EurekaMag.com logo
+ Translate

Regulation of leucine catabolism mechanism responsible for oxidizable substrate inhibition and di chloro acetate stimulation of leucine oxidation by the heart


, : Regulation of leucine catabolism mechanism responsible for oxidizable substrate inhibition and di chloro acetate stimulation of leucine oxidation by the heart. Archives of Biochemistry & Biophysics 200(2): 336-345

In the absence of any other oxidizable substrate, the perfused rat heart oxidizes [1-14C]-leucine to 14CO2 at a rapid rate and releases only small amounts of .alpha.[1-14C]ketoisocaproate into the perfusion medium. The branched-chain .alpha.-keto acid dehydrogenase complex, assayed in extracts of mitochondria prepared from such perfused hearts, is very active. Under such perfusion conditions, dichloroacetate has almost no effect on [1-14C]leucine oxidation, .alpha.-[1-14C]ketoisocaproate release, or branched-chain .alpha.-keto acid dehydrogenase activity. Perfusion of the heart with some other oxidizable substrate, i.e., glcuose, pyruvate, ketone bodies, or palmitate, results in an inhibition of [1-14C]leucine oxidation to 14CO2 and the release of large amounts of .alpha.-[1-14C]ketoisocaproate into the perfusion medium. The branched-chain .alpha.-keto acid dehydrogenase complex, assayed in extracts of mitochondria prepared from such hearts, is almost completely inactivated. The enzyme can be reactivated by incubating the mitochondria at 30.degree. C without an oxidizable substrate. With hearts perfused with glucose or ketone bodies, dichloroacetate greatly increases [1-14C]leucine oxidation, decreases .alpha.-[1-14C]ketoisocaproate release into the perfusion medium, and activates the branched-chain .alpha.-keto acid dehydrogenase complex. Pyruvate may block dichloroacetate uptake because dichloroacetate neither stimulates [1-14C]leucine oxidation nor activates the branched-chain .alpha.-keto acid dehydrogenase complex of pyruvate-perfused hearts. Leucine oxidation by heart may be regulated by the activity of the branched-chain .alpha.-keto acid dehydrogenase complex which is subject to interconversion between active and inactive forms. Oxidizable substrates establish conditions which inactivate the enzyme. Dichloroacetate, known to activate the pyruvate dehydrogenase complex by inhibition of pyruvate dehydrogenase kinase, causes activation of the branched-chain .alpha.-keto acid dehydrogenase complex, suggesting the existence of a kinase for this complex.

(PDF 0-2 workdays service)

Accession: 006288987

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Sans, R.M.; Jolly, W.W.; Harris, R.A., 1980: Studies on the regulation of leucine catabolism. Mechanism responsible for oxidizable substrate inhibition and dichloroacetate stimulation of leucine oxidation by the heart. Archives of Biochemistry and Biophysics 200(2): 336-345

Harris, R.A.; Crabb, D.W.; Sans, R.M., 1978: Studies on the regulation of leucine catabolism part 2 mechanism responsible for di chloro acetate stimulation of leucine oxidation by the liver. Dichloroacetate, an activator of the pyruvate dehydrogenase (EC 1.2.4.1) complex and a hypoglycemic agent, activates leucine oxidation by isolated [rat] liver cells. The .alpha.-ketoisocaproate dehydrogenase complex, which catalyzes the 2nd step o...

Sans, R.M.; Jolly, W.W.; Harris, R.A., 1980: Regulation of leucine catabolism 3. effects of di chloro acetate and 2 chloro propionate on leucine oxidation by the heart. The effect of dichloroacetate, an activator of pyruvate dehydrogenase and a hypoglycemic agent, on the oxidation of leucine by the perfused rat heart was studied. Dichloroacetate promotes leucine oxidation in the liver with the mechanism involving...

Harris, R.A.; Crabb, D.W.; Sans, R.M., 1978: Studies on the regulation of leucine catabolism. II. Mechanism responsible for dichloroacetate stimulation of leucine oxidation by the liver. Archives of Biochemistry and Biophysics 190(1): 8-16

Harris R.A.; Crabb D.W.; Sans R.M., 1978: Mechanism responsible for di chloro acetate stimulation of leucine oxidation by isolated liver cells. Federation Proceedings 37(3): 594

Sans, R.M.; Jolly, W.W.; Harris, R.A., 1980: Studies on the regulation of leucine catabolism. III. Effects of dichloroacetate and 2-chloropropionate on leucine oxidation by the heart. Journal of Molecular and Cellular Cardiology 12(1): 1-16

Sans R.M., 1979: Effect of di chloro acetate on leucine catabolism by perfused heart. Federation Proceedings 38(3 PART 1): 829

Rogerson A.C.; Freundlich M., 1970: Control of iso leucine valine and leucine biosynthesis part 8 mechanism of growth inhibition by leucine in relaxed and stringent strains of escherichia coli k 12. Biochimica et Biophysica Acta 208(1): 87-98

Borgonha, S.; Oh, S.H.; Metges, C.; Bequette, B.; Young, V.R., 2002: 24H kinetics of leucine oxidation in subjects receiving either -leucine as free amino acid or as intrinsically labeled leucine-casein. We have proposed a new leucine requirement of 39 mg/kg/d for adults. Nitrogen intake in these studies was provided as an L-amino acid mixture. In an earlier experiment, conducted over an 8h fed period at 120 mg/kg/d of leucine intake, 13CO2-produc...

Crabb, D.W.; Harris, R.A., 1978: Studies on the regulation of leucine catabolism in the liver. Stimulation by pyruvate and dichloroacetate. The rate of oxidation of L-[1-14C]leucine to 14CO2 by isolated rat hepatocytes is increased by pyruvate and dichloroacetate. This effect is specific for L-leucine, not being observed for L-valine, L-isoleucine, or D-leucine. Transamination, the ra...