Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
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PMID:Myocardial metabolism and heart disease. 3 41

A reduction in myocardial oxygen supply during ischemia, not only leads to reduced aerobic ATP production but does not stimulate glycolytic ATP synthesis. The residual aerobically synthesized ATP comes primarily from continued inefficient (i.e., compared to glucose in terms of moles of ATP produced per mole of O2 consumed) oxidation of fatty acids. This leads to elevated tissue levels of long chain fatty acyl-CoA and fatty acyl-carnitine. Both are potentially cell damaging metabolic intermediates. Restriction of glycolysis is due to inhibition of glyceraldehyde-3-phosphate dehydrogenase by accumulated metabolites, such as H+, lactate and NADH. The reduced production of ATP leads to decreased levels of high energy phosphate stores which in turn may impair myocardial mechanical function.
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PMID:Energy metabolism in the ischemic heart. 55 21

1. The changes with the time of the activities of some energy-supplying enzymes and of the hydrolytic enzyme, acid phosphatase, were studied over 2 weeks of complete ischaemia, produced in the rat soleus muscle by section of the abdominal aorta and terminal devascularization, leaving nerve and tendon intact. 2. Activities of glycolytic enzymes, oxidative enzymes, hexokinase and acid phosphatase are affected in a different manner. Activities of the glycolytic enzymes, lactate dehydrogenase, triosephosphate dehydrogenase and glycerolphosphate dehydrogenase, are lowest on the 1st day and increase thereafter. The first two reach the control values again on the 4th and 14th day, respectively, while glycerolphosphate dehydrogenase reaches about 50% of the control value on the 14th day. The maximum decrease in activity of the oxidative enzymes, citrate synthase, beta-hydroxyacyl-CoA-dehydrogenase and malate dehydrogenase occurs later (4th day); thereafter their activity returns slowly to control values, but does not reach them even on the 14th day. Hexokinase activity is slightly decreased on the 1st day; then it increased and reached on the 7th day twice the control value. Thus on the 1st day the activity of the enzymes of aerobic metabolism prevail, and on the 4th day those of anaerobic carbohydrate (glucose) metabolism; the recovery of enzyme activity of aerobic oxidation occurs later. 3. Acid phosphatase activity increased from the 2nd day onwards, reaching up to 3 times the control value on the 4th day and still twice that value on the 14th day. This agrees well with the histochemical picture of acid phosphatase. 4. Histochemical changes of alkaline phosphatase activity reveal destruction of capillary endothelial cells during the first few days after operation and their later proliferation from the periphery, correlating with the loss and recovery of oxidative enzyme activity.
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PMID:Effects of ischaemia on enzyme-activities in the soleus muscle of the rat. 57 Nov 16

Control of glycolysis and fatty acid oxidation in ischemic myocardium was studied in isolated working rat hearts. Coronary flow was reduced to the whole heart. In ischemic tissue, oxygen consumption, glycolysis and fatty acid oxidation all decreased in proportion to the restriction in coronary flow. Inhibition of glycolysis developed at the level of glyceraldehyde-3-phosphate dehydrogenase. Restricted flux through this step appeared to result from accumulation of lactate, H+ and NADH. The rate of glycolysis was inversely related to accumulation of lactate. Additions of high levels of lactate to the perfusate inhibited glycolysis in aerobic, anoxic and ischemic hearts. The mechanism of this effect of lactate in anaerobic hearts is unknown, but does not appear to be related to pH changes. Oxidation of fatty acids was restricted at the level of beta-oxidation and high levels of both long-chain acyl CoA and carnitine derivatives accumulated.
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PMID:Rate-limiting steps of carbohydrate and fatty acid metabolism in ischemic hearts. 106 35

