Flavoprotein deficiency

Deficiency of electron transport flavoprotein or of ETF ubiquinone reductase Biotinidase... 

Defects of complex II. These have not been fully characterized in the few reported patients, and the diagnosis has often been based solely on a decrease of succinate-cytochrome c reductase activity (Fig. 42-3). However, partial complex II deficiency was documented in muscle and cultured fibroblasts from two sisters with clinical and neuroradiological evidence of Leigh s syndrome, and molecular genetic analysis showed that both patients were homozygous for a point mutation in the flavoprotein subunit of the complex [17]. This was the first documentation of a molecular defect in the nuclear genome associated with a respiratory chain disorder. 

Table 3.2.5 Disorders detectable by the in vitro probe assay. ETF Electron transfer flavoprotein, MADD multiple acyl-CoA dehydrogenase deficiency...

Riboflavin (vitamin B2) 6,7-dimethyl-9-(D-l-ribityl)isoalloxazine (63), was discovered as a coloring matter in milk in 1879, but its importance was not then realized. Deficiency causes lesions of the eye and of the angle of the mouth. Riboflavin is phosphorylated by adenosine triphosphate (ATP) to give riboflavin 5 -phosphate (flavinadenine mononucleotide, FMN) and then flavinadenine dinucleotide (FAD) (64 R = riboflavin). These function as prosthetic groups in a number of flavoproteins which are dehydrogenation catalysts by virtue of the oxidation-reduction properties of the isoalloxazine system. 

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

The system depends on an electron transport pathway that transfers electrons from NADPH through a flavoprotein (NADPH cytochrome P-450 reductase) to cytochrome P-450 that is the terminal oxidase of the chain (10). The xenobiotic first forms a complex with the oxidized form o cytochrome P-450 which is reduced by an electron passing down the chain from NADPH. The reduced cytochrome P-450/substrate complex then reacts with and activates molecular oxygen to an electrophilic oxene species (an electron deficient species similar to singlet oxygen) that is transferred to the substrate with the concommitant formation of water. Cytochrome P-450 thus acts primarily as an oxene transferase (2). Substrate binding is a relatively nonspecific, passive process that serves to bring the xenobiotic into close association with the active center and provide the opportunity for the oxene transfer to occur. 

In addition to the role of flavoproteins in iron metabolism, it is possible that the anemia associated with riboflavin deficiency is a consequence of the impairment of vitamin Be metabolism in riboflavin deficiency. Pyridoxine oxidase is a flavoprotein and, like glutathione reductase, is very sensitive to riboflavin depletion (McCormick, 1989). Vitamin Be deficiency can result in hypochromic anemia as a result of impaired porphyrin synthesis. Although riboflavin depletion decreases the oxidation of dietary vitamin Be to pyridoxal (Section 9.2), it is not clear to what extent there is secondary vitamin Be deficiency in riboflavin deficiency This is partly because vitamin Be nutritional status is commonly... 

In species for which ascorbate is not a vitamin, riboflavin deficiency can also lead to considerably reduced synthesis and low tissue concentrations of ascorbate, since gulonolactone oxidase, the key enzyme in ascorbate synthesis (Section 13.2), is a flavoprotein. 

Pyridoxine phosphate oxidase is a flavoprotein, and activation of the erythrocyte apoenzyme by riboflavin 5 -phosphate in vitro can be used as an index of riboflavin nutritional status (Section 7.4.3). However, even in riboflavin deficiency, there is sufficient residual activity of pyridoxine phosphate oxidase to permit normal metabolism ofvitamin Be (Lakshmi and Bamji, 1974). Pyridoxine phosphate oxidase is inhibited by its product, pyridoxal phosphate, which binds a specific lysine residue in tbe enzyme. In tbe brain, tbe Ki of pyridoxal phosphate is of the order of 2 /xmol per L - the same as the brain concentration of free and loosely bound pyridoxal phosphate, suggesting that this inhibition may be a physiologically important mechanism in the control of tissue pyridoxal phosphate (Choi et al., 1987). 

Bates CJ (1987) Human riboflavin requirements, and metabolic consequences of deficiency in man and animals. World Review of Nutrition and Dietetics 50,215-65. Ghisla S and Massey V (1989) Mechanisms of flavoprotein-catalyzed reactions. European Journal of Biochemistry ISl, 1-17. 

Glutathione is discussed further in the section on selenium and glutathione in Chapter 10. The enzyme assay is conducted using glutathione reductase extracted from red blood cells with and without added FAD. Chmnic consumption of a diet deficient in riboflavin allows the continued synthesis of a variety of flavoproteins, but results in the accumulation of apoenzyme without its conversion to holoen-zyme. Addition of chemically pure FAD to a biological fluid containing apoenzyme results In the stimulation of enzyme activity because of the formation of the holoenzyme. It is this stimulation of enzyme activity that is used to determine vitamin status in humans. 

CAS 83-88-5. C17H20N4O6. A crystalline pigment, the principal growth-promoting factor of the vitamin B2 complex. It functions as a flavoprotein in tissue respiration. A syndrome resembling pellagra is thought to be due to riboflavin deficiency. 

TheP7007P700 couple has a redox potential of+0.45 V [c/. redox-potential scale in Fig. 2]. The of the Aq/Aq" couple is probably less than -1 V if it is consistent with the in vitro redox-potential value of Chl/Chl of < -1.0 V. The initial charge separation into P700 and Ao would store approximately 1.5 eV out of 1.8 eV of energy of the absorbed 700-nm photon. The redox potential ofthe A,/A," couple is probably -0.8 V. The redox potentials ofthe iron-sulfur centers FeS-X, FeS-B and FeS-A have been experimentally determined to be -0.73, -0.58 and -0.53 V , respectively. The final electron acceptor in photosystem 1 is the [2Fe-2S]-type ferredoxin (Fd) present in the stroma region of the chloroplasts and having a redox potential of -0.4 V. Under iron-deficient growth conditions, a flavoprotein called flavodoxin is synthesized as a replacement acceptor for ferredoxin. 

Amino acid deaminases, IX, 36-38 biotin and, IX, 38-44 Amino acid deficiency, effect on gonads, X, 96-98 Amino acid oxidase (s), action of, IX, 36 biotin and, IX, 54 effect on biotin, X, 337 flavoprotein nature of, IX, 36 in tissues, steroid hormones and, X, 367 D-Amino acid oxidase, effect of adrenalectomy on, X, 320 of steroid hormones on, X, 319, 320, 352-358... 

Riboflavin (V.B lactoflavin 6,7-dimethyl-9-(D-r-ribityl)-isoalloxazine) is a water-soluble yellow flavin derivative, occurring chiefly in a bound form in flavin nucleotides or flavoproteins in yeasts, animal products and legume seeds. Milk contains fiee riboflavin. It is required as a precursor of flavin mononudeotide and flavin-adenine-dinucleotide, which are coenzymes of the flavin enzymes. In rats, experimental riboflavin deficiency causes growth ure and dermatitis around the nostrils and eyes. In hinnans, riboflavin deficiency (ariboflavinosis) is characterized by lip... 

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