Transamination of branched-chain keto acids by isolated perfused rat kidney.

1978 ◽  
Vol 235 (1) ◽  
pp. E47
Author(s):  
W E Mitch ◽  
W Chan
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Branched Chain Amino Acid ◽  
Keto Acids ◽  
Perfused Rat Kidney ◽  
Branched Chain ◽  
Branched Chain Keto Acids ◽  
Isolated Rat

Isolated rat kidney perfused without substrate released serine, glycine, and taurine, and substantially smaller amounts of other amino acids. When branched-chain keto acids were added, the corresponding amino acids were released at rates amounting to 15-25% of keto acid disappearance. Perfusion with 2 mM alpha-keto-isovalerate or alpha-keto-beta-methylvalerate caused an increased glucose release amounting to 18-23% of keto acid disappearance. The activity of branched-chain amino acid transferase (BATase) was significantly stimulated by perfusion with the analogue of leucine, but not by perfusion with alpha-ketoglutarate, the analogues of valine or isoleucine, or with leucine itself. These findings document that the kidney converts branched-chain keto acids in part to the corresponding amino acids and suggest that the keto analogue of leucine may be involved in the control of renal BATase activity, thereby indirectly regulating the metabolism of branched-chain amino acids.

BLOOD BRANCHED-CHAIN AMINO AND α-KETO ACID CONCENTRATIONS AND NET EXCHANGE ACROSS THE PORTAL-DRAINED VISCERA AND HINDLIMB OF FED AND FASTED RUMINANTS

1987 ◽  
Vol 67 (4) ◽  
pp. 1011-1020 ◽  
Author(s):  
RICHARD J. EARLY ◽  
JAMES R. THOMPSON ◽  
ROBERT J. CHRISTOPHERSON ◽  
GARY W. SEDGWICK
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hind Limb ◽  
Venous Blood ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Branched Chain Amino Acid ◽  
Keto Acids ◽  
Branched Chain ◽  
Cattle And Sheep

In the first of two experiments, whole blood branched-chain amino acid (BCAA) and plasma branched-chain α-keto acid (BCKA) concentrations in jugular venous blood were determined in cattle and sheep before and during a 6-d fast. In cattle, concentrations of valine, isoleucine, α-ketoisovalerate (KIV) and α-ketomethylvalerate (KMV) remained unchanged whereas leucine and α-ketoisocaproate (KTC) increased (P < 0.05) during fasting. In sheep, only KIV and KMV remained unchanged whereas BCAA and KIC increased (P < 0.05) during fasting. In a second experiment on cattle chronically catheterized to measure BCAA and BCKA exchange across the portal-drained viscera (PDV) and hindlimb (HL), the PDV added and the HL removed BCAA from the blood of fed cattle. The opposite exchange occurred after a 6-d fast. Releases of BCKA from the PDV and HL in both fed and fasted states were small compared to BCAA exchanges. The data suggest that blood BCAA but not BCKA concentrations may respond differently to starvation in sheep versus cattle and that in cattle the PDV and HL do not release appreciable amounts of BCKA relative to the net movements of the BCAA. Key words: Portal-drained viscera, hind limb, branched-chain amino acids, branched-chain α-keto acids, fasting, ruminants

Influence of branched-chain amino acids and branched-chain keto acids on protein synthesis in isolated hepatocytes

Hepatology ◽  
1987 ◽  
Vol 7 (2) ◽  
pp. 324-329 ◽  
Author(s):  
Wolfgang Base ◽  
Carl Barsigian ◽  
Alisa Schaeffer ◽  
Ellen Shaw ◽  
Jose Martinez ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Isolated Hepatocytes ◽  
Branched Chain Amino Acids ◽  
Keto Acids ◽  
Branched Chain ◽  
Branched Chain Keto Acids

scholarly journals Branched-Chain Amino Acids and Branched-Chain Keto Acids in Hyperammonemic States: Metabolism and as Supplements

Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 324 ◽  
Author(s):  
Milan Holeček
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Muscle Performance ◽  
Strenuous Exercise ◽  
Protein Balance ◽  
Keto Acids ◽  
Amino Acid Imbalance ◽  
Branched Chain ◽  
Cycle Disorders ◽  
Branched Chain Keto Acids