1. The following enzyme activities were estimated in needle-biopsy samples of the lateral part of the human quadriceps femoris muscle: triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), NAD : glycerol-3-phosphate dehydrogenase (GPDH), hexokinase (HK), NAD: malate dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase. 2. Although the enzyme activities in muscles of women were lesser than in those of men, no difference was found in the calculated enzyme activity ratios. There is thus no sex-dependent metabolic type-differentiation in this muscle. 3. The human quadriceps femoris is a low-activity muscle, in comparison with muscles of homoiotherm laboratory animals. The enzyme activity ratio of TPDH to CS, characterizing the glycolytic pyruvate formation to aerobic oxidative capacities, shows this muscle to be of an intermediate type in this respect, similarly as the extensor digitorum longus of the rat. The relatively very high capacity of glucose phosphorylation (HK), the high aerobic regeneration of cytoplasmic dehydrogenated NAD (GPDH) and the very low anaerobic regeneration (LDH), show the unusually high proportion of carbohydrates (glucose) which can be broken down aerobically.
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PMID:M. Quadriceps femoris of man, a muscle with an unusual enzyme activity pattern of energy supplying metabolism in mammals. 116 80

1. In biopsy samples of the lateral part of m. quadriceps femoris of 49 obese and 14 lean persons the activities of the following enzymes were investigated: triosephosphate dehydrogenase (TPDH), glycerolphosphate: nad dehydrogenase (GPDH), lactate dehydrogenase (LDH), hexokinase (HK), malate: NAD dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOADH). 2. The muscles of obese had an increased activity ratio of TPDH to CS and to HK, respectively, caused in muscles of female obese subjects by an increase of TPDH activity, in those of obese men rather by a decrease of CS and HK activities. 3. Cluster analysis brough to light the existence of three major groups. Group 1 (low activity-low LDH group), consisting of muscles of female obese subjects only, exhibited low activities of all enzymes investigated, that of LDH being so low as to possibly induce a serious deficiency of anerobic metabolism under working conditions. Group 2 (medium enzyme activity group) was characterized by medium enzyme activities, similar to that of lean controls (included in this group). This consisted of subjects of both sex. Group 3 (high enzyme activity group) consisted of obese of both sex. It was distinguished by high enzyme activities, especially of LDH. It is suggested that the groups of similar enzyme activity patterns might reflect different stages, types and/or genesis of obesity.
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PMID:Metabolic changes in the quadriceps femoris muscle of obese people. Enzyme activity patterns of energy-supplying metabolism. 123 24

Hexanoate and octanoate inhibit the triiodothyronine (T3)-induced increases in the activities of malic enzyme and fatty acid synthase in chick embryo hepatocytes in culture. Butanoate was less effective as an inhibitor, and palmitate, stearate, and oleate had no effect or small stimulatory effects. Hexanoate and octanoate inhibited the lipogenic enzyme activities at a transcriptional step, and did so within 30 min of addition. Incubation for 2 h in the absence of fatty acid reversed the inhibition of transcription caused by hexanoate. The inhibitory effect of hexanoate was selective because DNA content and transcription of the glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes were not inhibited. Hexanoate-mediated inhibition of transcription rates of the lipogenic genes was not correlated with an inhibition of binding of T3 to its nuclear receptor. 2-Bromooctanoate and carnitine stimulated the T3-induced accumulation of the mRNAs for malic enzyme and fatty acid synthase. The presence of hexanoate stimulated by 2- to 3-fold the increase caused by carnitine, suggesting that hexanoate and carnitine may regulate lipogenic gene expression by a common pathway. Hexanedioate, acetoacetate, beta-hydroxybutyrate, branched chain fatty acids, and branched chain keto acids had little or no effect on abundance of the lipogenic mRNAs. We suggest that the active inhibitor is a metabolite derived from hexanoate or octanoate, possibly an intermediate derived from an acyl-CoA derivative.
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PMID:Hexanoate and octanoate inhibit transcription of the malic enzyme and fatty acid synthase genes in chick embryo hepatocytes in culture. 163 32

