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PubMed2000

Seasonal change and prolonged anoxia affect the kinetic properties of phosphofructokinase and pyruvate kinase in oysters.

The effects of seasonal change, November versus July, and prolonged anoxia (96 h under N2 gas) on the properties of phosphofructokinase and pyruvate kinase from five tissues (gill, mantle, hepatopancreas, phasic adductor, catch adductor) of the oyster, Crassostrea virginica were investigated. Both enzymes showed tissue-specific and season-specific changes in kinetic properties; for pyruvate kinase this correlated with seasonal differences in enzyme elution patterns on hydroxylapatite chromatography. Kinetic properties of both enzymes in winter were consistent with primarily catabolic roles in glycolysis with responsiveness to cellular energy demands, whereas in summer these enzymes may be more closely regulated with respect to the biosynthetic and gluconeogenic functions of the tissues. Anoxia-induced changes in phosphofructokinase properties were relatively minor but anoxia stimulated changes in pyruvate kinase properties and elution profiles on hydroxylapatite in all tissues except mantle, with much greater effects seen for the enzyme from winter versus summer animals. For example, anoxia-induced changes in pyruvate kinase from winter gill included a fourfold rise in the substrate affinity constant for phosphoenolpyruvate, a sevenfold increase in the concentration of fructose-1,6-bisphosphate needed to activate the enzyme by 50%, and a 50% decrease in the concentration of L-alanine that inhibits activity by 50%. Changes in pyruvate kinase kinetics and hydroxylapatite elution patterns during prolonged anoxia are consistent with covalent modification of pyruvate kinase but contrary to results for many other mollusc species, anoxia exposure appears to induce a dephosphorylation of the enzyme.

Adaptation, Physiological↗
PubMed2003

Pyruvate decarboxylases from the petite-negative yeast Saccharomyces kluyveri.

Saccharomyces kluyveri is a petite-negative yeast, which is less prone to form ethanol under aerobic conditions than is S. cerevisiae. The first reaction on the route from pyruvate to ethanol is catalysed by pyruvate decarboxylase, and the differences observed between S. kluyveri and S. cerevisiae with respect to ethanol formation under aerobic conditions could be caused by differences in the regulation of this enzyme activity. We have identified and cloned three genes encoding functional pyruvate decarboxylase enzymes (PDCgenes) from the type strain of S. kluyveri (Sk- PDC11, Sk- PDC12 and Sk- PDC13). The regulation of pyruvate decarboxylase in S. kluyveri was studied by measuring the total level of Sk- PDC mRNA and the overall enzyme activity under various growth conditions. It was found that the level of Sk- PDC mRNA was enhanced by glucose and oxygen limitation, and that the level of enzyme activity was controlled by variations in the amount of mRNA. The mRNA level and the pyruvate decarboxylase activity responded to anaerobiosis and growth on different carbon sources in essentially the same fashion as in S. cerevisiae. This indicates that the difference in ethanol formation between these two yeasts is not due to differences in the regulation of pyruvate decarboxylase(s), but rather to differences in the regulation of the TCA cycle and the respiratory machinery. However, the PDC genes of Saccharomyces/ Kluyveromyces yeasts differ in their genetic organization and phylogenetic origin. While S. cerevisiae and S. kluyveri each have three PDC genes, these have apparently arisen by independent duplications and specializations in each of the two yeast lineages.

Aerobiosis↗
PubMed1984

Rat liver pyruvate kinase: influence of ligands on activity and fructose 1,6-bisphosphate binding.

