Oxidation of 2-oxoisocaproate and 2-oxoisovalerate by the perfused rat heart. Interactions with fatty acid oxidation

1990 ◽  
Vol 68 (1) ◽  
pp. 260-265 ◽  
Author(s):  
Joan Letto ◽  
John T. Brosnan ◽  
Margaret E. Brosnan
Keyword(s):  
Amino Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Branched Chain Amino Acids ◽  
Acid Oxidation ◽  
Perfused Heart ◽  
Acid Dehydrogenase ◽  
Liver And Kidney ◽  
Labelled Compound ◽  
Branched Chain

The interactions between fatty acid oxidation and the oxidation of the 2-oxo acids of the branched chain amino acids were studied in the isolated Langendorff-perfused heart. 2-Oxoisocaproate inhibited the oxidation of oleate, but 2-oxoisovalerate and 2-oxo-3-methylvalerate did not. This difference was not attributable to the magnitude of the flux through the branched chain 2-oxo acid dehydrogenase, which was slightly higher with 2-oxoisovalerate than with 2-oxoisocaproate. Oxidation of 2-oxoisocaproate in the perfused heart was virtually complete, since more than 80% of the isovaleryl-CoA formed from 2-oxo[1-14C]isocaproate was further metabolized to CO2, as determined by comparing 14CO2 production from 2-oxo[14C(U)]isocaproate with that from the 1-14C-labelled compound. Only twice as much 14CO2 was produced from 2-oxo[14C(U)]isovalerate as from the 1-14C-labelled compound, indicating incomplete oxidation. This was confirmed by the accumulation in the perfusion medium of substantial quantities of labelled 3-hydroxyisobutyrate (an intermediate in the pathway of valine catabolism), when hearts were perfused with 2-oxo[14C(U)]isovalerate. The failure of 2-oxoisovalerate to inhibit fatty acid oxidation, then, can be attributed to the fact that its partial metabolism in the heart produces little ATP. We have previously shown that 3-hydroxyisobutyrate is a good gluconeogenic substrate in liver and kidney, and postulate that 3-hydroxyisobutyrate serves as an interorgan metabolite such that valine can serve as a glucogenic amino acid, even when its catabolism proceeds beyond the irreversible 2-oxo acid dehydrogenase in muscle.Key words: branched chain amino acids, branched chain 2-oxoacids, perfused heart, fatty acid metabolism, 3 -hydroxyisobutyrate.

scholarly journals The Role of Skeletal Muscle in The Pathogenesis of Altered Concentrations of Branched-Chain Amino Acids (Valine, Leucine, and Isoleucine) in Liver Cirrhosis, Diabetes, and Other Diseases

2021 ◽  
pp. 293-305
Author(s):  
M Holeček
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Liver Cirrhosis ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Branched Chain Amino Acids ◽  
Acid Oxidation ◽  
Amino Group ◽  
Branched Chain

The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the pathogenesis of their decreased concentrations in liver cirrhosis, increased concentrations in diabetes, and nonspecific alterations in disorders with signs of systemic inflammatory response syndrome (SIRS), such as burn injury and sepsis. The main role of skeletal muscle in BCAA catabolism is due to its mass and high activity of BCAA aminotransferase, which is absent in the liver. Decreased BCAA levels in liver cirrhosis are due to increased use of the BCAA as a donor of amino group to α-ketoglutarate for synthesis of glutamate, which in muscles acts as a substrate for ammonia detoxification to glutamine. Increased BCAA levels in diabetes are due to alterations in glycolysis, citric acid cycle, and fatty acid oxidation. Decreased glycolysis and citric cycle activity impair BCAA transamination to branched-chain keto acids (BCKAs) due to decreased supply of amino group acceptors (α-ketoglutarate, pyruvate, and oxaloacetate); increased fatty acid oxidation inhibits flux of BCKA through BCKA dehydrogenase due to increased supply of NADH and acyl-CoAs. Alterations in BCAA levels in disorders with SIRS are inconsistent due to contradictory effects of SIRS on muscles. Specifically, increased proteolysis and insulin resistance tend to increase BCAA levels, whereas activation of BCKA dehydrogenase and glutamine synthesis tend to decrease BCAA levels. The studies are needed to elucidate the role of alterations in BCAA metabolism and the effects of BCAA supplementation on the outcomes of specific diseases.

