Divergent Induction of Branched-Chain Aminotransferases and Phosphorylation of Branched Chain Keto-Acid Dehydrogenase Is a Potential Mechanism Coupling Branched-Chain Keto-Acid–Mediated-Astrocyte Activation to Branched-Chain Amino Acid Depletion-Mediated Cognitive Deficit after Traumatic Brain Injury

The effects of intra external iliac arterial infusions of leucine (114 μmol h−1 kg0.75) and insulin (0.34 U h−1 kg0.75) into the hindlimb on net whole blood branched-chain amino acid (BCAA), plasma branched-chain α-keto acid (BCKA) and glucose exchange across the hindlimb (HL) and portal-drained viscera (PDV) were investigated in chronically catheterized cattle. Leucine infusions increased (P < 0.05) arterial leucine and α-ketoisocaproate concentrations but did not affect the concentrations of other BCAA, BCKA or glucose. Leucine infusions resulted in a 4-fold increase (P < 0.1) in the net HL removal of leucine and a small increase (P < 0.1) in the net HL release of α-ketoisocaproate. Net whole blood BCAA, plasma BCKA and plasma glucose exchange across the PDV were unaffected by leucine infusions. Insulin infusions decreased (P < 0.1) whole blood leucine, plasma α-ketoisocaproate and plasma glucose concentrations and increased (P < 0.1) the HL extraction of plasma glucose. The HL and PDV extraction of whole blood BCAA and plasma BCKA were unaffected by insulin infusions. The data suggest that cattle are less sensitive to the effects of leucine and insulin on tissue BCAA catabolism compared to nonruminant species. Key words: Branched-chain amino acid, branched-chain α-keto acid, leucine, insulin, cattle

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

Canadian Journal of Animal Science ◽

10.4141/cjas87-106 ◽

1987 ◽

Vol 67 (4) ◽

pp. 1011-1020 ◽

Cited By ~ 3

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

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Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity

Experimental Hematology ◽

10.1016/j.exphem.2018.04.004 ◽

2018 ◽

Vol 63 ◽

pp. 12-16.e1 ◽

Cited By ~ 11

Author(s):

Adam C. Wilkinson ◽

Maiko Morita ◽

Hiromitsu Nakauchi ◽

Satoshi Yamazaki

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Amino Acid ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Hematopoietic Stem ◽

Branched Chain Amino Acid ◽

Amino Acid Imbalance ◽

Amino Acid Depletion ◽

Branched Chain

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.4.e475 ◽

1988 ◽

Vol 255 (4) ◽

pp. E475-E481 ◽

Cited By ~ 1

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)

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Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.3.e396 ◽

1987 ◽

Vol 252 (3) ◽

pp. E396-E407 ◽

Cited By ~ 2

Author(s):

K. P. Block ◽

W. B. Richmond ◽

W. B. Mehard ◽

M. G. Buse

Keyword(s):

Skeletal Muscle ◽

Amino Acid ◽

Active Enzyme ◽

Acid Oxidation ◽

Enzyme Complex ◽

Keto Acid ◽

Amino Acid Oxidation ◽

Acid Dehydrogenase ◽

Branched Chain Amino Acid ◽

Branched Chain

Muscle branched-chain alpha-keto acid dehydrogenase, the rate-limiting enzyme for branched-chain amino acid oxidation in skeletal muscle, was measured after treatment of rats with glucocorticoids. Cortisone treatment (10 mg X 100 g body wt-1 X day-1 for 2–5 days) resulted in an approximate doubling of the percentage of active enzyme. To further characterize this effect, the enzyme complex was measured 4 h after the intraperitoneal injection of 6 alpha-methylprednisolone, a water-soluble glucocorticoid with rapid onset effects. The percentage of active enzyme increased linearly as the dose of methylprednisolone was increased from 0.125 to 12.5 mg/100 g body wt, while total enzyme activity was unchanged. Administration of insulin with glucose had no significant effect on the activity of the enzyme. However, treatment of rats with insulin and glucose after methylprednisolone administration partially blocked branched-chain alpha-keto acid dehydrogenase activation. The activity of the enzyme complex was correlated with the concentration of leucine in plasma and muscle. Activation of skeletal muscle branched-chain alpha-keto acid dehydrogenase by increased glucocorticoids may play a role in the acceleration of branched-chain amino acid oxidation observed during severe stress.

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