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PubMed2000

Pyruvate potentiates inotropic effects of isoproterenol and Ca(2+) in rabbit cardiac muscle preparations.

Catecholamines and elevated extracellular Ca(2+) concentration ([Ca(2+)](o)) augment contractile force by increased Ca(2+) influx and subsequent increased sarcoplasmic reticulum (SR) Ca(2+) release. We tested the hypothesis that pyruvate potentiates Ca(2+) release and inotropic response to isoproterenol and elevated [Ca(2+)](o), since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37 degrees C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca(2+)](o) of 1.25 mM, pyruvate (10 mM) alone increased developed force (F(dev)) from 1.89 +/- 0.42 to 3.62 +/- 0.62 (SE) mN/mm(2) (n = 8, P < 0.05) and isoproterenol (10(-6) M) alone increased F(dev) from 2.06 +/- 0. 55 to 25.11 +/- 2.1 mN/mm(2) (P < 0.05), whereas the combination of isoproterenol and pyruvate increased F(dev) overproportionally from 1.89 +/- 0.42 to 33.31 +/- 3.18 mN/mm(2) (P < 0.05). In a separate series of experiments, we assessed SR Ca(2+) content by means of rapid cooling contractures and observed that, despite no further increase in F(dev) by increasing [Ca(2+)](o) from 8 to 16 mM, 10 mM pyruvate could still increase F(dev) from 26.4 +/- 6.8 to 29.7 +/- 7. 1 mN/mm(2) (P < 0.05, n = 9) as well as the Ca(2+) load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca(2+), because in the presence of pyruvate, Ca(2+) and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

Animals↗
PubMed1995

Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart. Modulation with pyruvate and lactate.

The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+i). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements of Na+i and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+i and Ca2+i were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+i increases and substantial K+i depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+i occurred before substantial Na+i accumulation or K+i depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+i and K+i, whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+i accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+i was not supported.

Animals↗
PubMed1994

Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy.

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin.

Brain↗
PubMed2001

Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia.

Human erythrocyte pyruvate kinase plays an important role in erythrocyte metabolism. Mutation on the gene results in pyruvate kinase deficiency and is an important cause of hereditary nonspherocytic hemolytic anemia. Because of difficulties in isolating the mutant enzymes from patients, these mutations have not been fully studied. In this study, a complementary DNA (cDNA) encoding the human erythrocyte pyruvate kinase was generated. The cDNA was cloned into several expression vectors, and the protein was expressed and purified. The tetrameric protein exhibited properties characteristic of authentic human erythrocyte pyruvate kinase, including response to substrate, phosphoenolpyruvate, activation by fructose 1,6-bisphosphate, and inhibition by adenosine triphosphate (ATP). The N-terminal segment of the protein was highly susceptible to proteolysis, but only 2 of the 4 subunits were cleaved and lacked 47 N-terminal amino acid residues. A mutant protein, R510Q, which is the most frequently occurring mutation among Northern European population, was also generated and purified. The mutant protein retained its binding capacity to and could be activated by fructose 1,6-bisphosphate and showed similar kinetics toward phosphoenolpyruvate and adenosine diphosphate as for the wild-type enzyme. Conversely, the mutant protein has a dramatically decreased stability toward heat and is more susceptible to ATP inhibition. The enzyme instability decreases the enzyme level in the cell, accounting for the clinically observed "pyruvate kinase deficiency" of patients who are homozygous for this mutation. This study provides the first detailed functional characterization of human erythrocyte pyruvate kinase. These findings will allow the establishment of a fine correlation between molecular abnormalities and the clinical expression of the disease.

Adenosine Triphosphate↗
PubMed2003

Cerebrospinal fluid lactate and pyruvate concentrations and their ratio in children: age-related reference intervals.

BACKGROUND: Lactate (L) and pyruvate (P) concentrations in cerebrospinal fluid (CSF) and the L/P ratio have diagnostic value in numerous primary and acquired disorders affecting the central nervous system, but age-related reference values are not available for children. METHODS: We analyzed CSF and blood lactate and pyruvate concentrations and their ratio in a 4-year retrospective survey of a children's hospital laboratory database. Reference intervals (10th-90th percentiles) were established from data on 197 hospitalized children. A recent regression modeling method was used to normalize and smooth values against age. The model equation of best fit was calculated for each variable. RESULTS: Slight age-related variations were shown by the model, with an increase in lactate, a decrease in pyruvate, and a resulting increase in the L/P ratio with increasing age. However, the SD did not vary with age. We defined the upper limit of the reference intervals as the 90th percentiles, which from birth to 186 months of age varied continuously from 1.78 to 1.88 mmol/L (6%), 148 to 139 micro mol/L (6%), and 16.9 to 19.2 (14%) for lactate, pyruvate, and the L/P ratio, respectively. At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively. CONCLUSIONS: In children, CSF lactate and pyruvate concentrations and their ratio appear to vary slightly with age. Average 90th percentile values of 1.8 mmol/L, 147 micro mol/L, and 17, respectively, could be used in infants up to 24 months of age. In older children, age-adjusted reference intervals should be used, especially when values are close to the 90th percentile.

