Transaminase of branched chain amino acids II. Physiological change in enzyme activity in rat liver and kidney

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.

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Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase

Biochemical Journal ◽

10.1042/bj2040487 ◽

1982 ◽

Vol 204 (2) ◽

pp. 487-492 ◽

Cited By ~ 5

Author(s):

E E May ◽

M E May ◽

R P Aftring ◽

M G Buse

Keyword(s):

Amino Acids ◽

Rat Liver ◽

Maternal Diabetes ◽

Perinatal Period ◽

Branched Chain Amino Acids ◽

Developmental Changes ◽

Acid Dehydrogenase ◽

Period 2 ◽

Liver Homogenates ◽

Branched Chain

Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weaning. The apparent Vmax, of the enzyme increased with age, but its Km appeared unchanged. The data suggest that hepatic branched-chain 2-oxo acid dehydrogenase is induced or activated during the perinatal period. The enzyme's activity at birth was unaffected by maternal diabetes, or by treating the mother with pharmacological doses of corticosterone or 3,3',5-tri-iodothyronine, during the last 5 days of pregnancy.

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Developmental Changes of Glutamate Dehydrogenase Activity in Rat Liver Mitochondria and Its Enhancement by Branched-Chain Amino Acids

Neonatology ◽

10.1159/000243858 ◽

1992 ◽

Vol 62 (2-3) ◽

pp. 83-88 ◽

Cited By ~ 3

Author(s):

Katsuto Eguchi ◽

Masaru Yonezawa ◽

Yukiteru Mitsui ◽

Yuji Hiramatsu

Keyword(s):

Amino Acids ◽

Glutamate Dehydrogenase ◽

Dehydrogenase Activity ◽

Rat Liver ◽

Liver Mitochondria ◽

Branched Chain Amino Acids ◽

Developmental Changes ◽

Rat Liver Mitochondria ◽

Glutamate Dehydrogenase Activity ◽

Branched Chain

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Effect of branched-chain amino acids on proteolytic enzymes gene expression in rat liver

Clinical Nutrition ◽

10.1016/0261-5614(93)90257-5 ◽

1993 ◽

Vol 12 ◽

pp. 36

Author(s):

A.L. Andreu ◽

S. Schwartz ◽

J. López ◽

M.A. Arbós ◽

M. Quiles ◽

...

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Rat Liver ◽

Proteolytic Enzymes ◽

Branched Chain Amino Acids ◽

Branched Chain

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Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver

Hepatology Research ◽

10.1016/j.hepres.2005.07.001 ◽

2005 ◽

Vol 33 (1) ◽

pp. 27-32 ◽

Cited By ~ 36

Author(s):

T MATSUMURA ◽

Y MORINAGA ◽

S FUJITANI ◽

K TAKEHANA ◽

S NISHITANI ◽

...

Keyword(s):

Amino Acids ◽

Oral Administration ◽

Rat Liver ◽

Branched Chain Amino Acids ◽

Branched Chain

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Cell swelling inhibits proteolysis in perfused rat liver

Biochemical Journal ◽

10.1042/bj2720239 ◽

1990 ◽

Vol 272 (1) ◽

pp. 239-242 ◽

Cited By ~ 67

Author(s):

D Häussinger ◽

C Hallbrucker ◽

S vom Dahl ◽

F Lang ◽

W Gerok

Keyword(s):

Amino Acids ◽

Rat Liver ◽

Liver Cell ◽

Intraperitoneal Injection ◽

Branched Chain Amino Acids ◽

Cell Swelling ◽

Perfused Rat Liver ◽

Close Relationship ◽

Branched Chain

Exposure of isolated single-pass-perfused rat liver to hypo-osmotic media resulted in liver cell swelling and an inhibition of release of branched-chain amino acids. Similarly, cell swelling inhibited [3H]leucine release from perfused livers from rats in which liver proteins were prelabelled in vivo by intraperitoneal injection of L-[4,5-3H]leucine 16-20 h before the experiment. The effects of cell swelling on [3H]leucine release were fully reversible. [3H]Leucine release was also inhibited when cell swelling was induced by addition of glutamine (0.5-2 mM). There was a close relationship between the inhibition of [3H]leucine release and the degree of liver cell swelling, regardless of whether cell swelling was induced by hypo-osmotic perfusion or addition of glutamine. The data suggest that the known anti-proteolytic effect of glutamine is in large part due to glutamine-induced hepatocyte swelling.

