Oxidative phosphorylation vitamin

The term vitamin K2 was applied to 2-methyl-3-difarnesyl-l,4-naphthoquinone, m.p. 54 C, isolated from putrefied fish meal. It now includes a group of related natural compounds ( menaquinones ), differing in the number of isoprene units in the side chain and in their degree of unsaturation. These quinones also appear to be involved in the electron transport chain and oxidative phosphorylation. 

The Mechanism of Oxidative Phosphorylation 1066 Box 18-D Vitamin C Ascorbic Acid... 

It has been reported that vitamin Kj and several of the vitamin K2 homologues are capable of restoring electron transport in solvent-extracted or irradiated bacterial and mitochondrial preparations. Other reports suggest that vitamin K is concerned with the phosphorylation reactions accompanying oxidative phosphorylation The capacity of these compounds to exist m several forms, e.g., quinone, quinol. chromanol, etc., appears to strengthen the proposal that links them to oxidative phosphorylation. Information has suggested that vitamin K acts to induce prothrombin synthesis. Since prothrombin has been shown to be synthesized only by liver parenchymal cells m the dog, it would appear that the proposed role for vitamin K is not specific for only prothrombin synthesis, but applicable to other proteins. 

Now that it is established that cestodes possess all the components of a electron transport system, is the latter functional Weinbach von Brand (952) failed to demonstrate either respiratory control or oxidative phosphorylation in T. taeniaeformis, although they regarded this as a technical rather than a physiological problem. However, there is good evidence that isolated mitochondria from M. expansa (124-127) and H. diminuta (663, 978) are capable of oxidative phosphorylation and respiratory control. The demonstration that a preparation of H. diminuta mitochondria will oxidise a range of substrates, exhibiting respiratory control, is shown in Table 5.14. Similarly, mitochondria from Diphyllo-bothrium latum can oxidise NADH (728) and succinate (729). It is likely that the classical mammalian-type part of the cytochrome chain in cestodes is capable of oxidative phosphorylation, but there is no evidence for ATP synthesis occurring on the alternative branch from the quinone or vitamin K/cytochrome b complex to cytochrome o. 

The involvement of oxidative stress in AD has opened a new door for potential therapeutic targets. In this regard, several antioxidants are currently in clinical trials such as Idebenone, a-Lipoic acid, acetyl-L-carnitine (ALC), vitamin E, vitamin C, flavonoids, P-carotene, gingko biloba, and metal-chelating agents. Idebenone is a metabolic antioxidant and is normally synthesized as part of the mitochondrial oxidative phosphorylation system. Improvements in clinical status after treatment with idebenone have been shown in a dose-dependent manner compared to placebo and tacrine (Thai et al., 2003). 

Vitamins and K2 exist in nature and are essential to the animal for their effect on the blood-clotting mechanism. While 2-methylnaphthoquinone itself and its related derivatives having isoprenoid side chains in position 3 also promote blood coagulation in varying degrees, coenzyme Q10 shows no activity in the blood-coagulating mechanism. Coenzyme Q10, also called ubiquinone because of its ubiquitous occurrence in animal tissues, is important in its own right, since it plays an essential role in oxidative phosphorylation. As in the case of the vitamin K series, the size of the isoprenoid side chain does not appear to be critical with respect to the oxidative phosphorylation activity of the coenzyme Q series. 

Quinones are firmly established in photosynthesis models. But how about vitamins E and K How do quinones work in animals First of all they transport electrons in a similar way as in photosynthesis (Metzler, 1977 Voet, 1990). Second, tocopherol is known to act as an antioxidant or radical quencher. The radical chain starting with the decomposition of unsaturated lipid peroxides, for example, is inhibited by tocopherol, which produces long-lived semiquinone radicals (Scheme 7.2.10). Vitamin E prevents, for example, sterility in rats fed rancid lipids. Vitamin E in connection with carotenes is also used as a stabilizer for diet margarines containing large amounts of essential fatty acids. Another possible activity of tocopherol is participation in oxidative phosphorylation a hydroquinone is mono-esterified with phosphoric acid to form a quinol phosphate and then oxidized to the quinone. The cationic quinone-phosphate adduct then reacts with anionic phosphate to form pyrophosphate (Scheme 7.2.10), (Wang, 1969 Breslow, 1980 Isler and Brubacher, 1982). 

Once the nature of the unsaturation in the C17 chain was established, we considered if this structural feature had an active role in function or could we say nature has just been too lazy to reduce these double bonds to give a saturated polyisoprenoid group. Possibly related in function are the similarly unsaturated, though frequently much longer, isoprenoid chains of ubiquinones, vitamin K s, and related compounds, substances also implicated in electron-transfer and/or oxidative phosphorylation processes. Thus, the C17 group in heme A may be directly related to either electron transfer or coupling of phosphorylation in the oxidase. 