Adolescent↗
PubMed1981

Calcitonin increases pyruvate carboxylase activity in hepatic mitochondria of rats.

The effect of calcitonin (CT) on calcium content and enzyme activity in the hepatic mitochondria of intact rats was investigated. A single subcutaneous administration of CT (80 MRC mU/100 g BW) produced a significant increase in the content of calcium, the activity of pyruvate carboxylase, succinate dehydrogenase and ATPase 15 min after the hormone treatment. The significant increases in calcium content and pyruvate carboxylase activity were also observed 30 min after CT administration, while succinate dehydrogenase and ATPase activity began to decrease. A physiological dose of CT (20 MRC mU/100 g BW) caused a marked increase in calcium content and pyruvate carboxylase activity but not succinate dehydrogenase of ATPase-activity. The removal of calcium by 10 mM EGTA washing of the mitochondria produced a remarkable reduction in pyruvate carboxylase activity increased by CT administration. The addition of calcium ion of 2.5 x 10(-2) - 2.5 x 10(1) nmoles Ca2+ per mg mitochondrial protein produced a marked increase in pyruvate carboxylase activity. The present results suggest that calcium taken up by the hepatic mitochondria after CT administration activates pyruvate carboxylase.

Adenosine Triphosphatases↗
PubMed2005

Lysophosphatidic acid affinity chromatography reveals pyruvate kinase as a specific LPA-binding protein.

Lysophosphatidic acid is a pleiotropic lipid signaling molecule that evokes a broad array of cellular responses including proliferation, tumor cell invasion, neurite retraction, cytoskeletal rearrangements and smooth muscle contraction. Generally, lysophosphatidic acid triggers physiological responses through interaction with specific plasma membrane receptors called LPA 1-4. There is, however, increasing evidence in support of intracellular proteins that interact with LPA. We employed Affigel-immobilized LPA to isolate cytoplasmic proteins that interact with this lysophospholipid. Among the proteins retained by this affinity matrix, pyruvate kinase, clathrin heavy chain and heat shock protein 70 (Hsp70) were identified by mass spectrometry. Isothermal titration calorimetry showed that pyruvate kinase contains one binding site for LPA (Ka approx. 10(6) M(-1)). Furthermore, LPA dissociates enzymatically active pyruvate-kinase tetramers into less active dimers, and is maximally active at concentrations close to its critical micelle concentration. These effects were not mimicked by other lysophospholipids. Co-immunoprecipitation experiments showed that pyruvate kinase interacts with clathrin, and confocal imaging revealed co-localization between clathrin and pyruvate kinase in the perinuclear region of cells. Our data suggest that pyruvate kinase partly exists in complex with clathrin in subcellular membranous areas, and that locally increased LPA levels can trigger inactivation of the metabolic enzyme.

Animals↗
PubMed1983

Decreased flux through pyruvate dehydrogenase by thiol oxidation during t-butyl hydroperoxide metabolism in perfused rat liver.

Addition of t-butyl hydroperoxide to isolated perfused rat liver leads to a decreased flux through pyruvate dehydrogenase, shown by a decreased 14CO2 release from [1-14C]pyruvate. The effect is observed at rates of infusion of t-butyl hydroperoxide exceeding 0.7 mumol per min per g liver in normal livers and at significantly lower rates in glutathione-depleted livers. The effect is absent in livers from Se-deficient rats in which the hepatic Se-dependent glutathione peroxidase activity is very low, indicating that reduction of t-butyl hydroperoxide by glutathione peroxidase is a necessary prerequisite for the inhibition. With isolated mitochondria, decreased 14CO2 release from [1-14C]pyruvate during t-butyl hydroperoxide metabolism correlates with decreased GSH and increased GSSG contents, respectively. The addition of various disulfide compounds, including GSSG, inhibits activity of the enzyme in mitochondrial extracts. In both mitochondria and perfused liver, t-butyl hydroperoxide-mediated decrease of pyruvate dehydrogenase flux is relieved by thiol reductants. The active (dephospho)form of pyruvate dehydrogenase as measured in freeze-stopped liver samples is actually increased from 46% to 72% during t-butyl hydroperoxide metabolism. The tissue levels of ATP and ADP and perfusate beta-hydroxybutyrate/acetoacetate ratio are not markedly perturbed by addition of the hydroperoxide (10 min). It is concluded that the decreased flux through pyruvate dehydrogenase during t-butyl hydroperoxide metabolism results from oxidation of critical thiol group(s) of the enzyme complex consequential to a decrease in mitochondrial GSH/GSSG.

