution of the enzyme structure and function. Another example of the adaptation of [4Fe:4S] clusters under the influence of the protein structure is that one iron can be lost with ease to form a [3Fe:4S] cluster in some ferredoxins or can even undergo metal substitution at single sites [at least under the guidance of bioinorganic chemists] to generate mixed-metal clusters. Fe:S metalloclusters found at the active sites of other enzymes, although reflecting many of the organizational principles of the simpler Fe:S clusters, have extensive elaborations that confer additional ligand-binding and catalytic properties :
            • nitrogenase, which catalyzes the reduction of dinitrogen to ammonia during the process of biological nitrogen fixation, has 2 different and unique variations on Fe:S clusters : the iron-molybdenum (FeMo)-cofactor, which is the site of substrate reduction, and the P cluster, which is a putative electron transfer center. In addition to the 7 Fe, 9 S, and 1 Mo found in the FeMo-cofactor, homocitrate coordinates to the Mo and a recently identified light atom, likley N, C, or O, is found at the center of the cofactor and completes the tetrahedral coordination environment of 6 unusual irons. The entire assemblage with 8 metals is coordinated to the protein through only 2 protein ligands (in contrast to a simple [2Fe:2S] cluster with 4 ligands). Although the binding site and reduction mechanism of dinitrogen have not been established, it is our belief that the 6 irons, not coordinated by the protein, are intimately involved in this process. The P cluster, which is thought to accept electrons from a second component protein and, in turn, to donate them to the FeMo-cofactor, is unique among the known Fe:S clusters in that it undergoes a dramatic conformational change between at least 2 oxidation states. Although these conformational changes and oxidation states are not necessarily relevant to dinitrogen reduction, they do demonstrate the versatile and dynamic properties inherent in these clusters.
            • the metabolism of CO by carbon monoxide dehydrogenase (CODH) is mediated by 1 of 2 different reaction mechanisms : the reversible oxidation of CO to form CO2, catalyzed at the C cluster, which is a Ni:Fe:S cluster; or the reversible reaction of CO with coenzyme A (CoA) and a methyl group to form acetylCoA, catalyzed at the A cluster of CODH/AcetylCoA synthases, which contains a [4Fe:4S] cluster bridged to a binuclear site involving Ni.
            • hydrogenases can catalyze the reversible reduction of protons to hydrogen and can serve to allow the use of dihydrogen as a reductant or to eliminate excess reducing power. 2 types of metal-based hydrogenases have been identified (in addition to nitrogenase, which can also reduce protons to H2):
              • the iron-only hydrogenases, with the active site H cluster composed of a [4Fe:4S] custer bridged to a binuclear iron center
              • the nickel-iron hydrogenase, with a binuclear cluster of iron and nickel in part bridged by sulfides.

Some of the earliest forms of these enzymes may have begun with the simpler clusters with low kinetic efficiency or even alternate metabolic function. For example, an early form of nitrogenase might have had only low dinitrogen reductase activity or initially might have even been a cyanide reductase or a cyanide hydrolase, providing fixed nitrogen to the organism from hydrogen cyanide in the primordial atmosphere. Under the stress of competition for depleted sources of fixed nitrogen, more efficient enzymes would have evolved, demanding the more complex metal clusters. How these more complicated structures might have arisen from the simpler Fe:S cluster is a matter of conjecture. It is apparent that in many cases (perhaps most notably for th nitrogenase FeMo-cofactor), the cluster requires additional assembly processes before incorporation by the enzyme. Hence, the evolution of an enzyme such as nitrogenase is, in fact, the coevolution of multiple components, some of which are only indirectly expressed as the enhanced activity of the more complex clusters. One clear indication that the cluster assembly process has accommodated the change from a reductive to an oxidative environment is that cells living in aerobic niches must actively seek and recover the poorly soluble ferric iron from their surroundings, and further cluster assembly entails the use of a protected sulfide in the form of the sulfide donation from cysteine