The ability for various ligands to modulate the binding of fructose 1,6-bisphosphate (Fru-1,6-P2) with purified rat liver pyruvate kinase was examined. Binding of Fru-1,6-P2 with pyruvate kinase exhibits positive cooperativity, with maximum binding of 4 mol Fru-1,6-P2 per enzyme tetramer. The Hill coefficient (nH), and the concentration of Fru-1,6-P2 giving half-maximal binding [FBP]1/2, are influenced by several factors. In 150 mM Tris-HCl, 70 mM KCl, 11 mM MgSO4 at pH 7.4, [FBP]1/2 is 2.6 microM and nH is 2.7. Phosphoenolpyruvate and pyruvate enhance the binding of Fru-1,6-P2 by decreasing [FBP]1/2. ADP and ATP alone had little influence on Fru-1,6-P2 binding. However, the nucleotides antagonize the response elicited by pyruvate or phosphoenolpyruvate, suggesting that the competent enzyme substrate complex does not favor Fru-1,6-P2 binding. Phosphorylation of pyruvate kinase or the inclusion of alanine in the medium, two actions which inhibit the enzyme activity, result in diminished binding of low concentrations of Fru-1,6-P2 with the enzyme. These effectors do not alter the maximum binding capacity of the enzyme but rather they raise the concentrations of Fru-1,6-P2 needed for maximum binding. Phosphorylation also decreased the nH for Fru-1,6-P2 binding from 2.7 to 1.7. Pyruvate kinase activity is dependent on a divalent metal ion. Substituting Mn2+ for Mg2+ results in a 60% decrease in the maximum catalytic activity for the enzyme and decreases the concentration of phosphoenolpyruvate needed for half-maximal activity from 1 to 0.1 mM. As a consequence, Mn2+ stimulates activity at subsaturating concentrations of phosphoenolpyruvate, but inhibits at saturating concentrations of the substrate or in the presence of Fru-1,6-P2. Both Mg2+ and Mn2+ diminish binding of low concentrations of Fru-1,6-P2; however, the concentrations of the metal ions needed to influence Fru-1,6-P2 binding exceed those needed to support catalytic activity.

Alanine↗
PubMed1987

Hormonal regulation of L-type pyruvate kinase in rat liver cells in culture.

An immortalized rat liver cell line (RLC) expresses two isozymes of pyruvate kinase, the adult liver or L-type isozyme and an M-type isozyme presumed to be the M2-type. In RLC cells incubated in serum-free medium, the addition of 0.1 microM insulin maintained the initial level of L-type pyruvate kinase when it was high and induced the L-type isozyme when it was low. The addition of 1.0 mM dibutyryl cAMP and 0.5 mM theophylline decreased the L-type isozyme, even in the presence of insulin. The amount of M2-type isozyme was relatively constant under the conditions used. Regulation of the amount of L-type pyruvate kinase by both insulin and cAMP occurred primarily through changes in the rate of L-pyruvate kinase protein synthesis and translatable mRNA levels. These results are consistent with the in vivo observations that both insulin and glucagon regulate the rate of L-pyruvate kinase gene transcription and that cAMP is the dominant regulator of L-pyruvate kinase gene expression.

Animals↗
PubMed1987

"Stable" effects of insulin and isoproterenol on adipocyte pyruvate dehydrogenase.

Insulin, at a concentration of 1 mU/ml, stimulated glycogen synthase and pyruvate dehydrogenase about threefold in isolated rat adipocytes. Upon the removal of insulin, glycogen synthase activity remained in the activated state for 10 min and thereafter rapidly returned to basal level. On the other hand, insulin-stimulated pyruvate dehydrogenase activity remained elevated for at least 30 min. Isoproterenol (10(-8) M) stimulated phosphorylase and inhibited pyruvate dehydrogenase through the activation of beta-adrenergic receptors. Addition of the beta-antagonist, propranolol (10(-5) M), after isoproterenol reversed the action of isoproterenol on phosphorylase but not its action on pyruvate dehydrogenase. Dibutyryl cyclic AMP, when added to intact adipocytes, produced an effect on pyruvate dehydrogenase similar to that induced by isoproterenol. Our results indicate that both insulin and the beta-agonist have a unique action on pyruvate dehydrogenase which is different from their effects on other enzymes such as glycogen synthase and phosphorylase.

Adipose Tissue↗
PubMed1989

Pyruvate kinase isozymes from the green alga, Selenastrum minutum. I. Purification and physical and immunological characterization.

