Coenzyme functions

Imperiali B, McDonnell KA, Shogren-Knaak M (1999) Design and Construction of Novel Peptides and Proteins by Tailored Incorparation of Coenzyme Functionality. 202 1-38 Ito S, see Yoshifuji M (2003) 223 67-89... 

NAD and NADP and FMN and FAD, respectively. Pantothenic acid is a component of the acyl group carrier coenzyme A. As its pyrophosphate, thiamin participates in decarboxylation of a-keto acids and folic acid and cobamide coenzymes function in one-carbon metabolism. 

The clinical significance of thiamine and its necessity for pyruvic acid oxidation has been discussed. Recent reports concerning the coenzyme function of thiamine in pentose (H13), tryptophan (D2), and lipoic acid metabolism (R6) have increased our knowledge of thiamine in metabolism and lend added interest to the role of thiamine in clinical problems. This method has also been used to assay thiamine in liver and brain. 

Powerful mechanistic enzymology in conjunction with structural biology studies have provided insight into the manner in which the protein environment of an apoenzyme augments and controls coenzyme reactivity. The goal of the protein design efforts that include coenzyme functionality is to estabhsh whether these features can be emulated within designed peptide and protein constructs. 

The complexity of the environment surrounding the coenzyme has prevented most simple model systems from dramatically enhancing thiamine reactivity or specificity [46-48]. Peptide- or protein-based models have the advantage of presenting a reasonably complex environment to the coenzyme functionality within a water soluble, yet synthetically accessible, scaffold. 

Modeling Flavin Coenzyme Function in Peptides and Proteins... 

Modeling Nicotinamide Coenzyme Function in Protein and Peptide Systems... 

These authors point out that these results emphasize the difficulty in achieving specific function with this system and highlight the necessity for very precise interactions between the coenzyme functionality and its environment to control and augment reactivity. Peptidyl systems may offer more control over the coenzyme environment as they are readily synthetically accessible and easily manipulated. However, generating stable peptidyl structures presents a significant design challenge. 

Significant advances have been made in the preparation of discrete macromolecules that include both coenzyme function and a defined polypeptide or protein architecture. Preliminary, but promising, functional studies have been carried out and assay methods developed. While in many cases rather modest effects have been observed, what is significant is that the methodology exists to prepare, characterize, and study defined macromolecular constructs. With new information becoming available on co enzyme-dependent protein catalysts from structural biology and mechanistic enzymology, it should be possible to more fully exploit the remarkable breadth of coenzyme reactivity in tailored synthetic systems. 

The nucleoside phosphates (1) are not only precursors for nucleic acid biosynthesis many of them also have coenzyme functions. They serve for energy conservation, and as a result... 

The chemistry of a fourth coenzyme was at least partially elucidated in the period under discussion. F. Lynen and coworkers treated P-methylcrotonyl coenzyme A (CoA) carboxylase with bicarbonate labelled with 14C, and discovered that one atom of radiocarbon was incorporated per molecule of enzyme. They postulated that an intermediate was formed between the enzyme and C02, in which the biotin of the enzyme had become car-boxylated. The carboxylated enzyme could transfer its radiolabelled carbon dioxide to methylcrotonyl CoA more interestingly, they found that the enzyme-COz compound would also transfer radiolabelled carbon dioxide to free biotin. The resulting compound, carboxybiotin [4], was quite unstable, but could be stabilized by treatment with diazomethane to yield the methyl ester of N-carboxymethylbiotin (7) (Lynen et al., 1959). The identification of this radiolabelled compound demonstrated that the unstable material is N-carboxybiotin itself, which readily decarboxylates esterification prevents this reaction, and allows the isolation and identification of the product. Lynen et al. then postulated that the structure of the enzyme-C02 compound was essentially the same as that of the product they had isolated from the reaction with free biotin, but where the carbon dioxide was inserted into the bound biotin of the enzyme (Lynen et al., 1961). Although these discoveries still leave significant questions to be answered as to the detailed mechanism of the carboxylation reactions in which biotin participates as coenzyme, they provide a start toward elucidating the way in which the coenzyme functions. 

Notice that in the overall reaction there is no net production or consumption of NAD+ or NADH the coenzymes function catalytically and are recycled repeatedly without a net change in the concentration of NAD+ + NADH... 

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