Coenzyme-dependent reactions

Carbon-carbon bond formation and cleavage are reactions in which coenzymes play a major role. The coenzymes as a group possess functionality that is not normally found in the side chain of a protein and thus can provide for chemical mechanisms that are not accessible in a protein without such a cofactor. The coenzyme-dependent reactions follow distinct mechanistic patterns and operate... 

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

Loftier F, R Muller, F Lingens (1991) Dehalogenation of 4-chlorobenzoate by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3 an ATP/coenzyme A dependent reaction. Biochem Biophys Res Commun 176 1106-1111. 

N-Hydroxy arylamines are also converted to N-acetoxy arylamines (V), but apparently by an acetyl coenzyme A-dependent enzymatic O-esterification (7, 8). Similarly, N-sulfonyloxy arylamines (VI) are thought to arise by a PAPS-dependent enzymatic O-sulfonylation of N-hydroxy arylamines (9,10) while 0-seryl or 0-prolyl esters (VII) are formed by their corresponding aminoacyl tRNA synthetases in a ATP-dependent reaction (11,12). 

Mechanistically, transamination by the free coenzyme proceeds through a number of discrete steps as illustrated in Fig. 3. The first step of the process, aldi-mine formation (Fig. 3, Step I), is common to all pyridoxal-dependent reactions. The rate and extent of this reaction are influenced by factors including reactant concentrations, the nature of the amino acid, pH, and solvent. However, it is important to realize that the coenzyme itself facilitates Schiff base formation in... 

Vitamin Be is again a small family of related compounds having the same biological activity. These include pyridoxine, pyridoxai, and pyridoxamine. In humans, these molecules are readily interconverted, accounting for their equivalence as vitamins. The stuff in your vitamin pill is likely to be pyridoxine. The actual molecule that functions as a coenzyme in metabolism is pyridoxai phosphate, in which a phosphate group has been added to pyridoxai in an ATP-dependent reaction. 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

The number of vitamin B 12-dependent reactions is not large. Most of these involve rearrangements of the carbon skeletons of metabolites. Such reactions are important in linking some aspects of fatty acid metabolism to the citric acid cycle. In another form, a vitamin Bi2-derived coenzyme is involved, along with folic acid coenzymes, in the metabolism of one-carbon fragments, including the biosynthesis of methionine. 

Vitamin B12 coenzyme 864. See also Cobalamin dependent reactions, table 871 enzymatic functions 870 - 877 isomerization reactions 872 nonenzymatic cleavage 870 ribonucleotide reductase 871 Vitamin B6 family 721, 738... 

Propylene glycol is metabolized by several aerobic bacteria to acetoacetate, which can be catabolized as an energy source (see references 509a and 509b). The first step is conversion to an epoxide which reacts further in coenzyme M-dependent and C02-dependent reactions to form acetoacetate. Can you propose chemical mechanisms ... 

L-Serine is converted to pyruvate + NH3 by serine dehydratase (deaminase) in a PLP-dependent reaction. However, using the same coenzyme selenocysteine is converted by selenocysteine lyase into L-alanine + elemental selenium Se°. l-Cysteine may be converted by PLP-dependent enzymes into wither H2S or into S° for transfer into metal clusters. Compare the chemical mecha-... 

Structures of catalytic intermediates in pyridoxal-phosphate-dependent reactions. The initial aldimine intermediate resulting from Schiff s base formation between the coenzyme and the a-amino group of an amino acid (a). This aldimine is converted to the resonance-stabilized... 

Flavins are very versatile redox coenzymes. Flavopro-teins are dehydrogenases, oxidases, and oxygenases that catalyze a variety of reactions on an equal variety of substrate types. Since these classes of enzymes do not consist exclusively of flavoproteins, it is difficult to define catalytic specificity for flavins. Biological electron acceptors and donors in flavin-mediated reactions can be two-electron acceptors, such as NAD+ or NADP+, or a variety of one-electron acceptor systems, such as cytochromes (Fe2+/ Fe3+) and quinones, and molecular oxygen is an electron acceptor for flavoprotein oxidases as well as the source of oxygen for oxygenases. The only obviously common aspect of flavin-dependent reactions is that all are redox reactions. 