Animals↗
PubMed1983

Red blood cell age, pyruvate kinase activity, and insulin receptors. Evidence that monocytes and RBCs may behave differently.

Data emerging from insulin receptor studies performed on red blood cells (RBCs) and monocytes from the same subject are not always in agreement; dichotomy might occur since variations in mean RBC age are not taken into account or because insulin receptors on the two cell types behave differently. In the present investigation RBCs from normal male subjects were separated into five populations of different mean age by means of centrifugation of RBCs on a discontinuous gradient of buffered Percoll for 10 min at 1000 X g. Insulin binding varied significantly depending upon the RBC population tested and was closely correlated to the activity of pyruvate kinase (r2 = 0.86), a well-known marker of RBC age. These data suggested that pyruvate kinase assay might be helpful in studies of RBCs. To confirm this hypothesis, RBCs from 10 normal male subjects and 13 male patients with hemolytic anemia were studied; insulin binding was correlated to pyruvate kinase activity. By adjusting insulin binding to 2 X 10(9) RBCs/ml the range of data was abnormally high, but it became acceptable after adjusting insulin binding to pyruvate kinase activity (0.75 U/2 X 10(9) RBCs). The overall data indicated that insulin binding was highly correlated to pyruvate kinase activity (r2 = 0.82) but only slightly to reticulocyte number (r2 = 0.56) since not only reticulocytes but also erythrocytes lose receptors during maturation. Pyruvate kinase activity was measured in RBCs from normal men and from normally menstruating women at the seventh and twenty-fourth days of the cycle; results demonstrated that adjustment of data, according to mean RBC age, broadens dichotomy of monocyte and RBC data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.

Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis. Activation of the complex promotes disposal of glucose, whereas inactivation conserves substrates for hepatic glucose production. Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex. The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle. Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria. Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes. These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions. It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle. Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.

Animals↗
PubMed2005

Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment.

Hypoglycemia-induced brain injury is a significant obstacle to optimal blood glucose control in diabetic patients. Severe hypoglycemia triggers a cascade of events in vulnerable neurons that may culminate in cell death even after glucose normalization. A key event in this cascade is the activation of poly(ADP-ribose) polymerase-1 (PARP-1). Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. Here we tested whether pyruvate could improve the outcome in rats subjected to insulin-induced hypoglycemia by terminating hypoglycemia with either glucose alone or glucose plus pyruvate. In the four brain regions studied--CA1, subiculum, dentate gyrus of the hippocampus, and piriform cortex--the addition of pyruvate reduced neuron death by 70-90%. Improved neuron survival was also observed when pyruvate delivery was delayed for up to 3 h. The improved neuron survival was accompanied by a sustained improvement in cognitive function as assessed by the Morris water maze. These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.

Animals↗
PubMedDate not supplied

Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK).

