Dehydrogenases nucleotide

Gofactors. Frequendy proteins exist in their native state in association with other nonprotein molecules or cofactors, which are cmcial to their function. These may be simple metal ions, such as Fe " in hemerythrin or Ca " in calmodulin a heme group, as for the globins nucleotides, as for dehydrogenases, etc. 

In contrast to the nicotinamide nucleotide dehydrogenases, the prosthetic groups FMN and FAD are firmly associated with the proteins, and the flavin groups are usually only separated from the apoen2yme (protein) by acid treatment in water. However, in several covalently bound flavoproteins, the enzyme and flavin coen2ymes are covalently affixed. In these cases, the flavin groups are isolated after the proteolytic digestion of the flavoproteins. 

FIGURE 18.10 Hydrogen and electrons released in the course of oxidative catabolism are transferred as hydride ions to the pyridine nucleotide, NAD, to form NADH -t- H in dehydrogenase reactions of the type... 

Inosine monophosphate dehydrogenase (EVDPDH) is a key enzyme of purine nucleotide biosynthesis. Purine synthesis in lymphocytes exclusively depends on the de novo synthesis, whereas other cells can generate purines via the so-called salvage pathway. Therefore, IMPDH inhibitors preferentially suppress DNA synthesis in activated lymphocytes. 

Inosine monophosphate dehydrogenase (IMPDH) is the key enzyme of purine nucleotide biosynthesis. Proliferation of activated lymphocytes dq ends on rapid de novo production of purine nucleotides for DNA synthesis. 

The fact that adenosine and its derivatives are azo coupling components is used for immobilizing nicotinamide-adenine nucleotide (NAD+) for affinity chromatography purposes. In 12.58 NAD+ is bonded to a matrix through an azo bond. Compound 12.58 is used for the purification of dehydrogenase enzymes (Hocking and Harris, 1973). 

The carbon monoxide dehydrogenase of the aerobe Oligotropha carboxidovorans contains both Cu and Mo in the form of a cluster in which the Mo is bound to the thiol groups of molybdopterin cytosine nucleotide, and the Cu to cysteine residue in the form of a Cu-S-Mo(=0)OFl cluster (Dobbek et al. 2002). 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

H7. Hirono, A., and Beutler, E., Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(-). Proc. Natl. Acad. Sci. U.S.A. 85,3951-3954 (1988). 

T7, Takizawa, T., Yoneyama, Y., Miwa, S and Yoshida, A., A single nucleotide base transition is the basis of the common human glucose-6-phosphate dehydrogenase variant A(+). Genomics 1,228-231 (1987). 

Alcohol dehydrogenases catalyze oxidation of alcohols in a reaction dependent on the pyridine nucleotide NAD+ [Eq. (5)]. Since the reaction is reversible, alcohol dehydrogenases also catalyze the reduction of aldehydes by... 

The carbonyl reductases catalyze reduction of aldehydes and ketones by reduced pyridine nucleotides (NADH and/or NADPH). As mentioned earlier, alcohol dehydrogenase can perform this function in the presence of a high ratio of NADH to NAD+. Other enzymes capable of carbonyl reduction include the aldehyde and ketone reductases. The aldehyde and ketone reductases have a ubiquitous species distribution, with the enzymes present in organisms ranging from bacteria to vertebrates. The mammalian carbonyl reductases have been extensively reviewed (101). 

The antagonists of nicotinic acid are 6-aminonicotinamide and, less potent, 3-acetylpyridine and pyridine-3-sulfonic acid (H15, J4). Nicotinamide has also been reported to be effective in experimental cancer (S3). It is supposedly converted to nonphysiological nucleotide analogs of NAD and NADP because it becomes attached to available apo-dehydrogenase the resulting enzyme cannot function in hydrogen and electron-transfer reactions essential to normal cellular metabolism (D7). 

Fig. 1. General scheme of the hydrogen transfer as catalyzed by dehydrogenase reactions. R represents the residue of the pyridine nucleotide molecule.

Both the enzymes were prepared by a special technique from the insoluble portion of guinea pig liver mitochondria, and they are quite specific with respect to the requirement of pyridine nucleotide (H9, Hll). However, dehydrogenases catalyzing reaction (25) with NAD as coenzyme have been reported (Mil, S13, T3), thus confirming the importance of the source of the enzyme and the purification procedure employed. 

H10. Hochster, R. M., Pyridine nucleotide specificities and rates of formation of G-0-P and of 0-PG dehydrogenases in Aspergillus flavus-oryzae. Arch. Biochem. Biophys. 60, 499-501 (1957). 

R8. Rees, E. D., and Huggins, C., Steroid influences on respiration, glycolysis and levels of pyridine nucleotide linked dehydrogenases of experimental mammary cancers. Cancer Research 20, 963-971 (1960). 

---