Pyruvate kinase activation

Duthie, G.G. and Arthur, J.R, (1987). Blood antioxidant status and plasma pyruvate kinase activity of halothane-reacting pigs. Am. J. Vet. Res. 48, 309-310. 

Most cases are due to decreased expression of pymvate kinase activity, usually to 5-25% of normal levels complete loss of pyruvate kinase activity can cause embryonic death. 

The major end-products of carbohydrate metabolism in this species are lactate and succinate. The relative amount formed of each depends on the presence or absence of oxygen in the incubation medium, the presence or absence of glucose, and the presence or absence of fumarate. For example, anaerobiosis leads to an increase in lactate production, which is accompanied by a fall in the intracellular level of malate. Malate is an inhibitor of pyruvate kinase in M. expansa, so the fall in malate levels results in an increase in pyruvate kinase activity leading to a rise in lactate production. Conversely, under aerobic conditions, malate levels increase, pyruvate kinase activity is inhibited and lactate production is decreased (Fig. 5.5). 

Finally, in the third mammlian grouping (dog, horse, rabbit, seal, swine), the fetal Hb is not expressed. In these species, even without HbF, the 02 affinity of fetal blood is kept higher than that of the adult. This difference is achieved by means of low concentrations of RBC DPG in the fetus and by higher-than-usual concentrations of DPG in the RBCs of adults. In most of these species, this fetal-adult difference in RBC DPG concentration is due to an enhanced catalytic capacity of the terminal part of the glycolytic path (indexed by pyruvate kinase activity, for example), which increases DPG flux towards pyruvate and lactate (see Poyart et ah, 1992). 

Jansen-Duer, P. (1999)Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc. Natl. Acad. Sci. USA 96, 1291-1296. 

Publications on the structure and analytical detection of saponins of Panax ginseng and the effect of ginseng on cholesterol synthesis and pyruvate kinase activity in rats have appeared. New saponins include ginsenosides Rhi (46) and... 

FIGURE 10.51 Pyruvate kinase activity in the presence of a variety of divalent metal ions (O) Mg, (A) Co, ( ) Mn, (A) Ni. (Redrawn with permission from Kwan et al., 1975.)... 

Pyruvate kinase activity Stimulation Casein kinase II Biphasic... 

Insufficient pyruvate kinase activity compromises erythrocyte ATP prodnction, leading to ionic imbalance and misshaped cell membranes. These cells are removed from the circulation by the macrophages of the spleen. 

Liver pyruvate kinase. A plot of pyruvate kinase activity versus PEP concentration is presented. The response of activity to PEP concentration is sigmoidal. Shifts in the curve (one of an infinite number, depending on the concentration of the effectors) in the positive (F-1,6-BP and 6-PG) and negative (alanine) direction are indicated by dashed lines. The physiological range of PEP in liver is shown by the... 

Chronic, heavy, daily alcohol consumption is associated with decreased muscle strength, even when adjusted for other factors such as age, nicotine use, and chronic illness. Heavy doses of alcohol also can cause irreversible damage to muscle, reflected by a marked increase in the activity of creatine kinase in plasma. Muscle biopsies from heavy drinkers also reveal decreased glycogen stores and reduced pyruvate kinase activity. Approximately 50% of chronic heavy drinkers have evidence of type 11 fiber atrophy. These changes correlate with reductions in muscle protein synthesis and serum camosinase activities. Most patients with chronic alcoholism show electromyographical changes, and many show evidence of a skeletal myopathy similar to alcoholic cardiomyopathy. 

Pyruvate kinase Activated by F-1, 6-P inhibited by ATP, aianine inhibited by phosphoryiation (giucagon and epinephrine iead to an increase in cAMP ieveis, which activates protein kinase A)... 

Schematic representation of a lactate dehydrogenase (LDH) - lactate monooxygenase (LMO) sensor for the determination of pyruvate kinase activity. PEP = phosphoenolpyruvate.

Zervoudakis, G. Georgiou, C.D. Angelopoulos, K. Pyruvate kinase activity in crude extracts of leaves of Cynodon dactylon and other C4 plants. Russ. J. Plant Physiol., 48, 171-175 (2001)... 

Modulation of the Mi pyruvate kinase activity also occurs when chick embryo fibroblasts are transformed by Rous sarcoma virus. The pyruvate kinase shows a lower affinity for PEP. The oncoprotein from Rous sarcoma virus pp60 is able to phos-phorylate the Mi pyruvate kinase in vitro (Presek, Remacher Eigenbrodt, 1988). Phosphorylation occurs on a tyrosine residue. Three other glycolytic enzymes have been found to be phosphorylated on tyrosine residues when chick embryo fibroblasts are transformed by Rous sarcoma virus. They are enolase. 