Vitamin B12 is required by only two enzymes in human metabolism methionine synthetase and L-methylmalonyl-CoA mutase. Methionine synthetase has an absolute requirement for methylcobalamin and catalyzes the conversion of homocysteine to methionine (Fig. 28-5). 5-Methyltetrahydrofolate is converted to tetrahydrofolate (THF) in this reaction. This vitamin B12-catalyzed reaction is the only means by which THF can be regenerated from 5-methyltetrahydrofolate in humans. Therefore, in vitamin B12 deficiency, folic acid can become trapped in the 5-methyltetrahydrofolate form, and THF is then unavailable for conversion to other coenzyme forms required for purine, pyrimidine, and amino acid synthesis (Fig. 28-6). All folate-dependent reactions are impaired in vitamin B12 deficiency, resulting in indistinguishable hematological abnormalities in both folate and vitamin B12 deficiencies. 

Equation 21 depicts the reaction of the simplest NAD+/NADH-dependent enzyme, alcohol dehydrogenase153. This enzyme performs the last reaction in ethanol fermentation. Indicated in the equation is the fundamental finding on such reactions first reported by Westheimer, Vennesland and coworkers154-157. The hydrogen transfer is not only direct in both directions (as opposed to solvent-mediated), but is totally stereospecific in both directions for both the coenzyme and the substrate. The pro-R hydrogen is transferred from both the coenzyme and the substrate ethanol. This was an observation of enormous implications for NAD+-dependent reactions, in particular, and enzyme catalyzed reactions, in general, that has been borne out by literally hundreds of examples. 

Because of the central role of flavin coenzymes in energy-yielding metabolism, reference intakes are sometimes calculated on the basis of energy intake 0.6 to 0.8 mg per 1,000 kcal (0.14 to 0.19 mg per MJ). However, in view of the wide range of riboflavin-dependent reactions, in addition to energy-yielding metabolism, it is difficult to justify this basis for the calculation of requirements. 

Steady-state kinetic analysis shows that biotin-dependent reactions proceed by way of a two-site ping-pong mechanism the two-part reactions are catalyzed at distinct sites in the enzyme. These sites may be on the same or different polypeptide chains in different biotin-dependent enzymes. The e-amino linkage of lysine to the side chain of biotin in biocytin allows considerable movement of the coenzyme - the distance from C-2 of lysine to C-5 of biotin is IdA, thus allowing movement of biotin between the carboxylation and carboxyltransfer sites. 

Frey, P. A., Essenberg, M. K., and Abeles, R. H., 1967, Studies on the mechanism of hydrogen transfer in the cobamide coenzyme-dependent dioldehydrase reaction. J. Biol. Chem. 242 5369n5377. 

The coenzyme that mediates this transfer of a methyl group is methylcobalamin, derived from vitamin Bj2- In fact, this reaction and the rearrangement of 1-methylmalonyl CoA to succinyl CoA (Section 23.5.4), catalyzed by a homologous enzyme, are the only two Bj2-dependent reactions known to take place in mammals. Another enzyme that converts homocysteine into methionine without vitamin Bj2 also is present in many organisms. 

The proposed catalytic mechanism of the ferredoxin oxidoreductase [32] is shown in Fig. 4, a similar mechanism existing for the analogous citric acid cycle enzyme, 2-oxoglutarate oxidoreductase. In outline, the 2-oxoacid is decarboxylated in a TPP-dependent reaction to give an hydroxyalkyl-TPP. From this, one electron is abstracted and transferred to the enzyme-bound iron-sulphur cluster, generating a free-radical-TPP species. This intermediate can then interact direct with coenzyme-A to form acyl-CoA, the iron-cluster receiving the second electron. In each case, ferredoxin serves to re-oxidise the enzyme s redox centre. 

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