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Pyruvate kinase inhibition

Pyruvate kinase inhibition. The seed, administered to male rats at a dose of 5% of diet, was active in plasma vs low-a-toco-pherol diet. Results were significant at p < 0.05 level ". ... [Pg.497]

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... [Pg.630]

Acetyl-CoA is a potent allosteric effector of glycolysis and gluconeogenesis. It allosterically inhibits pyruvate kinase (as noted in Chapter 19) and activates pyruvate carboxylase. Because it also allosterically inhibits pyruvate dehydrogenase (the enzymatic link between glycolysis and the TCA cycle), the cellular fate of pyruvate is strongly dependent on acetyl-CoA levels. A rise in... [Pg.750]

Let us consider Figure 5.3 again. Both pyruvate kinase and dtrate synthase (enzymes III and V) are inhibited by elevated ATP concentrations. During citric acid production ATP concentrations are likely to arise (ATP produced in glycolysis) and either of these enzymes could, if inhibited, slow down the process. In fact all of the evidence suggests that both enzymes are modified or controlled in some way such that they are insensitive to other cellular metabolites during citric add production. [Pg.128]

Adenosine 5 -hypophosphate (23), an analogue of ADP, can undergo phosphorylation by PEP and pyruvate kinase to yield (24). Adenylate kinase which catalyses the scission of the bond between the a and j8 phosphorus atoms in ADP is, not surprisingly, inhibited competitively by (23). [Pg.129]

In biological systems, therefore, the behavior of Li+ is predicted to be similar to that of Na+ and K+ in some cases, and to that of Mg2+ and Ca2+ in others [12]. Indeed, research has demonstrated numerous systems in which one or more of these cations is normally intrinsically involved, including ion transport pathways and enzyme activities, in which Li+ has mimicked the actions of these cations, sometimes producing inhibitory or stimulatory effects. For example, Li+ can replace Na+ in the ATP-dependent system which controls the transport of Na+ through the endoplasmic reticulum Li+ inhibits the activity of some Mg2+-dependent enzymes in vitro, such as pyruvate kinase and inositol monophosphate phosphatase Li+ affects the activity of some Ca2+-dependent enzymes— it increases the levels of activated Ca2+-ATPase in human erythrocyte membranes ex vivo and inhibits tryptophan hydroxylase. [Pg.5]

In addition to the aforementioned allenic steroids, prostaglandins, amino acids and nucleoside analogs, a number of other functionalized allenes have been employed (albeit with limited success) in enzyme inhibition (Scheme 18.56) [154-159]. Thus, the 7-vinylidenecephalosporin 164 and related allenes did not show the expected activity as inhibitors of human leukocyte elastase, but a weak inhibition of porcine pancreas elastase [156], Similarly disappointing were the immunosuppressive activity of the allenic mycophenolic acid derivative 165 [157] and the inhibition of 12-lipoxygenase by the carboxylic acid 166 [158]. In contrast, the carboxyallenyl phosphate 167 turned out to be a potent inhibitor of phosphoenolpyruvate carboxylase and pyruvate kinase [159]. Hydrolysis of this allenic phosphate probably leads to 2-oxobut-3-enoate, which then undergoes an irreversible Michael addition with suitable nucleophilic side chains of the enzyme. [Pg.1031]

Treatment of 9-(/ -D-ribofuranosyluronic acid)adenine with diphenylphosphoro-chloridate and orthophosphate or tripolyphosphate yields (62) and (63), which, although unstable, inhibit rabbit AMP aminohydrolase and pyruvate kinase, respectively, with behaviour characteristic of active-site-specific reagents.98 Adenylate kinases from several sources are inactivated by iV6-[2- and 4-fluorobenzoyl]-adenosine-5 -triphosphates, with kinetics characteristic of active-site labelling, although these compounds were without effect on yeast hexokinase and rabbit pyruvate kinase.99... [Pg.166]

Specific ion requirements for many enzymes are very well documented, and it could be expected that such enzymes showed special relations between AV and salt concentration. This also seemed to be the case in the experiments of Low and Somero (1975b). From 2.2 M ammonium sulfate, pyruvate kinase with specific cation (K+, NH4+) binding sites gave much stronger titration effects for dialyzed samples than for freshly diluted samples. This indicated that retention of ions at the binding sites partly inhibited the strong AVf dependence on salt concentration. [Pg.140]