In hyperammonemic states, such as liver cirrhosis, urea cycle disorders, and strenuous exercise, the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) is activated and BCAA concentrations decrease. In these conditions, BCAAs are recommended to improve mental functions, protein balance, and muscle performance. However, clinical trials have not demonstrated significant benefits of BCAA-containing supplements. It is hypothesized that, under hyperammonemic conditions, enhanced glutamine availability and decreased BCAA levels facilitate the amination of branched-chain keto acids (BCKAs; α-ketoisocaproate, α-keto-β-methylvalerate, and α-ketoisovalerate) to the corresponding BCAAs, and that BCKA supplementation may offer advantages over BCAAs. Studies examining the effects of ketoanalogues of amino acids have provided proof that subjects with hyperammonemia can effectively synthesize BCAAs from BCKAs. Unfortunately, the benefits of BCKA administration have not been clearly confirmed. The shortcoming of most reports is the use of mixtures intended for patients with renal insufficiency, which might be detrimental for patients with liver injury. It is concluded that (i) BCKA administration may decrease ammonia production, attenuate cataplerosis, correct amino acid imbalance, and improve protein balance and (ii) studies specifically investigating the effects of BCKA, without the interference of other ketoanalogues, are needed to complete the information essential for decisions regarding their suitability in hyperammonemic conditions.

Regulation of valine and alpha-ketoisocaproate metabolism in rat kidney mitochondria

1988 ◽  
Vol 255 (4) ◽  
pp. E475-E481 ◽  
Author(s):  
R. H. Miller ◽  
A. E. Harper
Keyword(s):  
Amino Acid ◽  
Rat Kidney ◽  
Co2 Evolution ◽  
Radioactive Tracers ◽  
Keto Acid ◽  
Kidney Mitochondria ◽  
Assay Medium ◽  
Branched Chain Amino Acid ◽  
Keto Acids ◽  
Branched Chain

Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and alpha-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids alpha-ketoisocaproate (KIC) or alpha-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of 14C-labeled products formed (14CO2 or [1-14C]-keto acid). Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, alpha-ketoglutarate (alpha-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM alpha-KG as the amino acceptor; these rates were 5- to 50-fold those without added alpha-KG. Rates of CO2 evolution from valine also increased when KIC (0.01-0.10 mM) was present; however, with KIC concentrations above 0.2 mM, rates of CO2 evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, alpha-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract MP125: Branched-chain Keto Acids, Not Branched-chain Amino Acids, Impairs Cardiac Insulin Sensitivity by Disrupting Insulin Signaling in the Mitochondria

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Qutuba Karwi ◽  
Golam Mezbah Uddin ◽  
Cory S Wagg ◽  
Gary D Lopaschuk
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Insulin Sensitivity ◽  
Glucose Oxidation ◽  
Branched Chain Amino Acids ◽  
Mitochondrial Translocation ◽  
Oxidation Rates ◽  
Keto Acids ◽  
Branched Chain ◽  
Branched Chain Keto Acids

Alterations in branched-chain amino acids (BCAA) oxidation have been linked to the development of cardiac insulin resistance and its negative impact on cardiac function. However, it is not clear if these detrimental effects are due to the accumulation of BCAAs or branched-chain keto acids (BCKAs). It is also unknown how impaired BCAAs oxidation mediates cardiac insulin resistance. To examine this, we specifically deleted mitochondrial branched-chain aminotransferase (BCATm) in the heart to selectively increase in BCAAs and decrease in BCKAs in the heart. BCATm -/- mice had normal cardiac function compared to their wildtype littermates (WT Cre+/+ ). However, there was a significant increase in insulin-stimulated cardiac glucose oxidation rates in BCATm -/- mice, independent of any changes in glucose uptake or glycolytic rates. This enhancement in cardiac insulin sensitivity was associated with an increase in the phosphorylation of Akt and activation of pyruvate dehydrogenase (PDH), the rate-limiting enzyme of glucose oxidation. To determine the impact of reversing these events, we examined the effects of increasing cardiac BCKAs on cardiac insulin sensitivity. We perfused isolated working mice hearts with high levels of BCKAs (α;-keto-isocaproate 80 μM, α;-keto-β;-methylvalorate 100μM, α;-keto-isovalorate 70 μM), levels that can be seen during diabetes and obesity. The BCKAs completely blunted insulin-stimulated glucose oxidation rates. We also found that BCKAs abolished insulin-stimulated mitochondrial translocation of Akt, an effect which was associated with PDH deactivation. We conclude that the accumulation of BCKAs, and not BCAAs, is a major contributor to cardiac insulin resistance via abrogating mitochondrial translocation of Akt.

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.

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