Pyruvate kinase from the green alga Selenastrum minutum consists of two isoforms (PK1 and PK2) separable by Q-Sepharose chromatography. The two isoforms have been highly purified to respective final specific activities of 42 and 23 (mumol pyruvate produced/min)/mg protein. Purification steps included salt fractionation, anion-exchange, hydrophobic interaction, and gel filtration chromatography. The final enzyme preparations differ significantly in physical and immunological properties. PK1 is heat labile and is completely inactivated following reaction with N-ethylmaleimide. In contrast, PK2 is heat-stable and is only partially inactivated following N-ethylmaleimide treatment. PK1 appears to be homotetrameric with a native molecular mass of about 240 kDa, whereas PK2 appears to be homodecameric with a native molecular mass of approximately 590 kDa. The antigenic reaction of both final PK preparations to rabbit antiserum prepared against homogeneous germinating castor bean endosperm cytosolic pyruvate kinase was tested by immunoprecipitation and Western blotting. The two algal pyruvate kinases are immunologically unrelated as only PK2 cross-reacts with the cytosolic pyruvate kinase antibodies. These data indicate that the S. minutum pyruvate kinase isoforms, PK1 and PK2, are not interconvertible forms of the same protein, but probably represent chloroplastic and cytosolic isozymes, respectively.

Ammonium Sulfate↗
PubMed1989

Independent regulation of pyruvate kinase expression by cyclic AMP and prostaglandin F2 alpha in mouse mastocytoma cells.

P-815 mouse mastocytoma cells express the K isozyme of pyruvate kinase and the specific activity of this enzyme is increased in response to N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate, 8-bromoadenosine 3':5'-cyclic monophosphate, cholera toxin, and epinephrine, all of which also elevate the intracellular concentration of adenosine 3':5'-cyclic monophosphate. Prostaglandin F2 alpha also increases the cellular activity of this enzyme, but does not increase the adenosine 3':5'-cyclic monophosphate levels. Under all these conditions, the increase in enzymatic activity is accompanied by an equivalent increase in the pyruvate kinase protein level. However, neither the rate of enzyme synthesis nor the level of pyruvate kinase mRNA is elevated by N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate. On the other hand, it does increase the enzyme's half-life. In contrast, prostaglandin F2 alpha increases the rate of synthesis and the level of pyruvate kinase K mRNA, but has no influence on the rate of degradation. Therefore, these cells have two mechanisms which increase pyruvate kinase K levels. One operates via an increase in cAMP level and results in a decrease in the rate of degradation, whereas the other minimizes an upsurge in cAMP levels but still increases pyruvate kinase K activity by increasing its rate of synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1975

Difference in pyruvate kinase regulation among three groups of yeasts.

Yeast pyruvate kinase (ATP : pyruvate 2-O-phosphotransferase EC 2.7.1.40) was classified into three groups based on the interaction with fructose-1,6-bisphosphate. The pyruvate kinases of Saccharomyces cerevisiae and Saccharomyces carlsbergensis were activated by fructose 1,6-bisphosphate in the concentration range tested (up to 10 mM) of the substrate, phosphoenolpyruvate; the enzymes of "fermentative Candida" (Candida tropicalis and Candida utilis) were affected by fructose 1,6-biphosphate only when the substrate concentration was below 2 mM. Although the pyruvate kinase of Candida lipolytica (a yeast belonging to "oxidative Candida") was also affected by fructose 1,6-bisphosphate, the degree of the activation was extremely small as compared with the above four yeasts. The pyruvate kinase of C. tropicalis was inhibited by ATP more strongly in the absence of fructose 1,6-bisphosphate than its presence. In the case of the C. lipolytica enzyme, however, the enzyme was inhibited to a lesser extent by ATP, and fructose 1,6-bisphosphate did not reverse the inhibitory effect of ATP. Time course changes of the enzyme levels in the yeasts grown on glucose and on ethanol indicate that the pyruvate kinases of S. cerevisiae and C. tropicalis can be controlled both by an allosteric mechanism and by changes in the enzyme concentration, although a marked difference was observed in the susceptibility to the allosteric effect by fructose 1,6-biphosphate between these fermentative yeasts. On the other hand, that of C. lipolytica would be controlled only by the latter mechanism.

Adenosine Triphosphate↗
PubMed1976

L-type pyruvate kinase from human liver. Purification by double affinity elution, electrofocusing and immunological studies.

