Regulation mechanism dehydrogenase

Yoshiki (29) has studied the biosynthetic pathways of vitamin Bg, including the discovery of the precursor glycolaldehyde, glycolaldehyde dehydrogenase, and isolation of microorganisms deficient in regulation mechanism of Bg biosynthesis. 

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

A similar mechanism has been found for 17(3-hydroxysteroid dehydrogenase (17(3-HSD), the enzyme that regulates the concentrations of estradiol and testosterone in human [5,16,17] (Figure lb). Genetics diseases associated with mutations in this enzyme lead to developmental abnormalities [18]. Enzymes that regulate the concentrations of retinoids [19] and prostaglandins [20] may also have a similar role [6]. 

Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex Is Regulated by Allosteric and Covalent Mechanisms... 

Glucose 6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway, is also regulated by this light-driven reduction mechanism, but in the opposite sense. During the day, when photosynthesis produces plenty of NADPH, this enzyme is not needed for NADPH production. Reduction of a critical disulfide bond by electrons from ferredoxin inactivates the enzyme. 

Three enzymes of the C4 pathway are regulated by light, becoming more active in daylight. Malate dehydrogenase is activated by the thioredoxin-dependent reduction mechanism shown in Figure 20-19 PEP carboxylase is activated by phosphorylation of a Ser residue and pyruvate phosphate dikinase is activated by dephosphorylation. In the latter two cases, the details of how light effects phosphorylation or dephosphorylation are not known. 

Within many tissues the enzymatic activities of the pyruvate and branched chain oxoacid dehydrogenases complexes are controlled in part by a phosphorylation -dephosphorylation mechanism (see Eq. 17-9). Phosphorylation of the decarboxylase subunit by an ATP-dependent kinase produces an inactive phosphoenzyme. A phosphatase reactivates the dehydrogenase to complete the regulatory cycle (see Eq. 17-9 and associated discussion). The regulation is apparently accomplished, in part, by controlling the affinity of the protein for... 

A reversible covalent modification that plants use extensively is the reduction of cystine disulfide bridges to sulf-hydryls. Many of the enzymes of photosynthetic carbohydrate synthesis are activated in this way (table 9.3). Some of the enzymes of carbohydrate breakdown are inactivated by the same mechanism. The reductant is a small protein called thioredoxin, which undergoes a complementary oxidation of cysteine residues to cystine (fig. 9.5). Thioredoxin itself is reduced by electron-transfer reactions driven by sunlight, which serves as a signal to switch carbohydrate metabolism from carbohydrate breakdown to synthesis. In one of the regulated enzymes, phosphoribulokinase, one of the freed cysteines probably forms part of the catalytic active site. In nicotinamide-adenine dinucleotide phosphate (NADP)-malate dehydrogenase and fructose-1,6-bis-... 

Still other enzymes are regulated essentially in on-off fashion. Pyruvate dehydrogenase (PDH), for example, is regulated by phosphorylation-dephosphorylation mechanisms (by protein kinases and protein phosphatases, respectively). The ATP-dependent PDH... 

Understand the physiologic importance and mode of synthesis of glycerol-3-phosphate, 2,3-diphosphoglycerate, and acetyl-CoA understand the mechanism of action and regulation of pyruvate dehydrogenase with all the cofactors involved. 

Fig. 10. Hypothesis for the interaction of the A-kinase (A-K) system activated by ACTH with the C-kinase system (C-K) in the long-term regulation of the enzymes of steroidogenesis throughout the adrenal cortex. The primary determinant of zonation of A-kinase and C-kinase activities, via zonation of cell surface receptors or other mechanisms, is hypothesized to be a gradient (e.g., of steroids) created by the pattern of blood flow in the adrenal cortex. The resultant levels of induction of steroidogenic enzymes are indicated by to show particular elevation and by to show particular lack of induction or suppression of induction. Other enzymes involved in steroidogenesis are shown in parentheses. SCC=cholesterol side-chain cleavage enzyme 3/3=3/3-hydroxysteroid dehydrogenase 17a=17a-hy-droxylase 21 =21-hydroxylase 11/3= 11/3-hydroxylase CMO= corticosterone methyl oxidase activity of 11/3-hydroxylase. Secreted steroids are indicated as B=corticosterone Aldo=aldosterone F=cortisol DHEA(S)= dehydroepiandrosterone (sulfate).

The major enzyme involved in the formation of ammonia in the liver, brain, muscle, and kidney is glutamate dehydrogenase, which catalyzes the reaction in which ammonia is condensed with 2-oxoglutarate to form glutamate (Sec. 15.1). Small amounts of ammonia are produced from important amine metabolites such as epinephrine, norepinephrine, and histamine via amine oxidase reactions. It is also produced in the degradation of purines and pyrimidines (Sec. 15.6) and in the small intestine from the hydrolysis of glutamine. The concentration of ammonia is regulated within narrow limits the upper limit of normal in the blood in humans is 70/tmol L-1. It is toxic to most cells at quite low concentrations hence there are specific chemical mechanisms for its removal. The reasons for ammonia toxicity are still not understood. The activity of the urea cycle in the liver maintains the concentration of ammonia in peripheral blood at 20/ molL. ... 

Whilst these observations point to a potentially important cell-regulatory role for HNE, little is known about factors that control the rate of its production. Clearly a prerequisite is the formation of cellular lipid hydroperoxides, but although levels of those can apparently be modulated by serum factors there is a need to explore mechanisms, possibly enzymatic, whereby HNE levels might be tightly regulated. In this context it is known that HNE can serve as a substrate for glutathione transferase [64], or aldehyde dehydrogenase [66] ... 

Regulation of Pyruvate Dehydrogenase Activity Pyruvate dehydrogenase is the key enzyme that commits pyruvate (and hence the products of carbohydrate metabolism) to complete oxidation (via the tricarboxyUc acid cycle) or lipogenesis. It is subject to regulation by both product inhibition and a phosphorylation/dephosphorylation mechanism. Acetyl CoA and NADH are both inhibitors, competing with coenzyme A and NAD+. 

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