Ochs, R.S. Harris, R.A. (197 ). Studies on the relationship between glycolysis, lipogenesis, gluconeogenesis and pyruvate kinase activity of rat and chicken hepatocytes. Arch. Biochem. Biophys., 190, 193-201. 

Glutamatergic synaptic transmission Pyruvate kinase activity HMG-CoA activity... 

Yanagi S. Sakamoto M. Ninomiya Y Kamiya T. Decrease in L-type pyruvate kinase activity in rat liver by some promoters of hepatocarcinogenesis. J. Natl. Cancer Inst. 1984, 73, 887-894. 

Yanagi, S. Sakamoto, M. Nakano, T. Comparative study on pyruvate kinase activity-reducing action of various promoters of hepatocarcinogenesis. Int. J. Cancer 1986,37,459-464. 

The patient s RBC ADA activity was 43 000 nmol.min . ml RBC " (normal values 495 i 60), There was an about 3-fold increase of red cell pyrimidine 5 -nucleotidase and orotate phosphoribosyl-transferase, whereas other enzymes of purine and pyrimidine metabolism (inosine phosphorylase, adenosine kinase, adenine phosphoribo-syltransferase, hypoxanthine-guanine-phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase) were normal or slightly elevated. There was a 6-fold increase of pyruvate kinase activity relatively to comparably reticulocyte-rich blood, and a 1.5 to 3-fold increase of the other enzymatic activities of glucose and glutathione metabolism. Plasma ADA was much elevated (30.5 pmol.min . ml normal value 5.1 - 2.5), probably reflecting intravascular hemolysis. ADA activity in lymphocytes (2.13 nmol.min 1.10 cells normal 1.93 0.61) and in fibroblasts (26 nmol.min l.mg protein 1 normal range 14-118) was normal, whereas the small increase of activity in platelets (59.5 nmol.min . 10 cells control 26.7) and in the liver (8.4 pmol.min . mg protein" normal ... 

Enzyme Preparation. This enzyme from rabbit muscle is available commercially (Boehringer Manheim Corp.) or may be prepared by the method of Tietz and Ochoa. Further purification may be achieved by the technique of Cottam et al.° Pyruvate kinase activity is conveniently assayed by coupling the reduction of pyruvate, produced from phos-phoenolpyruvate, to lactate, catalyzed by lactate dehydrogenase. The NADH consumed in this reaction is assayed spectrophotometrically. Studies of reversible inhibition are carried out directly in the reaction cuvette, with appropriate controls to eliminate the possibility that inhibition is due to inactivation by DMPA of the lactate dehydrogenase or other assay reagents. 

Feksa LR, Oliveira E, Trombini T, Luchese M, Bisi S, Linden R, et al. Pyruvate kinase activity and 7 delta -aminolevulinic acid dehydratase activity as biomarkers of toxicity in workers exposed to lead. Arch Environ Contam Toxicol 2012 63(3) 453-60. 

Coon and co-workers ttt-ltJia) discovered and crystallized an enzyme Itia) named hydroxylamine kinase that degrades ATP in the presence of bicarbonate and hydroxylamine. It was believed that adenylic acid and pyrophosphate were products of this reaction and it was considered that this enzyme participated in the carboxylation reaction in leucine catabolism by activating COi. Active CO was presumed to be adenyl-COj. Later this enzyme was found not to participate in the carboxylation reactions. More recently Kupiecki and Coon lt4b) established that hydroxylamine kinase is very probably identical with pyruvic kinase and fluoro kinase of Tietz and Ochoa (96). Interesting differences were found in the activation of the different enzyme functions by metal ions. Zn, but not Mg++, promoted hydroxylamine kinase activity, whereas Mg, but not Zn promoted iluorokinase and pyruvic kinase activity. 

Pyruvate kinase, in general, is inhibited by high concentrations of ATP, alanine, acetyl-CoA and long-chain fatty acids. Thus the affinity of the enzyme for its substrate is lowered when energy requirements can be satisfied by other means. Conversely at low [ATP], the affinity of pyruvate kinase for phosphoenolpyruvate (PEP) increases to support the substrate-level phosphorylation of ADP even at low [PEP] because of its inherent instability. The liver isoenzyme is activated by fructose 1,6-bisphosphate so that pyruvate kinase activity is coordinated with variations in... 

R.R. Traxinger and S. Marshall, J. Biol Chem., 1992, 267, 9718-9723, Insulin Regulation of Pyruvate Kinase Activity in Isolated Adipoeytes Crucial Role of Glucose and the Hexosamine Biosynthesis Pathway in the Expression of Insulin Action. 

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