Properties of Acetate Kinase Isozymes and a Branched-Chain Fatty Acid Kinase from a Spirochete

1982 ◽  
Vol 152 (1) ◽  
pp. 246-254
Author(s):  
Caroline S. Harwood ◽  
Ercole Canale-Parola
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Molecular Weight ◽  
Fatty Acid ◽  
Branched Chain Amino Acids ◽  
Chain Fatty Acid ◽  
Acetate Kinase ◽  
Nucleoside Triphosphate ◽  
Branched Chain ◽  
Chain Fatty Acids

Spirochete MA-2, which is anaerobic, ferments glucose, forming acetate as a major product. The spirochete also ferments (but does not utilize as growth substrates) small amounts of l -leucine, l -isoleucine, and l -valine, forming the branched-chain fatty acids isovalerate, 2-methylbutyrate, and isobutyrate, respectively, as end products. Energy generated through the fermentation of these amino acids is utilized to prolong cell survival under conditions of growth substrate starvation. A branched-chain fatty acid kinase and two acetate kinase isozymes were resolved from spirochete MA-2 cell extracts. Kinase activity was followed by measuring the formation of acyl phosphate from fatty acid and ATP. The branched-chain fatty acid kinase was active with isobutyrate, 2-methylbutyrate, isovalerate, butyrate, valerate, or propionate as a substrate but not with acetate as a substrate. The acetate kinase isozymes were active with acetate and propionate as substrates but not with longer-chain fatty acids as substrates. The acetate kinase isozymes and the branched-chain fatty acid kinase differed in nucleoside triphosphate and cation specificities. Each acetate kinase isozyme had an apparent molecular weight of approximately 125,000, whereas the branched-chain fatty acid kinase had a molecular weight of approximately 76,000. These results show that spirochete MA-2 synthesizes a branched-chain fatty acid kinase specific for leucine, isoleucine, and valine fermentation. It is likely that a phosphate branched-chain amino acids is also synthesized by spirochete MA-2. Thus, in spirochete MA-2, physiological mechanisms have evolved which serve specifically to generate maintenance energy from branched-chain amino acids.

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

1978 ◽  
Vol 234 (5) ◽  
pp. E494 ◽  
Author(s):  
H S Paul ◽  
S A Adibi
Keyword(s):  
Amino Acids ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Acid Oxidation ◽  
Acyltransferase Activity ◽  
Remarkable Effect ◽  
Carnitine Acyltransferase ◽  
Branched Chain Amino Acid ◽  
Branched Chain

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

scholarly journals ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis

Cell Reports ◽  
2017 ◽  
Vol 19 (9) ◽  
pp. 1794-1806 ◽  
Author(s):  
Diane DeZwaan-McCabe ◽  
Ryan D. Sheldon ◽  
Michelle C. Gorecki ◽  
Deng-Fu Guo ◽  
Erica R. Gansemer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Er Stress ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Liver Fatty Acid ◽  
Liver And Kidney

scholarly journals Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine

1985 ◽  
Vol 227 (2) ◽  
pp. 651-660 ◽  
Author(s):  
T W Stephens ◽  
A J Higgins ◽  
G A Cook ◽  
R A Harris
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Fatty Acid Oxidation ◽  
Carnitine Palmitoyltransferase ◽  
Partial Purification ◽  
Acid Oxidation ◽  
Branched Chain Amino Acid ◽  
Malonyl Coa ◽  
Carnitine Palmitoyltransferase I ◽  
Branched Chain