Sodium fluoride (104) (1-10 mM) inhibits two enzymes of glycolysis the enolase (phosphopyruvate hydratase) and pyruvate kinase. Therefore, aerobic glucose utilization and lactate formation are blocked. [Pg.365]

Facilitated diffusion within organisms takes place when carriers or proteins residing within membranes—ion channels, for instance—organize the movement of ions from one location to another. This diffusion type is a kinetic, not thermodynamic, effect in which a for the transfer is lowered and the rate of diffusion is accelerated. Facilitated diffusion channels organize ion movements in both directions, and the process can be inhibited both competitively and noncompetitively. It is known that most cells maintain open channels for K+ most of the time and closed channels for other ions. Potassium-ion-dependent enzymes include NaVK+ ATPases (to be discussed in Section 5.4.1), pyruvate kinases, and dioldehydratases (not to be discussed further). [Pg.197]

Pyruvate kinase, the activity of which is inhibited by ATP and phosphocreatine but is activated by ADP, which is its substrate (Figure 6.16(a)). [Pg.108]

K+. Pyruvate kinase is inhibited by 3-5 mM ATP, as well as by acetyl-S-CoA and long-chain fatty acids. Rabbit muscle pyruvate kinase is typically used in ATP regeneration. [Pg.518]

Figure 6-1. The steps of glycolysis. Feedback inhibition of glucose phosphorylation by hexokinase, inhibition of pyruvate kinase, and the main regulatory, rate-limiting step catalyzed by phosphofructoki-nase (PFK-I) are indicated, pyruvate formation and substrate-level phosphorylation are the main outcomes of these reactions. Regeneration of NAD occurs by reduction of pyruvate to lactate during anaerobic glycolysis. Figure 6-1. The steps of glycolysis. Feedback inhibition of glucose phosphorylation by hexokinase, inhibition of pyruvate kinase, and the main regulatory, rate-limiting step catalyzed by phosphofructoki-nase (PFK-I) are indicated, pyruvate formation and substrate-level phosphorylation are the main outcomes of these reactions. Regeneration of NAD occurs by reduction of pyruvate to lactate during anaerobic glycolysis.
Pyruvate kinase is inhibited by compounds that are elevated when the cell has high energy reserves or molecules with potential for energy generation. [Pg.73]

Exploration of Bulk Tolerance at ATP Sites. Non-covalent type inhibitors have also been used to study bulk tolerance around the ATP binding sites. In this vein Hampton and co-workers have both synthesized and tested as inhibitors a large number of adenine nucleotide analogs (Figure 2f) to probe the bulk tolerance at a number of positions on the parent compound (28-31) These compounds have been used to study systematically the isoenzyme selectivity of adenylate kinases, hexokinases, thymidine kinases and pyruvate kinases with respect to bulk tolerance at many sites on the ATP molecule. Some of the most isoenzyme specific results were obtained with pyruvate kinase isoenzymes K,L and M using ADP derivatives. Here 3 -0Me-ADP was found to inhibit pyruvate kinase preferentially with a ratio of inhibitory potency of 7.6 6.0 1.0 for the K,M and L isoenzymes, respectively. Another compound, 8-NHEt-ADP, was selective for the M isoenzyme, giving a ratio of 7.1 1.2 1.0 for the M, K and L forms, respectively. [Pg.194]

Pyruvate kinase is allosterically inhibited by ATP, and the liver isozyme is inhibited by cAMP-dependent phosphorylation. [Pg.583]

Potassium is required for enzyme activity in a few special cases, the most widely studied example of which is the enzyme pyruvate kinase. In plants it is required for protein and starch synthesis. Potassium is also involved in water and nutrient transport within and into the plant, and has a role in photosynthesis. Although sodium and potassium are similar in their inoiganic chemical behavior, these ions are different in their physiological activities. In fact, their functions are often mutually antagonistic. For example, K+ increases both the respiration rate in muscle tissue and the rate of protein synthesis, whereas Na+ inhibits both processes (42). [Pg.536]


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See also in sourсe #XX -- [ Pg.73 ]




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