OBJECTIVE: The evaluate a potential tumor marker for RCC. Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolyticflux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M2. To establish the expansion of phosphometabolite pools pyruvate kinase switches between a tetrameric form with high phosphoenol-pyruvate (PEP) affinity and a dimeric form with a lower PEP affinity. The dimeric form is predominant in all tumors that have been investigated and has been termed TuM2Pk. MATERIALS AND METHODS: We studied: a) the expression of TuM2Pk in RCC by immunohistochemistry using a monoclonal antibody recognizing only the mono- or dimeric form of pyruvate kinase, b) the stability of TuM2Pk in serum by measuring TuM2Pk in 3 patients at different times after taking blood with a two-site immunometric assay, c) the a circadiane rhythm of TuM2Pk in blood by measuring levels every 4 hours in 5 patients, d) TuM2Pk- expression in serum (see 2.) in 5 patients by taking blood from tumor-side vena renalis compared to peripherally blood, e) TuM2Pk (see point 2.) in 40 RCC-patients comparing the results with 39 healthy persons and clinical data of RCC, f) the influence of wound healing to TuM2Pk by measuring serum-levels during a period of more than 12 weeks in 6 patients, g) the individual follow up of 4 patients with RCC stage Robson III for more than 2 years. Comparing TuM2Pk-levels to findings of staging by computed tomography. RESULTS: The isoenzyme TuM2Pk could be demonstrated in RCC and their metastases by immunohistochemistry with a monoclonal antibody specific for pyruvate kinase type M2. In normal kidney cells pyruvate kinase type M2 is not detectable. The stability of TuM2Pk was studied in the serum within 30 minutes. No circadian rhythm was found. Most serum TuM2Pk comes from tumor. Serum evaluation in 39 healthy persons was used to determine normal values, with an upper concentration of 28 U/ml of TuM2Pk (95% percentile of normal healthy persons). Serum evaluation in 40 RCC showed a significant difference to healthy persons and a positive correlation with Robson stage and grading No correlation of TuM2Pk was found with histopathological cell type of tumor diameter. After radical nephrectomy normalization of TuM2Pk level was found within 11 weeks in all localized RCC. Continuously elevated serum levels were seen in metastatic RCC. Individual follow-up seems to be possible. CONCLUSION: Initial discrimination is not possible between localized and metastasized RCC using TuM2PK; however, it is possible to differentiate between benign and malignant renal processes; the specificity under these circumstances is 75%. After successful surgery of localized RCC, an elevated TuM2Pk will be normalized within 11 weeks, and will be remain elevated or will increase again in case of RCC-relapse or metastasis. Thus TuM2Pk would appear to be a useful marker for RCC detection and follow-up.

Antibodies, Monoclonal↗
PubMed2000

Anti-inflammatory activity of sodium pyruvate--a physiological antioxidant.

The anti-inflammatory activity of sodium pyruvate was evaluated in acute and chronic models of inflammation in rats. Oral administration of sodium pyruvate at three different dose levels of 125, 250 and 500 mg/kg body weight significantly inhibited the carrageenan induced acute paw edema in a dose dependent manner. The effect of 500 mg/kg sodium pyruvate was comparable to that of 12.5 mg/kg of standard diclofence. In Freund's adjuvant arthritis model, oral administration of sodium pyruvate at the submaximal dose of 250 mg/kg once daily upto one week before Freund's adjuvant injection and immediately by the same route on the 7th day of adjuvant injection significantly reduced the edema at 18 hours after the challenge. The treatment was continued for 14 days thereafter in two divided doses of 125 mg/kg in the morning and 125 mg/kg in the evening. Sodium pyruvate showed significant anti-inflammatory activity at the 14th day (chronic phase) also. To conclude, sodium pyruvate exhibited significant anti-inflammatory activity in both the models of inflammation which could be attributed to its antioxidant properties.

Animals↗
PubMed1999

[Evaluation of pyruvic acid concentration in blood of patients with ischemic stroke in the earliest stage of the disease].

The aim of the study was the assessment of concentrations of pyruvic acid in the blood of patients with mild course and severe course of ischaemic stroke in the earliest stage of the disease. The subject of the study were 20 patients with a mild ischaemic stroke and 20 patients with a severe one on its 1st, 3rd and 7th day. Enzymatic method for determining pyruvic acid content in the blood was used (ready made reagents Test-Combination Pyruvate by Boerhinger Mannheim). In the group of patients with mild ischaemic stroke the concentrations of pyruvic acid were increased on all days of the disease, compared with controls, but the differences were statistically insignificant. In the group of patients with severe ischaemic stroke the concentrations of pyruvic acid were higher than the ones in control group, but only on the 1st and 3rd day of the disease the differences were statistically significant. The results of determinations indicate that there is a positive correlation between levels of pyruvic acid and severity of the clinical course of the disease.

Cerebral Infarction↗
PubMed1979

Turnover of pegeon breast muscle pyruvate dehydrogenase complex.