OH-D3-24-hydroxylase has also been demonstrated to occur in the kidney but not exclusively so This enzyme also hydroxyUtes 1,25-(0H)2D3 to form 1.24R,25-(OH)3D3 A 244iydroxylase has also been located in intestine which apparently is more specific for l,25-(OH)2D3 Another 24-hydroxylase has been reported in cartilage tissue The chick kidney reaction occurs in the mitochondria and in general is similar to the 25-OH-D3-la-hydroxy-lase In intact mitochondria it is supported by Krebs cycle substrates, utilizes molecular oxygen and is blocked by inhibitors of oxidative phosphorylation. In calcium swollen mitochondria, NADPH will support the reaction and under these circumstances the reaction is independent of the electron transport stem and oxidation phosphorylation. However, this reaction is not carbon monoxide sensitive and does not appear to be dependent upon cytochrome P-450. It is, however, a mbced-function monooxygenase as demonstrated by 02 experiments It is induced by 1,25-(OH)2D3 and is absent in vitamin D-deficient tissue Its substrate specificity is similar to that of the 25-OH-D3-la-hydroxylase. It has not been further studied nor has it been successfully solubilized at the present time. 

Novobiocin does not belong to any particular chemically defined group of antibiotics although there are a number of groupings in e molecule which may be related to specific effects. The antibiotic is a coumarin derivative (I) (see p. 40) and has been shown to inhibit oxidative phosphorylation in Mycobacterium phlei [82]. A vitamin K compound is necessary for electron transport in this organism, and both novobiocin-induced inhibition of electron transport and inhibition of growth are reversed by vitamin K. 

Vitamins of the K series ("Coagulation" vitamins) are chemically classified as prenyl-1,4-naphthoquinones. They are ingested with food originating from all green plants, are involved in oxidative phosphorylation during respiration processes and... 

Vitamin B2 (riboflavin) occurs in green vegetables, yeast, liver, and milk, it is a constituent of the coenzymes FAD and FMN, which have an important role in the metabolism of all major nutrients as well as in the oxidative phosphorylation reactions of the electron transport chain. Deficiency of B2 causes inflammation of the tongue and lips, mouth sores, and conjimctivitis. 

On the basis of these observations, Martins has proposed a scheme in which vitamin K influences electron transfer between NAD, flavoprotein, and cytochrome b. This view was further supported when a reductase was discovered that catalyzes the oxidation of NADH in the presence of vitamin K. It has not yet been established whether the reduced vitamin K can be oxidized in turn by the respiratory chain. The mechanism by which vitamin K affects oxidative phosphorylation is not clear. 

Vitamin E is abundant in the heart it is thought to be concentrated entirely in heart mitochondria. The concentration of vitamin E in the heart is in keeping with the concentration of the other components involved in the electron transport chain. Vitamin E-defi-cient animals have increased respiration rates. These findings have been thought ot indicate that vitamin E plays a role in the control of oxidative phosphorylation. It was also observed that isooctane extraction of various enzyme preparations leads to inactivation of NADH oxidase, succinoxidase, and cytochrome oxidase systems. The inactivation can be restored to normal by adding vitamin E to the system however, the reactivation is completely nonspecific, and a variety of lipids may have the same effect [120, 121]. 

Thiamine, biotin, pantothenic acid, riboflavin and vitamin B12 are involved in propionic acid fermentation. Biotin forms the prosthetic group of methyl-malonyl-CoA transcarboxylase pantothenate is a constituent of CoA thiamine is not the coenzyme (co-carboxylase) of the enzyme carboxylase like in other organisms, for acetaldehyde has not been detected in propionibacteria (although traces were recently found), but it may function as a component of dehydrogenases in oxidative phosphorylation of a-keto acids. Riboflavin is a constituent of FAD and FMN. Propionibacteria can synthesize vitamins B2 and B in considerable amounts (see below), but the other three vitamins must be supplied. Some strains can grow in synthetic media without thiamine (Silverman and Workman, 1939 Delwiche, 1949), in some other strains thiamine can be replaced by / -aminobenzoic acid. 

Bruchatcheva NL, Bonarceva GA and Vorobjeva LI (1975) Oxidative phosphorylation in propionic acid bacteria. Mikrobiologiya 44 11-15 Bukin VN, Bykhovsky VY and Panzchava ES (1971) Vitamin B and its apphcation in husbandry. Nauka, Moscow... 

In human and other mammalian populations, heme is the functional cofactor for critical diverse metabolic processes in the body such as oxygen transport by hemoglobin and myoglobin, the operation of various cytochromes in oxidative processes ranging from oxidative phosphorylation and detoxification of organic xenobiotics to enzymatically mediated formation of the hormonal form of vitamin D in kidney. 

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