Flavin-dependent dehydrogenase

Step 6 A Flavin-Dependent Dehydrogenase (Reaction, structure)... 

A convenient way to summarize the reactions of coenzyme A thioesters is by reviewing the )3-oxidation pathway for fatty adds". Fatty acid activation occurs by acylation of the coenzyme A thiol by way of an acyl adenylate. This is then dehydrogenated to an o,/3-enoyl acyl coenzyme A derivative by a flavin-dependent dehydrogenase. The ability of the adjacent carbonyl to provide resonance stabilization of the product appears to be an important aspect of this reaction. Such flavin-dependent dehydro- nations occur in other reaction sequences, but only where carbonyl resonance stabilization is possible. Water adds to the a,j8-enoyl thioester to generate a j8-hydroxy fatty acid derivative, a reaction facilitated by j8-carbonium ion stabilization in enoyl thioesters. The j3-hydroxyl is next... 

Other metabolic enzymes that show polymorphic differences in that they can occur as genetic high-activity and low-activity variants include acetylcholinesterase, butyrylcholinesterases, flavin-dependent monooxygenase, alcohol dehydrogenase, epoxide hydrolase, and arylesterase (Beltoft et al. 2001). 

A flavin-dependent formate dehydrogenase system found in Methanobacterium passes electrons from dehydrogenation of formate to FAD and then to the deazaflavin coenzyme F q.673 In contrast to these Mo-containing enzymes, the formate dehydrogenase from Pseudomonas oxalaticus, which oxidizes formate with NAD+ (Eq. 16-66), contains neither Mo or Se.674... 

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. 

Quinoproteins constitute a class of dehydrogenases distinct from the nicotinamide-and flavin-dependent oxidoreductases 11691. They use different quinone cofactors to convert a vast variety of alcohols and amines into their corresponding carbonyl products11701. Proteins containing the cofactor pyrroloquinoline quinone (PQQ) (Fig. 16.2-36) form the largest and best-characterized sub-group. 

Similarly to the flavin-dependent reactions, several mechanisms have been discussed, including covalent substrate-PQQ intermediates or hydride transfer1179-1811. The most important QDHs are methanol (alcohol) dehydrogenase (E.C. 1.1.99.8) and glucose dehydrogenase (E. C. 1.1.99.17), which will be discussed briefly. 

Flavin-dependent oxidases and dehydrogenases mediate the net two-electron oxidation of their respective substrates with the formation of a reduced flavin intermediate. In a subsequm oxidative half-reaction, oxidases transfer two electrons to molecular oxygen, whereas dehydrogenases utilize one-electron red-... 

The oxidation reactions involved are catalyzed by a series of nicotinamide adenine dinucleotide (NAD+) or flavin adenine dinucleotide (FAD) dependent dehydrogenases in the highly conserved metabolic pathways of glycolysis, fatty acid oxidation and the tricarboxylic acid cycle, the latter two of which are localized to the mitochondrion, as is the bulk of coupled ATP synthesis. Reoxidation of the reduced cofactors (NADH and FADH2) requires molecular oxygen and is carried out by protein complexes integral to the inner mitochondrial membrane, collectively known as the respiratory, electron transport, or cytochrome, chain. Ubiquinone (UQ), and the small soluble protein cytochrome c, act as carriers of electrons between the complexes (Fig. 13.1.1). 

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