L-type pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) was highly purified from adult human liver. This purification included ammonium sulphate fractionation, DEAE-Sephadex batchwise absorption and two CM-Sephadex chromatographies with selective elution by ligands; in the former chromatography pyruvate kinase was eluted by ATP, in the latter one by phosphoenolpyruvate and fructose 1,6-diphosphate. The last step of the purification procedure involved a hydroxyapatite column chromatography. This purification procedure allowed us to obtain 3.6 mg of protein with a specific activity 190 I.U./mg, i.e. a 1200-fold purification with an overall yield of about 8%. This preparation was homogenous as judged by immunodiffusion, acrylamide and sodium dodecyl sulphate acrylamide gel electrophoresis. Anti L-type pyruvate kinase antibodies were obtained from rabbits and the antigenic properties of L-type pyruvate kinase were studied. The enzyme appeared to be a tetramer (molecular weight 220 000-240 000) with subunits of similar molecular weight about 60 000). Two interconvertible major forms were found by isoelectrofocusing in a sucrose gradient and in an acrylamide slab gel: one had an isoelectric point of 5.85 +/- 0.09 and was the major enzymatic form after incubation with fructose 1,6-diphosphate or high concentrations or SH reagents. The other form (isoelectric point 6.28 +/- 0.03) was the major form of L-type pyruvate kinase in liver crude extract, and after incubation of purified enzyme with a proteic fraction isolated from liver extract by ammonium sulphate precipitation.

Chromatography, Affinity↗
PubMed1993

Pyruvate stimulates hormonal induction of lipogenic enzymes in primary cultured rat hepatocytes.

Hormonal inductions of lipogenic enzyme activities (fatty acid synthetase, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and ATP-citrate lyase) were studied in primary cultured rat hepatocytes. Insulin, triiodothyronine and dexamethasone markedly stimulated the inductions of the enzymes (particularly G6PD and ME) in the presence of pyruvate. Lactate also induced their activities. The activities of these enzymes in the presence of appropriate hormone combinations and a substrate amount of pyruvate were as high as, or higher than those in the liver of rats on high-carbohydrate, low-fat diet. The aldolase and glucokinase activities induced by these hormones were not enhanced by the addition of pyruvate. The induction by pyruvate was inhibited by actinomycin D or cycloheximide. The ATP content of rat hepatocytes was maintained without increase during culture with pyruvate for 6 days. These results indicate that the additions of pyruvate, or its metabolites to cultures of isolated hepatocytes have specific effects on the inductions of certain hepatic enzymes, possibly acting at the level of transcription. Their effects are similar to those of feeding a high-carbohydrate, low-fat diet to intact animals.

ATP Citrate (pro-S)-Lyase↗
PubMed1978

Proteolytic modification of pig and rat liver pyruvate kinase type L including phosphorylatable site.

The phosphorylated or phosphate-accepting site of pyruvate kinase from pig and rat liver was removed without inactivation by incubation with subtilisin. At different time intervals the subtilisin was inactivated with phenylmethylsulfonyl fluoride and the amount of remaining phosphorylatable or phosphorylated sites of pyruvate kinase estimated by incubation with an excess of [32P]-ATP and protein kinase. It was found that to get the same rate of modification the subtilisin concentration required to modify unphosphorylated pyruvate kinase was approximately ten times higher than that used for removal of the phosphorylated site of phosphorylated site of phosphorylated enzyme. It was shown that the proteolytically-modified pyruvate kinase had an increased apparent Km for phosphoenolpyruvate without a change in V, when compared to unmodified unphosphorylated and phosphorylated pyruvate kinase. The removal of the phosphorylated site was not associated with loss of the allosteric sites for ATP and Fru-1,6-P2. The possibility that phosphorylation of the pyruvate kinase increases its degradation rate in vivo is briefly discussed.

Adenosine Triphosphate↗
PubMed1983

Pyruvate decarboxylating activity in extracts from pigeon liver acetone powder.

