Branched-chain amino acid oxidation by isolated rat tissue preparations

Shinnick, Fred L.; Harper, Alfred E.

doi:10.1016/0304-4165(76)90016-7

“…31 In the present study, basal (actual) the largest capacity to transaminate BCAAs, but BCKDH activity and activity state are very low in this tissue. 14,19,20 liver BCKDH activity was significantly lower in livers from patients with cirrhosis. Thus, our data suggest that BCAA Thus, in this model peripheral transamination in skeletal muscle results in significant release of branched-chain a-keto oxidation in liver would be lower in alcoholics with cirrhosis.…”

Section: Discussionmentioning

confidence: 90%

The Valine Catabolic Pathway in Human Liver: Effect of Cirrhosis on Enzyme Activities

Taniguchi

¹

,

Nonami

²

,

Nakao

³

et al. 1996

View full text Add to dashboard Cite

its tissue specificity have been studied intensively in rats. 2 The activities of key enzymes in the valine cataThe first step in BCAA catabolism, which takes place largely bolic pathway -branched-chain aminotransferase, in extrahepatic tissues, is reversible transamination of the branched-chain a-keto acid dehydrogenase complex, BCAAs to produce the branched-chain a-keto acids catalyzed methacrylyl (MC)-coenzyme A (CoA) hydratase (croby the branched-chain aminotransferase (BCAT). The second tonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hystep, which occurs largely in the liver, is irreversible oxidadrolase -were measured in normal and cirrhotic hutive decarboxylation of the a-keto acids to produce their coenman livers. Unlike rat liver, which does not contain zyme A (CoA) esters catalyzed by the branched-chain a-keto branched-chain aminotransferase, the aminotransacid dehydrogenase (BCKDH) complex (Fig. 1). The latter is ferase activity in the normal liver was measurable the committed step in the BCAA catabolism. After dehydrogeand is increased somewhat in cirrhosis of the human nation of CoA esters, each compound is metabolized individuliver. The total activity of branched-chain a-keto acid ally by a separate pathway. dehydrogenase complex in the normal human liver Among these pathways, valine catabolism is unique bewas Ç1% of that in rat liver, and 20% to 30% of the cause methacrylyl-CoA (MC-CoA), a potentially toxic comcomplex was in the active form in both normal and pound, is formed in the middle part of the pathway and is cirrhotic livers. Only the actual activity of the endetoxified in two steps by MC-CoA hydratase (crotonase) and zyme was significantly decreased by cirrhosis. These 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase ( Fig. 1). MCresults suggest that human liver is less active thanCoA is a toxic compound because of its strong tendency to rat liver in the catabolism of branched-chain amino react with free thiol groups of proteins and glutathione. 4,5 and a-keto acids. Activities of MC-CoA hydratase andThat it is toxic in vivo is supported by clinical findings in HIB-CoA hydrolase in human liver were very high an infant with an almost complete deficiency in HIB-CoA compared with that of branched-chain a-keto acid hydrolase. 5 This child had multiple congenital physical maldehydrogenase complex, suggesting an important formations, excreted large quantities of cysteine/cysteamine role for these enzymes in catabolism of a potentially conjugates of methacrylate, and died of a cardiac lesion at 3 toxic compound, MC-CoA, formed as an intermediate months. in the catabolism of valine and isobutyrate. CirrhosisFormation of a monocarboxylic acid, ((S)-3-hydroxyisoburesulted in a significant decrease in HIB-CoA hytyric acid), which readily diffuses out of cells after being drolase activity but had no effect on the citrate formed by HIB-CoA hydrolase, is suggested to be physiologisynthase activity, suggesting that the decrease in cally important for protection of cells against the toxic effects HIB-CoA hydro...

show abstract

“…28,29 There are dramatic alterations in the structure of liver in liver, hence oxidative capacity is concentrated in the liver. 14 Neither BCAT isozyme is found in rat liver, 17,18 and mitochondria in alcoholic humans. 30 The same alterations are seen in animal models for alcoholism and are accompanied the low levels of detectable activity probably represent other aminotransferase activities.…”

Section: Discussionmentioning

confidence: 97%

“…For example, valine produced by proteolysis of undi-BCAA catabolism is achieved in large part by the distribution and activities of the first two enzymes in the catabolic path-gested protein in the colon is converted by bacterial fermentation into isobutyric acid, which is then transported to the way, the BCAT and BCKDH complex. 1,[14][15][16] In the rat BCKDH complex, both actual (active) and total activities are highest liver by the portal blood. 28,29 There are dramatic alterations in the structure of liver in liver, hence oxidative capacity is concentrated in the liver.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The valine catabolic pathway in human liver: Effect of cirrhosis on enzyme activities

