Coenzyme effects

Coenzymes effecting transfer of groups. Examples of this class are adenosine triphosphate (ATP), biotin, coenzyme A and pyridoxal phosphate. 

Coenzymes effecting isomerization. Pyridoxal phosphate also falls into this class,... 

Ascorbic acid deficiency also reduces the activity of several dehydrogenases involved in the Krebs cycle. The mechanism by which the vitamin leads to such alteration is not clear, but the effect is reversed by insulin administration. Thus, miscellaneous observations on the effect of ascorbic acid on carbohydrate metabolism have been made, but they are difficult to interpret because no specific coenzyme effect of ascorbic acid has been demonstrated. Again, ascorbic acid is assumed to be directly involved in an electron transport chain that involves cytochrome and NAD. The vitamin may also affect the electron transport chain indirectly because a decrease in NADH concentration has been observed in vitamin C deficiency. But this decrease may also result from an interference with the insulin production because it is... 

The enzyme which catalyzes the formation of tryptophan from indole and serine has been named tryptophan desmolase. A cell-free preparation has been obtained from Neurospora mycelium which catalyzes this reaction. Pyridoxal phosphate has been found to be a necessary cofactor. The enzyme has been partially purified by Yanofsky. He found the optimum activity to be at pH 7.8, and confirmed the necessity of pyridoxal phosphate as a coenzyme. Effective inhibitors are Co++, Zn++, CN, hydroxylamine, and tryptophan. 

The first two of these are mediated by 5 -deoxyadenosylcobalamin, whereas methyl transfers are effected by methylcobalamin. The mechanism of ribonucleotide reductase is discussed in Chapter 27. Methyl group transfers that employ tetrahydrofolate as a coenzyme are described later in this chapter. 

Fontes, R., Dukhovich, A., Sillero, A., and Gunther Sillero, M. A. (1997). Synthesis of dehydroluciferin by firefly luciferase, effect of dehydrolu-ciferin, coenzyme A and nucleoside triphosphates on the luminescence reaction. Biochem. Biophys. Res. Commun. 237 445—450. 

It was confirmed, by separating the enzymes in the powder, that many S- and R-directing enzymes do indeed exist in the dried cells. The addition of a coenzyme and cyclopentanol stimulates only an S enzyme because the specific S enzyme can oxidize cyclopentanol (concomitantly reducing NAD(P) ), while other S or R enzymes cannot use cyclopentanol as effectively [14cj. This presents a very interesting case, where the experimental conditions of reduction with a cell having both S-and R-directing enzymes was modified and resulted in excellent S enantioselectivity. 

Figure 8.27 Reduction of aldehyde in SCCO2 by an isolated enzyme, horse liver alcohol dehydrogenase (HLADH) [20c] (a) Reaction scheme (b) fluorinated coenzyme soluble in CO2 and (c) effect of coenzyme on the reaction.

Figure 3. Addition, of the GOT coenzymes pyridoxal and pyridoxamine phosphates in concentrations up to 200 /tg/ml lias no effect on human serum GOT but activates bu 45% the pig heart GOT activity of VersatoUE, a commercial reference serum...

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

To clarify the characteristics of AMDase, the effects of some additives were examined using phenylmalonic acid as the representative substrate. The addihon of ATP and coenzyme A did not enhance the rate of the reaction, different from the case of malonyl-CoA decarboxylase and others in those, ATP and substrate acid form a mixed anhydride, which in turn reacts with coenzyme A to form a thiol ester of the substrate. In the present case, as both ATP and CoA-SH had no effect, the mechanism of the reaction will be totally different from the ordinary one described above. It is well estabhshed that avidin is a potent inhibitor of the formation of the biotin-enzyme complex. In the case of AMDase, addition of avidin has no influence on the enzyme activity, indicating that AMDase is not a biotin enzyme. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

The very high resolution for the ESR spectrum of cob(II)alamin in the enzyme system is undoubtedly due to the fact that all the coenzyme molecules are bound in an identical environment at the enzyme active site. This results in a homogeneous cobalt-benzimidazole geometry, because both identical binding sites, solvent, and solute molecules can no longer approach the Bia-molecule closely. In addition, the enzyme bound cob(II)alamin molecules are more isolated from one another and thus relaxation due to spin-spin interactions is less effective in broadening spectral lines. 

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