Extracts of pigeon liver acetone powder showed, by a radiochemical method, considerable pyruvate decarboxylating activity. The 10-30% saturated ammonium sulfate fraction of these extracts required the addition of CoA, NAD+, and TPP for maximum pyruvate decarboxylating activity and presumably contained the pyruvate dehydrogenase complex (PDHC). The activity in the 40-60% saturated ammonium sulfate fraction had no requirement for CoA and/or NAD+ but had an absolute requirement for TPP. In similar preparations obtained from fresh pigeon liver, the PDHC activity was found in the 0-30% saturated ammonium sulfate fraction and only a small amount of pyruvate decarboxylating activity (independent of CoA and NAD+) was found in the 40-60% saturated ammonium sulfate fraction. The pyruvate decarboxylating activity which is found in the 40-60% saturated ammonium sulfate fraction of these extracts and has an absolute requirement for TPP, may represent pyruvate dehydrogenase (E1, EC 1.2.4.1), probably derived from PDHC by the acetone treatment at pH 7.8, or aging of the preparation.

Acetyltransferases↗
PubMed1977

Pyruvate kinase: diagnostic value in neuromuscular disease.

Pyruvate kinase activity was examined in the sera of a group of patients with neuromuscular disease and in carriers, and compared with that of creatine kinase. The following observations were made: 1. Pyruvate kinase activity was elevated in all 14 patients with Duchenne muscular dystrophy, with very high values generally correlating inversely with age or disease duration. Elevated values of pyruvate kinase were usually, but not invariably, associated with elevated values of creatine kinase. 2. Almost all patients with other muscle diseases and those with neural atrophy had modest elevations in pyruvate kinase activity. 3. ten of 17 individuals were identified as carriers of muscle disease by using both pyruvate kinase and creatine kinase while eight and nine, respectively, were detected using either assay alone. 4. When frozen stored EDTA-plasma was used for pyruvate kinase estimation, higher levels, as compared with the corresponding sera or fresh plasma, were found in controls and carriers but not in Duchenne muscular dystrophy patients. Frozen stored EDTA-plasma should, therefore, not be used for diagnostic purposes.

Adolescent↗
PubMed1977

Rapid diagnosis of pyruvate and ketoglutarate dehydrogenase deficiencies in platelet-enriched preparations from blood.

Radiochemical methods are described in detail to measure the activities of the pyruvate dehydrogenase complex and of the ketoglutarate dehydrogenase complex in platelet-enriched fractions. Determinations can be completed in one day with as little as 5 ml of venous blood. Activities are proportional to the length of the incubation and the amount of tissue protein added, show appropriate dependence on added cofactors, are stable for up to 2 days at -20 degrees C, and do not appear to be affected by diet. The pyruvate dehydrogenase complex appears to be fully activated (dephosphorylated) in these preparations. Activities were comparable in platelet-enriched fractions from 25 normal subjects and 25 patients with a variety of neurological and psychiatric diagnoses. Mean values (+/- S.E.M.) for these 50 individuals were 169+/-9 pmol/min per mg protein for the pyruvate dehydrogenase complex and 535+/-27 pmol/min per mg protein for the ketoglutarate dehydrogenase complex. These values are comparable to those found in cultured skin fibroblast with similar techniques. Deficient pyruvate dehydrogenase activity (19+/-6 and 11+/-4 pmol/min per mg protein) was demonstrated in platelet-enriched preparations from two brothers whose fibroblasts had previously been shown to be deficient in pyruvate dehydrogenase and who responed to a ketogenic diet. Experimental detail critical to obtaining reproducible results with these methods are stressed (notably the crucial importance of maintaining the purity of the radioactive substrates). These techniques allow identification of patients with pyruvate dehydrogenase deficiencies within one day without requiring liver or muscle biopsy.

Adolescent↗
PubMed1983

Effects of increased cardiac work on pyruvate dehydrogenase activity in hearts from diabetic animals.

