Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was prompted by the paradox of strong presence of mitochondria in an anaerobic protozoan, recently reclassified from the yeasts. Stemming from publication in 1911 to 1912, Blastocystis hominis has been generally accepted as a harmless intestinal yeast of humans, with short standardized textbook (parasitology) descriptions, even to the present day. Reports since 1967 have changed the classification of B. hominis from yeast to protozoan (Sarcodina), and this has been followed by interest in B. hominis-caused disease, resulting in documentation of disease in humans and other primates. In this study of B. hominis, the basic ultrastructure of the mitochondria was shown by thin-section electron microscopy to be identical to that of an archetypical mitochondrion. There were hundreds of them in large B. hominis cells (100 to 200 microns in diameter). Mitochondria were confined to a peripheral ring of cytoplasm bounded by the outer cell membrane (there is no cell wall) and the membrane of the large, spherical, organelle-free central body that constitutes 75% of the cell's volume. Mitochondria tended to surround the cell's usual two to four nuclei. Rhodamine 123 stained the mitochondria selectively, visualized by fluorescence microscopy. The cell was devoid of cytochromes. Addition of 0.1% cytochrome c to the growth medium increased utilization of glucose by 34% and that of lactate by 17%. Furthermore, it markedly increased the number of mitochondrion-filled cells. At higher concentrations, cytochrome c inhibited the growth of the cells. Despite the presence of large numbers of mitochondria, activities of the mitochondrial enzymes pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, isocitrate dehydrogenase, glutamate dehydrogenase, and cytochrome c oxidase were absent. Thus, the function of the mitochondria in B. hominis remains unknown. Considerable activities of aspartate aminotransferase and alanine aminotransferase were found. Aldolase activity was prominent. Pyruvate decarboxylase was present. Diaphorase and lactate dehydrogenase were detectable but in suspect quantities. Other missing enzymes were gamma glutamyl transpeptidase, alkaline phosphatase (a lysosomal marker), and creatine kinase isoenzymes.
 ...
PMID:Biochemical and ultrastructural study of Blastocystis hominis. 283 9

The activities of lipoyl dehydrogenase, aspartate transaminase, and alanine transaminase, and levels of lactate were estimated in cerebral cortex, cerebellum, and brainstem of rats intoxicated acutely with tetraethyl lead and chronically with lead acetate. A significant inhibition of lipoyl dehydrogenase was observed in both groups of animals, whereas transaminase activities were increased in inorganic lead toxicity. Oxidative decarboxylation and anaplerosis of pyruvate was assessed in brain slices using [1-14C]pyruvate. Pyruvate dehydrogenase activity was decreased in both organic and inorganic lead toxicity, whereas labelling of aspartate and alanine was increased in inorganic lead toxicity. In studies in vitro, lead acetate showed a more significant effect than tetraethyl lead. The higher anaerobic metabolism in inorganic lead toxicity, as evidenced by increased anaerobic lactate production by brain slices, could either be an adaptive mechanism or be due to the delayed maturation of brain in the developing rat. Such a mechanism does not occur in acute organic lead toxicity, as the compound brings about massive and rapid degenerative changes in brain, resulting in convulsive seizures and death of the animals.
 ...
PMID:Pyruvate metabolism in the brain of young rats intoxicated with organic and inorganic lead. 654 9

We tested the hypotheses that: (i) exercise with low muscle glycogen would reduce pyruvate flux through the alanine aminotransferase (AAT) reaction and attenuate the increase in tricarboxylic acid (TCA) cycle intermediates, and (ii) attenuation of tricarboxylic acid cycle intermediate (TCAI) pool expansion would limit TCA cycle flux, thereby accelerating phosphocreatine (PCr) degradation. Eight men cycled for 10 min at 70 % of their (VO(2,max) on two occasions: (i) following their normal diet (CON) and (ii) after cycling to exhaustion and consuming a low carbohydrate diet for approximately 2 days (LG). Biopsies (m. vastus lateralis) confirmed that [glycogen] was lower in LG vs. CON at rest (257 +/- 18 vs. 611 +/- 54 mmol (kg dry mass)(-1); P 0.05); however, net glycogenolysis was not different after 1 or 10 min of exercise. PCr degradation from rest to 1 min was approximately 26 % higher in LG vs. CON (38 +/- 4 vs. 28 +/- 4 mmol (kg dry mass)(-1); P< or =0.05). The sum of five measured TCAIs (approximately 90 % of total pool) was not different between trials at rest and after 1 min, but was higher after 10 min in LG vs. CON (5.51 +/- 0.43 vs. 4.45 +/- 0.49 mmol (kg dry mass)(-1); P 0.05). Pyruvate dehydrogenase complex (PDC) activity was lower during exercise in LG vs. CON (2.2 +/- 0.2 vs. 1.4 +/- 0.2 mmol min(-1) (kg wet weight)(-1) after 10 min; P< or =0.05), and acetylcarnitine was approximately threefold less, implying increased pyruvate availability for flux through AAT. Resting muscle [glutamate] was higher in LG vs. CON (16.1 +/- 0.8 vs. 11.8 +/- 0.4 mmol (kg dry mass)(-1); P< or =0.05) and the net decrease in [glutamate] during exercise was approximately 30 % greater in LG vs. CON. These findings suggest that: (i) contrary to our hypotheses, LG increased anaplerosis by decreasing PDC flux and/or increasing the conversion of glutamate carbon to TCAIs, and (ii) accelerating the rate of muscle TCAI expansion did not affect oxidative energy provision during the initial phase of contraction, since changes in [TCAI] were not temporally related to PCr degradation.
 ...
PMID:Exercise with low muscle glycogen augments TCA cycle anaplerosis but impairs oxidative energy provision in humans. 1198 92