    • xenobiotic : a chemical which is not a natural component of the living organism exposed to it.
    • prebiotic chemistry : almost all discussions assume that amino acids, nucleotides, and possibly other monomers were first formed on the Earth or brought to it in comets and meteorites, and then condensed nonenzymatically to form oligomeric products. However, attempts to demonstrate plausibly prebiotic polymerization reactions have met with limited success. Carbonyl sulfide (COS), a simple volcanic gas, brings about the formation of peptides from amino acids under mild conditions in aqueous solution. Depending on the reaction conditions and additives used, exposure of a-amino acids to COS generates peptides in yields of up to 80% in minutes to hours at room temperature. What’s more, chains could be created through several different chemical processes, such as oxidation, alkylation and metal catalysisref. If similar processes occurred on the early Earth, they might have got life started towards more complex biochemistry. Today, COS makes up around 0.1% of the gas spewed out by volcanoes : it is not clear what the concentration of COS might have been in the prebiotic atmosphere > 3 billion years ago (when life is thought to have put in its first appearance), but it was probably significant. The reaction would have occurred near the gas emission, such as in lakes by volcanoes or in areas of underwater volcanic-gas emission such as deep vents
    • the biogeochemical cycles of trace metals in the oceans

 

      The phytoplankton of the oceans are responsible for about half the photosynthetic fixation of carbon (primary production) on Earth. In contrast to most land plants, which grow relatively slowly and contribute only a small percentage of their biomass to the terrestrial food chain on any given day, marine phytoplankton divide every day or every week to keep up with zooplankton grazers. To do this, they must take up from seawater – along with carbon, nitrogen, phosphorus, and silicon (for diatoms) – a suite of essential micronutrients that are present at trace concentrations (< 0.1

m

      M). To make matters worse, these organisms impoverish their own milieu because the elements they require for growth are continuously exported out of the sunlit surface as settling organic biomass. In comparison, terrestrial plants, which can acquire nutrients from soil and recycled litter, have a bountiful life. With regard to essential micronutrients, the ocean, particularly far from land, is the most extreme environment for life on Earth. 12 elements with atomic mass > 50 are knwon to have a biological role, often as cofactors of part of cofactors in enzymes and as structural elements in proteins. Of those, the trace metals – Mn, Fe, Co, Ni, Cu, Zn, and Cd – have been best studied by oceanographers. and are the focus of our discussion. They are present in the plankton biomass at concentrations ranging from about 50

m

      mol/mol C (1000

m

      m) for Fe, which is used in a number of the electron transfer intermediates and a host of enzymes, down to 2 mmol/mol C (30 mM) for Co, whose biochemical functions in planktonic organisms are not yet completely understood. Although enriched in rocks and soil, the concentrations of these metals are kept low in the sea by virtue of their limited solubilities and effective removal from the water column, particularly in estuaries. As a result, their concentrations fall precipitously within short distances of the coastline. Long-range atmospheric transport through aeolian dust represents an important source only for Fe, Mn, and possibly Co, which are relatively enriched in crustal material. As a result of the uptake by plankton, most essential trace metals (with the notable exception of Mn) are depleted at the surface, as exemplified by the concentration profiles of Fe ans Zn in the water column of the north Pacific Ocean. Such concentration profiles are characteristic of many algal nutrients and result from the steady downward flux of settling biomass originating chiefly from the larger phytoplankton, such as diatoms and cocolithophorids, often packagede in the feces of zooplankton. This downward flux is balanced by a slow upward advective/diffusive flux of dissolved elements remineralized at depth by heterotrophic bacteria. Much of the organic matter, including most of what is produced by the picoplankton (< 2 mm diameter), is remineralized at the surface. Essential elements are thus recycled  rapidly through the biota at the surface and more slowly during vertical transport in most areas of the ocean that the surface concentrations are only a small fraction of those in the deep: most are present at concentrations between pM and nM, about one-millionth of the celular concentration in the plankton itself. By pushing electrochemical methods to the limt, it has been demostrated that the bulk of the dissolved concentrations of several metals – Fe, Co, Cu, Zn, and Cd – are present in nonreactive forms at the ocean suface. This absence of reactivity is prima facie evidence that the metals are bound to some strong unknown ligands. A fraction of the metal that is measured as dissolved (< 0.4 mm filter) may be colloidal. There is good reason to believe that strong metal chelators may be present in surface seawater, because cultured marine microorganisms release such chelators in their growth medium. The best documented case is the production of siderophores by marine bacteria. Some of these siderophores have been characterized and found to contain the usual hydroxamate and catechol functionalities. Some siderophores have fatty acid tails of variable length and a head group that contains one

a

      -hydroxy acid in addition to hydroxamates. The hydrophobic nature of these siderophores gives a tantalizing clue about their likely mode of action in the oceans. Further, the cleavage of both the hydrophobic tail and the