The pigeon breast muscle pyruvate dehydrogenase complex was resolved into three component enzymes: lipoate acetyltransferase, pyruvate dehydrogenase, and lipoamide dehydrogenase. The antibodies against each component enzyme were prepared. All of the antibodies against component enzymes precipitated the pyruvate dehydrogenase complex. The enzyme complex was recovered as the immunoprecipitate from the extract of breast muscle of a pigeon that had received a single injection of L-[4,5-3H]leucine. The immunoprecipitate was separated into each component enzyme by SDS-polyacrylamide gel electrophoresis. The relative isotopic leucine incorporations per mg of protein into each component enzyme 4 h after the injection were 1.0 : 0.9 : 1.4 : 2.7 for lipoate acetyltransferase, alpha- and beta-subunit of pyruvate dehydrogenase, and lipoamide dehydrogenase, respectively. The half-lives of lipoate acetyltransferase, alpha- and beta-subunit of pyruvate dehydrogenase, and lipoamide dehydrogenase were 7.7, 2.5, 2.6, and 1.8 days, respectively. These results indicate that the component enzymes of the pyruvate dehydrogenase complex were synthesized and degraded at different rates.

Animals↗
PubMedDate not supplied

[Study of some properties of rat myocardial pyruvate kinase in adrenaline myocarditis].

Adrenaline myocarditis in rats was accompanied by a decrease in relative activity of pyruvate kinase from hyaloplasm of heart muscle, especially pronounced within 6-13 hrs after adrenaline administration. This phenomenon was probably due to an increase in content of protein in hyaloplasm, but not to an alteration in the enzyme activity. This conclusion was confirmed by studies of some properties of pyruvate kinase. Under these pathological conditions the Km of phosphoenol pyruvate was of the same order of magnitude as in normal state; 1-phenylalanine was characterized as an inhibitor of non-competitive type tomards phosphoenol pyruvate, and palmitate did not exhibit the inhibitory effect on pyruvate kinase as it was found in normal state. The effectiveness of the enzyme inhibition by L-phenylalanine, protection of the enzyme against this amino acid effect by L-alpha-alanine, L-serine and L-cysteine, and also the degree of activation of pyruvate kinase by the amino acids under adrenaline myocarditis were similar to those phenomena observed in normal state.

Amino Acids↗
PubMed2001

Protection by pyruvate against transient forebrain ischemia in rats.

Pyruvate has a remarkable protective effect against zinc neurotoxicity. Because zinc neurotoxicity is likely one of the key mechanisms of ischemic brain injury, the neuroprotective effect of pyruvate was tested in a rat model of transient forebrain ischemia. Control experiments in mouse cortical culture showed that pyruvate almost completely blocked zinc toxicity but did not attenuate calcium-overload neuronal death. Adult rats subjected to 12 min forebrain ischemia exhibited widespread zinc accumulation and neuronal death throughout hippocampus and cortex 72 hr after reperfusion. However, rats injected intraperitoneally with sodium pyruvate (500-1000 mg/kg) within 1 hr after 12 min forebrain ischemia showed almost no neuronal death. In addition, the mortality was markedly decreased in the pyruvate-protected groups (3.8%) compared with the NaCl-injected control group (58.1%). The neuroprotective effect persisted even at 30 d after the insult. The spectacular protection without noticeable side effects makes pyruvate a promising neuroprotectant in human ischemic stroke.

Animals↗
PubMed1975

The stereochemistry at carbon 3 of pyruvate lyase condensation products. 2-Keto-3-deoxygluconate-6-phosphate aldolase.

In a condensation between [3-3H3]pyruvate and D-glyceraldehyde-3-P as catalyzed by 2-keto-3-deoxygluconate-6-P aldolase (EC 4.1.2.14) of Pseudomonas putida, C--C synthesis occurred appreciably faster than C--3H bond breaking. Since tritium is present in tritiated pyruvate in tracer amounts, this result showed hydrogen isotope discrimination in pyruvate deprotonation and suggests enolpyruvate generation to be at least partially rate-limiting in the condensation reaction. Consequently, in a condensation reaction between [3-3H, 2H,H]pyruvate of known chirality and D-glyceraldehyde-3-P, the newly synthesized C--C bond would be enriched for at what was the C--H bond of chiral pyruvate, discriminating against the C--2H and C--3H bonds. Additional studies showed that condensations between (3S)-[3-3H, 2H,H]- or (3R)-[3-3H, 2H,H]pyruvate and D-glyceraldehyde-3-P yielded predominantly (3S)- or (3R)-2-keto-3-deoxy[3-3H, 2H]gluconate-6-P, respectively. By comparison with sterochemical models, it was concluded that condensation occurred with retention of configuration at C-3. Thus in the turnover of substrates as catalyzed by this enzyme, both the exchanging proton from water and D-glyceraldehyde-3-P attack the same face of the enzyme-bound pyruvyleneamine.

Aldehyde-Lyases↗