Shc proteins interact with the insulin receptor, indicating a role in regulating glycolysis. To investigate this idea, the activities of key glycolytic regulatory enzymes and metabolites levels were measured in skeletal muscle from mice with low levels of Shc proteins (ShcKO) and wild-type (WT) controls. The activities of hexokinase, phosphofructokinase-1 and pyruvate kinase were decreased in ShcKO versus WT mice under both fed and fasted conditions. Increased alanine transaminase and branched-chain amino acid transaminase activities were also observed in ShcKO mice under both fed and fasting conditions. Protein expression of glycolytic enzymes was unchanged in the ShcKO and WT mice, indicating that decreased activities were not due to changes in their transcription. Changes in metabolite levels were consistent with the observed changes in enzyme activities. In particular, the levels of fructose-2,6-bisphosphate, a potent activator of phosphofructokinase-1, were consistently decreased in the ShcKO mice. Furthermore, the levels of lactate (inhibitor of hexokinase and phosphofructokinase-1) and citrate (inhibitor of phosphofructokinase-1 and pyruvate kinase) were increased in fed and fasted ShcKO versus WT mice. Pyruvate dehydrogenase activity was lower in ShcKO versus WT mice under fed conditions, and showed inhibition under fasting conditions in both ShcKO and WT mice, with ShcKO mice showing less inhibition than the WT mice. Pyruvate dehydrogenase kinase 4 levels were unchanged under fed conditions but were lower in the ShcKO mice under fasting conditions. These studies indicate that decreased levels of Shc proteins in skeletal muscle lead to a decreased glycolytic capacity in both fed and fasted states.
...
PMID:Key glycolytic enzyme activities of skeletal muscle are decreased under fed and fasted states in mice with knocked down levels of Shc proteins. 2588 Jun 38

Though mitochondrial oxidant stress plays a critical role in the progression of acetaminophen (APAP) overdose-induced liver damage, the influence of mitochondrial bioenergetics on this is not well characterized. This is important, since lifestyle and diet alter hepatic mitochondrial bioenergetics and an understanding of its effects on APAP-induced liver injury is clinically relevant. Pyruvate dehydrogenase (PDH) is critical to mitochondrial bioenergetics, since it controls the rate of generation of reducing equivalents driving respiration, and pyruvate dehydrogenase kinase 4 (PDK4) regulates (inhibits) PDH by phosphorylation. We examined APAP-induced liver injury in PDK4-deficient (PDK4-/-) mice, which would have constitutively active PDH and hence elevated flux through the mitochondrial electron transport chain. PDK4-/- mice showed significant protection against APAP-induced liver injury when compared to wild type (WT) mice as measured by ALT levels and histology. Deficiency of PDK4 did not alter APAP metabolism, with similar APAP-adduct levels in PDK4-/- and WT mice, and no difference in JNK activation and translocation to mitochondria. However, subsequent amplification of mitochondrial dysfunction with release of mitochondrial AIF, peroxynitrite formation and DNA fragmentation were prevented. Interestingly, APAP induced a rapid decline in UCP2 protein levels in PDK4-deficient mice. These data suggest that adaptive changes in mitochondrial bioenergetics induced by enhanced respiratory chain flux in PDK4-/- mice render them highly efficient in handling APAP-induced oxidant stress, probably through modulation of UCP2 levels. Further investigation of these specific adaptive mechanisms would provide better insight into the control exerted by mitochondrial bioenergetics on cellular responses to an APAP overdose.
 ...
PMID:Mice deficient in pyruvate dehydrogenase kinase 4 are protected against acetaminophen-induced hepatotoxicity. 3180 57