To determine whether respiratory muscles undergo alterations in enzyme activities of energy metabolism as a result of increased mechanical activity, adult male Wistar rats were subjected to a prolonged endurance training program. Analysis off maximal enzyme activity patterns in the diaphragm following 15 weeks of extreme training (final running duration: 210 min per day, 27 m.min-1 at 15 degrees grade, indicated significant reductions in the marker enzymes of the citric acid cycle (citrate synthase), glycolysis (pyruvate kinase, PK; lactate dehydrogenase, LDH), ketone body utilization (3-keto acid: CoA transferase) and transamination (glutamate pyruvate transaminase, GPT). No changes were found for the enzymes of glycogenolysis (phosphorylase, PHOSPH), glycolysis (glyceraldehyde phosphate dehydrogenase, GAPDH), glucose phosphorylation (hexokinase, HK) and beta-oxidation (3-hydroxyacyl: CoA dehydrogenase, HAD) following training. In contrast, in the external intercostal muscle, increases in the range of 57-77% were noted for the enzymes CS and HAD, whereas in the internal intercostal muscles no training induced alteration was evident for these enzymes. For both the intercostal muscles, a consistent trend was noted towards a reduction in all of the glycolytic enzymes investigated, however, significantly lower values were recorded for only PK and LDH in the internal intercostals. GPT was increased in the internal intercostal muscles. These findings indicate that the response pattern observed in the enzyme activities studied following training are to some degree specific to the respiratory muscle investigated.
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PMID:Differential response of enzyme activities in rat diaphragm and intercostal muscles to exercise training. 337 43

Thirty-six biopsy specimens of human biceps and vastus lateralis muscles were examined by histometric analysis and determination of enzyme activities (phosphorylase, triosephosphate dehydrogenase, 3-hydroxacyl-CoA-dehydrogenase, lactate dehydrogenase, hexose isomerase, citrate synthetase, 6-phosphogluconate dehydrogenase). The series included 13 specimens from patients suffering from a benign form of muscular dystrophy (limb girdle and Becker type of muscular dystrophy) and 12 specimens from patients with an acute (n = 5) or chronic (n = 7) form of myositis. Muscle fibres were atrophic in myositis and hypertrophic (with an increased variation of fibre diameters) in muscular dystrophies, as has been shown previously. When myositis samples were compared with either normal or dystrophic muscles, a highly significant lowering of glycolytic enzyme activity was found in chronic myositis, while the activity of 6-phosphogluconate dehydrogenase was elevated to highly significant levels. Measurements of the latter enzyme's activity might be of additional value in differentiating chronic forms of myositis from benign muscular dystrophies.
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PMID:Additional biochemical criteria in the differential diagnosis of myositis. 343 Jan 87

We determined representative enzyme activities of glycogenolysis (glycogen phosphorylase) glycolysis (d-glyceraldehyde-3-phosphate dehydrogenase, GAPDH), beta oxidation of free fatty acids (1-3-hydroxyacyl CoA dehydrogenase, HADH), citric acid cycle (citrate synthase, CS), lactate fermentation (lactate dehydrogenase LDH), and creatine phosphate metabolism (creatine kinase, CK) in left ventricular samples of 36 patients to investigate if the metabolic capacities of the energy-supplying pathways are differently affected in different heart diseases. There were 17 patients with mitral valve diseases (MVD), 8 patients with aortic valve diseases (AVD), and 11 patients who suffered from dilative cardiomyopathies (DCM). The main metabolic characteristic on the level of enzymatic organization in patients with DCM was an increased ratio of GAPDH/HADH activities and a decreased ratio of HADH/CS activities compared to the valve-diseased patients. This result indicates that the capacity of glucose oxidation is enhanced at the expense of fatty acid metabolism in patients with DCM. Furthermore, we determined significantly lower myocardial CK activities in this group of patients, most probably reflecting a diminished content of myofibrils. Citrate synthase activity was lowest in patients with AVD. Although we cannot rule out that the impaired left ventricular function is in part responsible for the shift of the capacities of the energy-supplying metabolism in patients with DCM, we favor the assumption that it is a specific feature of this myocardial disease.
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PMID:Comparative analysis of myocardial enzyme activities of the energy-supplying metabolism in patients with dilative cardiomyopathies and valve diseases. 370 46


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