a

      -hydroxy acid group upon illumination may be important in enhancing the diurnal redox cycle of Fe in surface seawater. Hydroxamate and catechol functionalities have indeed been identified in the dissolved organic matter in seawater. Further, the rapid loss of reactivity of the Fe added to some ocean ecosystem argues strongly for a microbial source of Fe chelators. Both prokaryotic and eukaryotic phytoplankton species also release strong Cu and Cd complexing agents in cultures when exposed to high concentrations of these metals. These agents presumably serve to detoxify the metals, for it appears that the complexes are exported from the cells: Cd phytochelatin complexes [chiefly (

g

      -Glu-Cys)2-Gly-Cd] from diatoms; novel peptide complexes of Cu [Gln-Cys-Cu(I) and Arg-Cys-Cu(I)] from coccolithophores; and unkwnown Cu-complexing agents from the cyanobacterium Synechococcus. So far, no ligand specialized in the uptake rather than the detoxification of metals other than Fe has been characterized. Cyanobacteria appear to release a cobalophore, whose function in Co uptake and sequestration is similar to that of siderophores for Fe. There are biogenic sources for the putative seawater chelators of Fe, Cu, Cd, and Co, even if some of these have only been observed to be produced at relatively high metal concentrations in cultures. Notably asbsent so far is any laboratory evidence for the production of chelators of Zn, one of the most tightly bound trace metals in surface seawater according to electrochemical data. Nonetheless, a reasonably prudent working hypothesis is that the dissolved Fe, Cu, Zn, Cd, and Co in seawater is doimated by organic complexes – some with low molecular mass ligands produced specifically for metal transport, sequestration, or detoxification; some in high molecular mass ligands produced specifically for metal transport, sequestration, or detoxification; some in high molecular mass compounds (presumably, proteinaceous material in the process of decomposition) – which may exchange the metals more or less readily and may be separable as collodial material. In addition to being the object of competitive binding by biogenic ligands, th etrace metals that can attain more than one oxidation state in seawater – Fe, Mn, Cu, and Co – are also subjected to a dynamic redox cycle. This cycle is directly or indirectly powered in part by photochemistry. Absorption of light in the high visible-low ultraviolet range promotes charge-transfer reactions in many complexes of Fe(III) and Cu(II), including those at the surface of solids. Often the reduced metal is then released from the oxidized ligand. Metals can also be subjected to reduction (and oxidation) by O

2-

      derived from photolysis of organic matter. The photochemical reduction of Mn(IV) oxides to soluble Mn(II) results in the atypical maximum in dissolved Mn concentration observed at the surface. The planktonic biota is also active in promoting redox transformations of metals. Diatoms are known to reduce Fe(III) extracellularly from complexes such as siderophores through an uncharacterized and possibly indirect enzymatic pathway. This reduction allows the organisms to access a pool of Fe that would otherwise be unavailable. Fe(II) uptake involves reoxidation by a Cu-dependent oxidase at the cell surface. Manganese presents the best documented case of microbially mediated redox transformation in seawater. Mn(II) is oxidized by a number of bacteria and bacterial spores via an extracellular multicopper oxidase. The function of this oxidation, which results in the formation of a solid Mn oxide casing around the organism, is unknown, although it has been speculated that it might be a way to bring oxidative power into reducing sediments upon settling of the resting cells or spores. The picture that emerges is one of an extremely dynamic trafficking in essential trace metals in surface seawater. Some organisms are taking up metals, some are sequestering them for their own use, and some are binding them in nontoxic forms. Some organisms are chelating metals; others are prying them loose from chelators. Some organisms are reducing metals; others are oxidizing them. All this activity suggests that these trace metals matter greatly to the plankton in the sea, which raises the question of what role they play in the growth of microorganisms and their cycling of major nutrients. Historically, the question of what limits the productivity of the oceans has been debated among N and P partisans with respect to the areas of the oceans affected and the temporal and spatial scales involved. But over the past dozen years, Fe has also become recognized as a prime limiting element. In experiments of various scales and durations, addition of N, P, of Fe has been shown to increase the rate of photosynthesis in samples of surface waters from various parts of the world. But this is perhaps too simplicistic a view: these additions do not accelerate equally the growth of all phytoplankton taxa, and the acquisition of major nutrients is not independent of the availability of trace metals that catalyze their transformations. For example, the dearth of Fe that has been shown to limit primary production in the Equatorial Pacific inhibits diatom growth most effectively. By virtue of their large size, these phytoplankton have more difficulty than smaller ones in acquiring nutrients fast enough to maintain rapid growth. Unlike picoplankton, they cannot grow on the low ambient NH