Oxfenicine [S-2-(4-hydroxyphenyl)glycine] is transaminated in heart and liver to 4-hydroxyphenylglyoxylate, an inhibitor of fatty acid oxidation shown in this study to act at the level of carnitine palmitoyltransferase I (EC 2.3.1.21). Oxfenicine was an effective inhibitor of fatty acid oxidation in heart, but not in liver. Tissue specificity of oxfenicine inhibition of fatty acid oxidation was due to greater oxfenicine transaminase activity in heart and to greater sensitivity of heart carnitine palmitoyltransferase I to inhibition by 4-hydroxyphenylglyoxylate [I50 (concentration giving 50% inhibition) of 11 and 510 microM for the enzymes of heart and liver mitochondria, respectively]. Branched-chain-amino-acid aminotransferase (isoenzyme I, EC 2.6.1.42) was responsible for the transamination of oxfenicine in heart. A positive correlation was found between the capacity of various tissues to transaminate oxfenicine and the known content of branched-chain-amino-acid aminotransferase in these tissues. Out of three observed liver oxfenicine aminotransferase activities, one may correspond to asparagine aminotransferase, but the major activity could not be identified by partial purification and characterization. As reported previously for malonyl-CoA inhibition of carnitine palmitoyltransferase I, 4-hydroxyphenylglyoxylate inhibition of this enzyme was found to be very pH-dependent. In striking contrast with the kinetics of malonyl-CoA inhibition, 4-hydroxyphenylglyoxylate inhibition was not affected by oleoyl-CoA concentration, but was partially reversed by increasing carnitine concentrations.

scholarly journals Branched-chain amino acid oxidation in relation to catabolic enzyme activities in rats given aprotein-free diet at different stages of development

1974 ◽  
Vol 32 (3) ◽  
pp. 615-623 ◽  
Author(s):  
R. D. Sketcher ◽  
W. P. T. James
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Female Rats ◽  
Acid Oxidation ◽  
Stages Of Development ◽  
Oxidation Rates ◽  
Acid Dehydrogenase ◽  
Stage Of Development ◽  
The Difference ◽  
Branched Chain

1. The capacity of animals to conserve branched-chain amino acids was assessed during 3 weeks on a protein-free (PF) diet in groups of female rats at three stages of development, i.e. at weaning (35 g), in a period of rapid growth (85 g) and at maturity (200 g).2. Leucine and valine oxidation was assessed by monitoring the evolution of 14CO2 from a tracer dose of the [1-14C]-labelled L-amino acid given intragastrically. Activities of the L-leucine:2-ketoglutarate aminotransferase (EC 2.6.1.6) and α-keto acid dehydrogenase enzymes in leucine and valine metabolism were also determined in muscle and liver at weekly intervals.3. All three groups of rats given a normal protein intake excreted the same proportion of the dose of labelled leucine and valine. In rats given PF diet there was a consistent reduction in 14CO2 output from both L-[1-14C]leucine and L-[1-14C]valine, but valine was not conserved as efficiently as leucine.4. Muscle dehydrogenase responded to a PF diet in all three groups of rats, but the most marked changes occurred in the youngest group. In addition, there was a decrease in hepatic dehydrogenase activities for leucine and valine catabolism in the weanling group; in older animals there was little change in the α-keto-isovalerate, but a consistent decrease in the activity of the α-keto-isocaproic acid dehydrogenase. The difference in the responsiveness of the dehydrogenases, therefore, matched the difference between leucine and valine oxidation rates in vivo.5. Weanling animals responded rather more efficiently than the older animals to the need to conserve amino acids and there was no evidence of a poorly developed system for adapting to PF intake at this early stage of development.6. Despite reduced catabolism of the amino acids, aminotransferase activities in liver and muscle rose in the first 1–2 weeks on a PF regimen. Aminotransferase activity as such is unlikely to control acid oxidation.

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