Prosthetic group flavoprotein

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. 

All these intermediates except for cytochrome c are membrane-associated (either in the mitochondrial inner membrane of eukaryotes or in the plasma membrane of prokaryotes). All three types of proteins involved in this chain— flavoproteins, cytochromes, and iron-sulfur proteins—possess electron-transferring prosthetic groups. 

Similarly, the reduction of riboflavin prosthetic groups (FP) of some flavoprotein dehydrogenases may also involve a free radical intermediate. 

Flavoprotein enzymes contain flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) as prosthetic groups. FMN and FAD are formed in the body from the vitamin riboflavin (Chapter 45). FMN and FAD are usually tighdy—but not covalendy—bound to their respecdve apoenzyme proteins. Metalloflavopro-teins contain one or more metals as essential cofactors. 

Br Riboflavin Coenzyme in oxidation and reduction reactions prosthetic group of flavoproteins Lesions of corner of mouth, lips, and tongue seborrheic dermatitis... 

Figure 9.1 CYP catalytic cycle. The sequential two-electron reduction of CYP and the various transient intermediates were first described in the late 1960s [206], The sequence of events that make up the CYP catalytic cycle is shown. The simplified CYP cycle begins with heme iron in the ferric state. In step (i), the substrate (R—H) binds to the enzyme, somewhere nearthe distal region of the heme group and disrupts the water lattice within the enzymes active site [207], The loss of water elicits a change in the heme iron spin state (from low spin to high spin) [208]. Step (ii) involves the transfers of an electron from NADPH via the accessory flavoprotein NADPH-CYP reductase, with the electron flow going from the reductase prosthetic group FAD to FMN to the CYP enzyme [206,209]. The...

Many of the amino acids originally tested by Krebs were racemic mixtures. When naturally occurring L-amino acids became available the oxidase was found to be sterically restricted to the unnatural, D series. [D-serine occurs in worms free and as D-phosphoryl lombricine (Ennor, 1959)]. It could not therefore be the enzyme used in the liver to release NH3 in amino acid metabolism. D-amino acid oxidase was shown by Warburg and Christian (1938) to be a flavoprotein with FAD as its prosthetic group. A few years later Green found an L-amino acid oxidase in liver. It was however limited in its specificity for amino acid substrates and not very active—characteristics which again precluded its central role in deamination. 

The cases of myoglobin and hemoglobin are not rare. Many enzymes are dependent for their function on the presence of a nonprotein group. For example, cytochrome c also contains a prosthetic group similar, but not identical, to heme, as do a number of other proteins. These are known generically as heme proteins. There is a family of enzymes that contain a flavin group, the flavoproteins. Another family contains pyridoxal phosphate, a derivative of vitamin Be. There are a number of other examples. 

Flavodoxins are a group of flavoproteins which function as electron carriers at low potential in oxidation-reduction systems. The proteins of this group contain one molecule of FMN as their prosthetic group, but, in contrast to ferredoxins, do not contain metals such as iron. 

Fe S-containing enzymes frequently have other redox-active prosthetic groups, notably, flavins FAD or FMN. Likewise, the redox partner for many Fe S proteins is a flavoprotein this provides a convenient mechanism for turning a one-electron transfer reaction into a two-electron donor/acceptor. Hence, the structures elucidating the interactions between Fe S clusters and other cofactors are of considerable interest. At present there are only two examples for which we have crystallographic structures, yet both provide a basis to propose possible mechanisms for electron transfer to Fe S clusters. 

Table 2. Flavoproteins Containing a Covalently Bound Prosthetic Group ...

The flavoproteins known to contain covalently-found prosthetic groups are listed in Table 2. In addition to the flavoproteins also carcosine oxidase from Corynebacterium contains a covalently-bound FAD Its mode of linkage is not yet known. Furthermore it seems to be the first enzyme reported to contain equivalent amounts of covalently-bound and dissociable FAD. Djmehtlyglycine dehydrogenase prossesses also a covalently linked prosthetic group, which structure is probably identical with that of (2)... 

Many flavoproteins contain, besides the flavocoenzyme, also metal ions as prosthetic groups The study of the interaction between free flavoquinone and d-metal ions is, therefore, of biological interest. In aprotic polar solvents weak complexes are formed Bidentate chelates are formed involving N(5) and the carbonyl... 

The oxygen reactivity of flavohydroquinone bound to apoflavoprotein dehydrogenases can vary considerably from fast (flavodoxins), moderate (xanthine oxidase) to nil (succinate dehydrogenase) Most, but not all, flavoprotein dehydrogenases contain one or more types of metal prosthetic groups, e.g. xanthine oxidase contains also Fe and Mo. Since these metal ions are involved in electron flux, their possible participation in the reaction with O2 cannot be excluded. Much evidence, however, indicates that the flavin is involved in the one-electron reduction of Oj, as shown in Equation (5). 

Capeillere-Blandin, C., Barber, M. J., Bray, R. C. Differences in electron transfer rates among prosthetic groups between two homologous flavocytochrome b2 (L-lactate cytochrome c oxidoreductase) from different yeasts. In Flavins and flavoproteins (Massey, V., Williams, C. H. eds.) pp. 838-843, New York, Amsterdam, Oxford, Elsevier/North Holland 1982... 

The cytochromes P-450 monooxygenase system is actually a collection of isoenzymes, all of which possess an iron protoporphyrin IX as the prosthetic group. The monomer of the enzyme has a molecular weight of 45,000 to 55,000. The enzyme is membrane bound within the endoplasmic reticulum. Cytochromes P-450 are closely associated with another vital component of the system, NADPH cytochrome P-450 reductase. This is a flavoprotein, which has 1 mol of FAD and 1 mol of FMN per mol of apoprotein. The monomeric molecular weight of the enzyme is 78,000. The enzyme transfers two electrons to cytochromes P-450, but one at a time. There only seems to be one reductase, which serves a group of isoenzymes of cytochromes P-450, and consequently, its concentration is 1/10 to 1/30 that of cytochromes P-450. 

NAD(P)H is required in the bioreductions of many xenobiotic compounds. However, NADH or NADPH are not necessarily the entities that directly react with the organic substrate. Rather, the prosthetic groups of other enzymes are themselves reduced by NAD(P)H, and the resulting reduced enzyme components are the actual reactants involved in bond making and breaking of the xenobiotic substance. A prominent set of examples involves the flavin-dependent oxidoreductases. The key reactive portion in these flavoproteins is the three-ring flavin (FAD) which is reduced by NAD(P)H to FADH2 ... 

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