• S S Wagh

      Articles written in Journal of Biosciences

    • Lipoic acid and diabetes II: Mode of action of lipoic acid

      V M Gandhi S S Wagh C V Natraj K K G Menon

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      Intraperitoneal administration of lipoic acid (10 mg/100 g) does not effect changes in serum insulin levels in normal and alloxan diabetic rats, while normalising increased serum pyruvate, and impaired liver pyruvic dehydrogenase characteristic of the diabetic state. Dihydrolipoic acid has been shown to participate in activation of fatty acids with equal facility as coenzyme A. Fatty acyl dihydrolipoic acid however is sparsely thiolyzed to yield acetyl dihydrolipoic acid. Also acetyl dihydrolipoic acid does not activate pyruvate carboxylase unlike acetyl coenzyme A. The reduced thiolysis of Β-keto fatty acyl dihydrolipoic acid esters and the lack of activation of pyruvic carboxylase by acetyl dihydrolipoic acid could account for the antiketotic and antigluconeogenic effects of lipoic acid

    • Lipoic acid and diabetes—Part III: Metabolic role of acetyl dihydrolipoic acid

      S S Wagh V M Gandhi C V Natraj K K G Menon

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      Rat liver lipoyl transacetylase catalyzes the formation of acetyl dihydrolipoic acid from acetyl coenzyme A and dihydrolipoic acid. In an earlier paper the formation of acetyl dihydrolipoic from pyruvate and dihydrolipoic acid catalyzed by pyruvate dehydrogenase has been reported. Acetyl dihydrolipoic acid is a substrate for citrate synthase, acetyl coenzyme A carboxylase and fatty acid synthetase. The Vmax. for citrate synthase with acetyl dihydrolipoic acid was identical to acetyl coenzyme A (approximately 1 μmol citrate formed/min/mg protein) while the apparent Km was approximately 4 times higher with acetyl dihydrolipoic acid as the substrate. This may be due to the fact that synthetic acetyl dihydrolipoic acid is a mixture of 4 possible isomers and only one of them may be the substrate for the enzymatic reaction. While dihydrolipoic acid can replace coenzyme A in the activation of succinate catalyzed by succinyl coenzyme A synthetase, the transfer of coenzyme A between succinate and acetoacetyl dihydrolipoic acid catalyzed by succinyl coenzyme A: 3 oxo-acid coenzyme A transferase does not occur.

    • Mode of action of lipoic acid in diabetes

      S S Wagh C V Natraj K K G Menon

      More Details Abstract Fulltext PDF

      Metabolic aberrations in diabetes such as hyperglycemia, ketonemia, ketonuria, reduced glycogen in tissues and reduced rates of fatty acid synthesis in the liver are corrected by the administration of lipoic acid. Dithiol octanoic acid is formed from lipoic acid by reduction and substitutes for Coenzyme A in several enzymatic reactions such as pyruvate dehydrogenase, citrate synthase, acetyl Coenzyme A carboxylase, fatty acid synthetase, and triglyceride and phospholipid biosynthesis; but not in the oxidation of fatty acids because of the slow rates of thiolysis of β-keto acyl dithioloctanoic acid. The overall effect of these changes in the key enzymic activities is seen in the increased rates of oxidation of glucose and a reduction in fatty acid oxidation in diabetes following lipoic acid administration.

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