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Two Forms of Herbicide-Sensitive Acetolactate Synthase under Different Control by 2-Oxobutyrate in Rhodospivillum rubrum

Zeitschrift für Naturforschung C ◽

10.1515/znc-1990-9-1011 ◽

1990 ◽

Vol 45 (9-10) ◽

pp. 999-1003

Author(s):

Jobst-Heinrich Klemme ◽

Irmgard Schneider

Keyword(s):

Amino Acids ◽

Enzyme Activity ◽

Rhodospirillum Rubrum ◽

Culture Media ◽

Acetolactate Synthase ◽

Branched Chain Amino Acids ◽

Standard Test ◽

Lag Phase ◽

Test Mixture ◽

Branched Chain

Regulation of acetolactate synthase (ALS, EC 4.1.3.18) in the phototrophic prokaryote Rhodospirillum rubrum was studied. In cell free extracts of 5 strains investigated, enzyme activity was very labile (about 80% loss of activity within 12h during storage at 4 °C) but was stabilized to some extent by 10 (μM FAD and 20 vol.% glycerol. By filtration of extracts through Superose 6 HR gels (FPLC technique), ALS activity of all strains was separated in two fractions of 200 and 600 kDa, respectively. The enzyme fractions had about the same affinity to pyruvate (ATm = 1.6 - 1.8 m M) , the same sensitivity to L-valine (50 and 65% inhibition by 0.1 m M valine in the standard test mixture) and the herbicide sulfometuron methyl (90 and 92% inhibition by 1 μM herbicide), but differed greatly in their sensitivity to inhibition by 0.4 m NaCl. In culture media with 2-oxobutyrate (2-OB), growth began only after a lag-phase of several days (5 days with 1 mM of the inhibitor). Cells grown in the presence of 2-OB had a reduced total ALS activity and did not contain the 200 kDa fraction. The inhibition of ALS by valine was noncompetitive in respect to pyruvate (K1= 0.l m M ) . From other branched-chain amino acids tested (L-leucine, L-isoleucine, norvaline, norleucine) only isoleucine was inhibitory (K1; = 3.1 m M )

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The adaptation in musle oxidation of leucine to dietary protein and energy intake

British Journal Of Nutrition ◽

10.1079/bjn19740041 ◽

1974 ◽

Vol 31 (3) ◽

pp. 333-342 ◽

Cited By ~ 38

Author(s):

R. D. Sketcher ◽

E. B. Fern ◽

W. P. T. James

Keyword(s):

Amino Acids ◽

Enzyme Activity ◽

Dehydrogenase Activity ◽

Liver Enzyme ◽

Branched Chain Amino Acids ◽

Metabolizable Energy ◽

Muscle Enzyme ◽

Oxidation Activity ◽

Branched Chain

1. Female hooded rats (65g) were maintained on a high-protein (HP) or low-protein (LP) diet for 2 weeks (ratio, energy supplied by utilizable protein: total metabolizable energy 10 and 3.5 respectively) and the oxidation of both L- and DL-[1-14C]leucine in vivo was measured in the fed and fasted animal.2. Oxidation of leucine in vivo was reduced in the animals given the LP diet. Fasting caused an increase in the oxidation of the branched-chain amino acids.3. Leucine-α-oxoglutarate transaminase (EC 2.6.1.6) and α-ketoisocaproic acid dehydrogenase were measured in both liver and gastrocnemius muscle from rats fed on the HP or LP diet. Enzymes were also assayed after a 48 h fast in a group of animals previously maintained on the HP diet.4. The LP diet led to a fall in muscle dehydrogenase activity without any alterations in liver enzyme activity. Fasting also reduced muscle dehydrogenase activity but increased liver dehydrogenase activity.5. The presence of a dehydrogenase in muscle and its ability to adapt to dietary stress at a time when the liver enzyme is unaffected suggests that muscle is the most important site for control of leucine oxidation.6. Transaminase activity in muscle rose in the LP and fasted animals but the activity in liver was unchanged.7. Oxidation, incorporation into protein of [U-14C]leucine and the pool sizes of free leucine in plasma and in the extensor digitorum longus muscles were measured. The rats were maintained under the feeding conditions described above. The ability of incubated muscles to incorporate [14C]leucine into protein in both the fasted animals and those fed on the LP diet was reduced. Oxidation of leucine in muscle was reduced in protein deficiency but there was little change in the evolution of 14CO2 from [U-14C]leucine on fasting.8. The increase in pool size of free leucine in fasted animals is probably important in determining its rate of oxidation in muscle, as 14CO2 production was maintained despite falling activities of the dehydrogenase enzyme activity. The muscle enzyme accounted for 90% of the calculated body capacity for oxidation; activity in liver is insufficient to deal with normal rates of oxidation. Muscle enzyme is normally in excess of that required for the oxidation of branched-chain amino acids.

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