Effects of hypophysectomy and thyroidectomy on leucine metabolism in adipose tissue.
Hypophysectomy doubled the rate of oxidation of L-[1-14C]leucine to 14CO2 by segments of rat epididymal adipose tissue. Thyroidectomy, but not adrenalectomy, produced identical results. Acceleration of leucine oxidation occurred even in the presence of glucose and saturating concentrations of insulin and leucine, suggesting that thyroidectomy increased the capacity to degrade leucine. Treatment of thyroidectomized rats with triiodothyronine (T3) decreased leucine oxidation, but at least 4 days were required. Treatment of hypophysectomized rats with T3 for 6 days was ineffective unless growth hormone was also given. A similar acceleration was also seen in the rate of oxidation of alpha-keto[1-14C]isocaproate, the deaminated analogue of leucine, but neither hypophysectomy nor thyroidectomy accelerated the rate of oxidation of isovalerate, the next metabolite in the degradative sequence. These observations suggested that hypothyroidism, whether primary or secondary, might increase the activity of the mitochondrial reaction responsible for the decarboxylation of alpha-ketoisocaproate. Because thyroidectomy failed to modify the rate of oxidation of [1-14C]pyruvate that occurs by an analogue reaction and requires the same cofactors, an effect of thyroidectomy on cofactor availability was ruled out. Direct assay in a cell-free homogenate revealed a nearly twofold increase in the activity of the alpha-ketoisocaproate dehydrogenase enzyme complex. The findings support the conclusion that hypothyroidism increases the amount or activity of the mitochondrial enzyme complex responsible for decarboxylation of branched-chain alpha-keto acids.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D002208:Caproates / Q000378:metabolism; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D007651:Keto Acids / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D008297:Male; D051381:Rats; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology
D002208:Caproates; D007328:Insulin; D007651:Keto Acids; D014284:Triiodothyronine; C013082:alpha-ketoisocaproic acid; D007930:Leucine