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K P Block

Publications and source records attributed to K P Block.

27 records · Page 2Linked to original sources
PubMed1987

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

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.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1987

Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis.

Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH4Cl X 100 g body wt-1 X day-1. Epitrochlearis muscles were incubated with L-[1-14C]-valine and L-[1-14C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower (P less than 0.05) in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher (P less than 0.05) in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain alpha-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. We conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain alpha-keto acid dehydrogenase.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1987

Modulation of rat skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo. Effects of dietary protein and meal consumption.

The effects of dietary protein on the activity of skeletal muscle branched-chain alpha-keto acid dehydrogenase (BCKAD) were investigated. BCKAD is rate-limiting for branched-chain amino acid (BCAA) catabolism by muscle; its activity is modulated by phosphorylation-dephosphorylation. In rats fed an adequate protein (25% casein) diet, BCKAD was approximately 2% active postabsorptively and increased to 10% or 16% active after a 25% or 50% protein meal, respectively. Prolonged feeding of a 50% protein diet increased postabsorptive BCKAD activity to 7% with further increases to 40% active postprandially. On a low protein (9% casein) diet BCKAD remained approximately 2% active regardless of meal-feeding. Dose-dependent activation of BCKAD by intravenous leucine in postabsorptive rats was blunted by a low protein diet. We conclude that excesses of dietary protein enhance the capacity of skeletal muscle to oxidize BCAA, muscle conserves BCAA when protein intake is inadequate, and skeletal muscle may play an important role in whole-body BCAA homeostasis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1986

Leucine and isoleucine activate skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo.

The response of rat skeletal muscle branched-chain alpha-keto acid dehydrogenase to administration of branched-chain amino acids in vivo was determined using a soluble preparation of the enzyme. After detergent extraction of the complex in the presence of kinase and phosphatase inhibitors, initial in vivo activity was typically 1 nmol X min-1 X g muscle-1, with 0.1 mM alpha-[1-14C]ketoisocaproate as substrate. Total activity of the dephosphorylated complex, measured after preincubation with 15 mM Mg2+, typically reached a maximum of 29 nmol X min-1 X g-1. Thus in overnight-fasted rats the complex was 2-3% active. Initial activity increased three- to fivefold after leucine or isoleucine (at higher concentrations) but not valine administration in vivo. After intravenous leucine injection (0.25 mmol/kg) initial muscle enzyme activity increased rapidly and subsequently decreased, paralleling plasma leucine concentrations, while plasma valine and isoleucine decreased. In conclusion, muscle branched-chain alpha-keto acid dehydrogenase complex is rapidly activated when circulating leucine is increased to concentrations that may occur after meals. During hyperleucinemia accelerated valine and isoleucine degradation by muscle may account for the observed "antagonism" among the branched-chain amino acids.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1985

Activation of rat liver branched-chain 2-oxo acid dehydrogenase in vivo by glucagon and adrenaline.

The activity of liver branched-chain 2-oxo acid dehydrogenase complex was measured in rats fed on low-protein diets and given adrenaline, glucagon, insulin or dibutyryl cyclic AMP in vivo. Administration of glucagon or adrenaline (200 micrograms/100 g body wt.) resulted in a 4-fold increase in the percentage of active complex. As with glucagon and adrenaline, treatment of rats with cyclic AMP (5 mg/100 g body wt.) resulted in marked activation of branched-chain 2-oxo acid dehydrogenase. Insulin administration (1 unit/100 g body wt.) also resulted in activation of enzyme; however, these effects were less than those observed with glucagon and adrenaline. In contrast with the results obtained with low-protein-fed rats, administration of adrenaline (200 micrograms/100 g body wt.) to rats fed with an adequate amount of protein resulted in only a modest (14%) increase in the activity of the complex. The extent to which these hormones activate branched-chain 2-oxo acid dehydrogenase appears to be correlated with their ability to stimulate amino acid uptake into liver.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1985

Activation of liver branched-chain alpha-keto acid dehydrogenase in rats by excesses of dietary amino acids.

As part of an effort to explain the leucine-induced depressions of plasma isoleucine and valine concentrations, and the concomitant stimulation of valine oxidation in vivo, branched-chain alpha-keto acid dehydrogenase (BCKAD) activity was measured in livers from rats that were fed for only 6 h/d large quantities of individual amino acids in a low protein diet. Preincubation of homogenates with buffer containing Mg2+ and Ca2+ allowed estimation of fully active complex. Cytosolic and mitochondrial branched-chain-amino-acid aminotransferase (BCAAT) activities were also measured in livers of rats fed an excess of leucine. The percentage of BCKAD in the active form in livers of rats fed the low protein diet containing an excess of leucine, isoleucine, valine or phenylalanine for 2 d was double that of rats fed the low protein control diet (control, leucine, isoleucine, valine and phenylalanine groups having, respectively, 45 +/- 2, 85 +/- 7, 85 +/- 3, 95 +/- 5, and 81 +/- 4% of hepatic BCKAD in the active form). Consumption of a low protein diet containing an excess of leucine had no significant effect on either cytosolic or mitochondrial BCAAT activities of liver. The response of BCKAD in liver can contribute to the leucine-induced stimulation of valine oxidation in vivo but analysis of the results of this study leads to the conclusion that other mechanisms, probably in nonhepatic tissues, must also be involved.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1984

Valine metabolism in vivo: effects of high dietary levels of leucine and isoleucine.

The short-term effects of feeding rats high levels of L-leucine or L-isoleucine on valine metabolism in vivo have been investigated. Consumption of a low-protein diet containing an additional 5% of leucine resulted in depression within one hour of the plasma concentrations of isoleucine, valine, alpha-keto-beta-methylvalerate, and alpha-ketoisovalerate. Concurrently with these changes in blood branched-chain amino acids and branched-chain ketoacids was a rapid increase (51%) in whole-body L-[1-14C]-valine oxidation. Studies with intragastrically administered leucine solutions indicated that the depressions in blood concentrations of valine occurred over the same time period as the stimulation in valine oxidation. In contrast, consumption of a low-protein diet containing an additional 5% of isoleucine had no significant effect on the plasma concentrations of leucine, valine, and alpha-ketoisocaproate; a significant (P less than 0.01) depression in the plasma concentration of alpha-ketoisovalerate was observed three hours after the diet containing excess isoleucine had been consumed. In contrast to the results obtained with excess leucine, consumption of excess isoleucine had no significant effect on the rate of valine oxidation in vivo. As part of an effort to explain the leucine-induced depletion of plasma valine and stimulation of valine oxidation, liver and muscle branched-chain aminotransferase and liver branched-chain ketoacid dehydrogenase activities were measured. Consumption of excess leucine had no significant effect on either muscle or liver aminotransferase activities, but was associated with a greater than two-fold increase in hepatic dehydrogenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Branched-Chain↗