4+

      concentration and must instead rely on NO

3-

      , whose reduction to NH

4+

      before assimilation requires Fe both as a cofactor in the reductases and for photosynthetic production of reductants. Diatoms thus need relatively more Fe and are less able to take it up. In an enviroment characterized by very low concentrations of trace metals, the acquisition and transformation of major nutrients may often be limited at both cellular and ecosystem levels by the activity of key metalloenzymes. The most pervasive effect of low trace metal concentrations on the productivity and ecology of the oceans is probably the Fe limitation of N

2

      fixation, which requires the metal in nitrogenase and additional energy and reducing power. Although firm experimental evidence showing  limitation of nitrogenase activity in the field is lacking, laboratory data shown that

Trichodesmium

      - a major N

2

      fixer – requires 5 times as much Fe per C when grown on N2 than when grown on NH

4+

      . Such data, coupled with models of the iron budget of the world ocean, predict widespread Fe limitation of N

2

      fixation. Because all nitrogen transformation involve metalloenzymes, it is possible that low metal availability also limits other critical steps in the nitrogen cycle. For example, low Cu availability in oxygen minimum zones has been hypothesized  to be responsible for the release of N

2

      O to the atmosphere as a result of low nitrous oxide reductase activity. Low Fe may also inhibit nitrate reductase actrivities both in the assimilatory pathway of phytoplankton (as mentioned above for diatoms) and in the dissimilatory pathway of denitrifiers. Low concentrations of Ni, a cofactor in urease, may limit the ability of plankton to assimilate urea, a quantitatively important source of nitrogen. In addition to influencing the carbon cycle indirectly thorugh their effects on the nitrogen cycle, trace metals have a direct effect on photosynthesis and respiration at the cellular and ecosystem levels. The low productivity in Fe-depleted regions of the oceans is primarily due to the low efficiency of the light reaction of photosynthesis, which requires a host of Fe-containig electron transfer intermediates. Electron transfer in respiration also becomes inefficient at low Fe, and heterotrophic bacteria then convert less of the C they consume into biomass. By itself, the dark reaction of photosynthesis (the Calvin cycle) does not require trace metals, but the acquisition of inorganic carbon does. Because of the low affinity (Ks = 20 to 100 mm) of the enzyme ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) for CO

2

      (and the competition by O

2

      ), the CO

2

      concentration at the site of fixation must be increased above its concentration in seawater (10 mm). In all marine phytoplankton, the

carbon-concentrating mechanism (CCM)

      involves the Zn metalloenzyme carbonic anhydrase, which catalyzes the equilibrium between HCO

3-

      and CO

2

      . In some taxa, carbonic anhydrase can function with Co or Cd as a metal center. Thus, the acquisition of CO

2

      depends in part on the availability of Zn, Co, and Cd, particularly under conditions of low

p

      CO

2

      . This new understanding, along with fundamental questions regarding the mechanisms of the CCM in various taxa, is resulting in a resurgence of interest in the role of CO

2

      availability in controlling the growth of marine phytoplankton and the assemblage of phytoplankton species in the sea. The replacement of one essential element by another may be a common occurrence in marine plankton, as suggested in some growth experiments. For example, the replacement of Zn by Cd and Co observed in carbonic anhdrase may also occur in other Zn metalloenzymes such as aklkaline phosphatase, which allows phytoplantonn to acquire P from organic compounds. Metal substitution may explain some low metal requirement observed in open-ocean species. For example, oceanic diatoms that have extremely low Fe requirements are easily limited by Cu and may have replaced Fe with Cu ion some critical biochemical functions. In contrast, ambient Cu concentrations are toxic to some cyanobacteria, perhaps as a result of nonfunctional Cu substitution for essential metals. Hence, the growth of cyanobacteria depends on the presence of sufficient Cu-chelating agents, and the modulation of Cu chelation by various microorganisms may represent a continual battle betwen those that need to acquire copper and those that need to repress its toxicity. Although planktonic microorganisms control the chemistry and cycling of biologically important trace metals in the sea, the metals control in part the growth of the organisms and their cycling of major nutrients such as C and N. This mutual interaction results from the complex coevolution of planktonic life and ocean chemistry. The pradoxical result is a maintenance of biological productivity in an environment impoverished in essential elements. The concentrations of some trace metals in surface seawater are so low that the kinetics of metal uptake by phytoplankton in the sea are reaching the limits posed by diffusion and by the kinetics of binding to transport ligands at the surface of cells. It also seems that the metalloenzymes of marine microorganisms often have unusual metal centers : any metal that can used in a particular biological function may actually be used that  way by some marine organisms. The biogeochemical cycle of trace metals in the oceans may thus have reached the limit of what is physically, chemically, and biochemically possible.