Taniguchi

1996

Hepatology

3

0

View full text Add to dashboard Cite

its tissue specificity have been studied intensively in rats. 2 The activities of key enzymes in the valine cataThe first step in BCAA catabolism, which takes place largely bolic pathway -branched-chain aminotransferase, in extrahepatic tissues, is reversible transamination of the branched-chain a-keto acid dehydrogenase complex, BCAAs to produce the branched-chain a-keto acids catalyzed methacrylyl (MC)-coenzyme A (CoA) hydratase (croby the branched-chain aminotransferase (BCAT). The second tonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hystep, which occurs largely in the liver, is irreversible oxidadrolase -were measured in normal and cirrhotic hutive decarboxylation of the a-keto acids to produce their coenman livers. Unlike rat liver, which does not contain zyme A (CoA) esters catalyzed by the branched-chain a-keto branched-chain aminotransferase, the aminotransacid dehydrogenase (BCKDH) complex (Fig. 1). The latter is ferase activity in the normal liver was measurable the committed step in the BCAA catabolism. After dehydrogeand is increased somewhat in cirrhosis of the human nation of CoA esters, each compound is metabolized individuliver. The total activity of branched-chain a-keto acid ally by a separate pathway. dehydrogenase complex in the normal human liver Among these pathways, valine catabolism is unique bewas Ç1% of that in rat liver, and 20% to 30% of the cause methacrylyl-CoA (MC-CoA), a potentially toxic comcomplex was in the active form in both normal and pound, is formed in the middle part of the pathway and is cirrhotic livers. Only the actual activity of the endetoxified in two steps by MC-CoA hydratase (crotonase) and zyme was significantly decreased by cirrhosis. These 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase ( Fig. 1). MCresults suggest that human liver is less active thanCoA is a toxic compound because of its strong tendency to rat liver in the catabolism of branched-chain amino react with free thiol groups of proteins and glutathione. 4,5 and a-keto acids. Activities of MC-CoA hydratase andThat it is toxic in vivo is supported by clinical findings in HIB-CoA hydrolase in human liver were very high an infant with an almost complete deficiency in HIB-CoA compared with that of branched-chain a-keto acid hydrolase. 5 This child had multiple congenital physical maldehydrogenase complex, suggesting an important formations, excreted large quantities of cysteine/cysteamine role for these enzymes in catabolism of a potentially conjugates of methacrylate, and died of a cardiac lesion at 3 toxic compound, MC-CoA, formed as an intermediate months. in the catabolism of valine and isobutyrate. CirrhosisFormation of a monocarboxylic acid, ((S)-3-hydroxyisoburesulted in a significant decrease in HIB-CoA hytyric acid), which readily diffuses out of cells after being drolase activity but had no effect on the citrate formed by HIB-CoA hydrolase, is suggested to be physiologisynthase activity, suggesting that the decrease in cally important for protection of cells against the toxic effects HIB-CoA hydro...

show abstract

“…The second enzyme is an irreversible branched-chain 2-oxo acid dehydrogenase (EC 1.2.4.4). It has been suggested that branchedchain amino acid metabolism proceeds only as far as the 2-oxo acid in muscle, and that these 2-oxo acids leave muscle and are further metabolized in liver (Wohlhueter & Harper, 1970;Shinnick & Harper, 1976;Odessey & Goldberg, 1979). This idea was originally based on the fact that, in muscle, the activity of the branched-chain amino acid aminotransferase is high relative to that of the branched-chain 2-oxo acid dehydrogenase.…”

Section: Introductionmentioning

confidence: 99%

Valine metabolism Gluconeogenesis from 3-hydroxyisobutyrate

Letto¹,

Brosnan²,

Brosnan³

1986

Biochemical Journal

View full text Add to dashboard Cite

During valine catabolism in muscle both 2-oxoisovalerate and 3-hydroxyisobutyrate can be released into the circulation. 3-Hydroxyisobutyrate is a good gluconeogenic substrate in isolated cortical tubules and hepatocytes. The maximal rate of gluconeogenesis from 3-hydroxyisobutyrate was greater than from 2-oxoisovalerate. We propose that 3-hydroxyisobutyrate is an inter-organ metabolite by which the gluconeogenic potential of valine, whose catabolism has been initiated in muscle, may be conserved.

show abstract

Branched-chain amino acid oxidation by isolated rat tissue preparations

Cited by 212 publications

References 19 publications

The Valine Catabolic Pathway in Human Liver: Effect of Cirrhosis on Enzyme Activities

The Valine Catabolic Pathway in Human Liver: Effect of Cirrhosis on Enzyme Activities

The valine catabolic pathway in human liver: Effect of cirrhosis on enzyme activities

Valine metabolism Gluconeogenesis from 3-hydroxyisobutyrate

Contact Info

Product

Resources

About