The effects of increased cardiac work and availability of pyruvate on the activation of pyruvate dehydrogenase (PDH) was studied in hearts isolated from diabetic rats. Diabetes resulted in complete inactivation of myocardial PDH. At low levels of cardiac work, PDH in hearts perfused with glucose or glucose plus insulin as substrate remained in the inactive form even after 25 min of in vitro perfusion indicating that the factors causing inactivation in the diabetic animal were not easily reversed in vitro. Raising the level of ventricular pressure development from 60 to 180 mmHg caused only a small increase in the percent of active PDH (from 0.3 to 16%). Comparable values in control hearts were 61 and 96% active PDH. Addition of high levels of perfusate pyruvate along with glucose increased the percent active PDH from 0.3 to 45 at 60 mmHg ventricular pressure. Although pyruvate increased active PDH the effect was much less than in normal hearts (85% active under comparable conditions). Increased ventricular pressure development (180 mmHg) in diabetic hearts receiving pyruvate caused a further activation of PDH to 66% but again this effect was much less than occurred in normal hearts (96% active). Inactivation of PDH in hearts from diabetic animals could not be accounted for by high mitochondrial levels of known effectors such as NADH/NAD, acetyl CoA/CoA and ATP/ADP. Increasing cardiac work resulted in decreased mitochondrial levels of NADH, acetyl CoA and ATP, but these changes had little effect on PDH activity. The date indicate that PDH in hearts of diabetic animals is resistant to activation by increased cardiac work and high tissue levels of pyruvate.

Adenine Nucleotides↗
PubMed1991

Fatty acid accumulation during ischemia and reperfusion: effects of pyruvate and POCA, a carnitine palmitoyltransferase I inhibitor.

The present study was designed to evaluate the effects of POCA, a carnitine palmitoyltransferase I (CPT I) inhibitor, and pyruvate, a substrate inhibiting fatty acid (FA) oxidation, on post-ischemic cardiac FA accumulation on the one hand, and hemodynamic recovery and loss of cellular integrity on the other. To this end isolated, working rat hearts, receiving glucose (11 mM) as substrate, were subjected to 45 min of no-flow ischemia and 30 min of reperfusion. Hearts were perfused with or without POCA (10 microM) and/or pyruvate (5 mM). In the control group the FA content increased significantly during ischemia and remained elevated during reperfusion. Administration of POCA did not affect functional recovery and LDH release significantly, but resulted in about two-fold increased FA levels upon reperfusion as compared to glucose-perfused hearts. Pyruvate markedly improved functional recovery. Addition of this substrate did not affect lactate dehydrogenase (LDH) release, but enhanced FA accumulation during reperfusion. The combined administration of pyruvate and POCA nullified the positive effect of pyruvate on hemodynamic recovery, aggravated LDH release, and further enhanced the accumulation of FAs. The adenine nucleotide content of reperfused hearts was comparable for all groups investigated. In conclusion, during transient ischemia POCA and pyruvate markedly increased cardiac FA accumulation through inhibition of the oxidation of FAs released from endogenous lipid pools. No clear relation was found between the FA content of reperfused hearts and post-ischemic functional recovery.

Adenine Nucleotides↗
PubMed1976

Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women.

A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.

Adult↗
PubMed1996

The hormonal regulation of pyruvate dehydrogenase complex.

The pyruvate dehydrogenase complex has a central role in the regulation of mammalian metabolism as it represents the point-of-no-return in the utilization of carbohydrate. This article summarizes our studies into how signalling systems initiated by hormones binding to cell surface receptors can reach the pyruvate dehydrogenase system which is located within the inner mitochondrial membrane. One class of hormones which activate pyruvate dehydrogenase are those that increase cytoplasmic Ca2+. A wide range of studies on isolated enzymes, separated mitochondria and intact cell preparations have shown that the activation is due to the stimulation of pyruvate dehydrogenase phosphatase. Two other intramitochondrial dehydrogenases which regulate the citrate acid cycle are activated in parallel and this is an important means of balancing the supply of ATP to increasing cell demand. Insulin is also able to activate pyruvate dehydrogenase, but this is restricted to fat and other cells capable of lipogenesis. Insulin acts by stimulating pyruvate dehydrogenase phosphatase, but the activation does not involve alterations in Ca2+. The signalling pathway involved has not been established, but it appears to be quite distinct from those involved in many other actions of insulin.

Acetyl-CoA Carboxylase↗