SCIENTIFIC CONTRIBUTION & ACHIEVEMENTS

Research career spanning over the past 5 decades has contributed significantly to the contemporary progress in the area of biological oxidations. Some of his recent findings include the following :
 
 

RECENT FINDINGS

1. New functions of coenzyme Q: Water-soluble derivative of the lipid-quinone, coenzyme Q with side chain truncated by oxidation promoted relaxation of contracted arterial smooth muscle, much like nitric oxide. This opens potential of soluble forms of Q for alternate function besides well-known electron transport in mitochondria.

2. Cellular thermogenesis: An scheme involving activation of alpha-adrenergic receptor, generation of hydrogen peroxide, release of iron from stores and activation of NADPH-consuming lipid peroxidation is proposed as a heat-producing mechanism. By not involving any effect on ATP synthesis it has advantage over the mechanism dependent on uncoupling protein and proton discharge in mitochondria.

3. Hydrogen peroxide in cellular functions: Regulation of cellular metabolism by oxidative modifications by hydrogen peroxide had been supported by finding of rapid inactivation of several enzymes such as HMG-CoA reductase, glucose oxidase and glyceraldehydes3-phosphate dehydrogenase. Hydrogen peroxide, occurring in small concentrations, seems to act in presence of abundant cellular peroxicidal enzymes such as catalase, by forming a diperoxo-complex with vanadium that is stable to catalase, yet substitutes efficiently in peroxidations.

4. A new oxo-vanadium radical: A cycle of peroxo-vanadium compounds is constructed to explain oxygen consumption and oxidation of a variety of compounds such a NADH, bromide and benzoate. A radical, ú2), was identified as one of the intermediates formed by ESR spectrum that resembles that of hydroxyl radical but not modified by ethanol.

5. Polypeptide backbone in enzyme reactivity: The peptide bond between XG in the Walker loop in F1-ATPase (GXXXXGKT) flips on nucleotide binding and thus seems produces strain on the g-phosphate bond leading to its hydrolysis. This introduced the new concept that the polypeptide backbone has role in enzyme reactivity.

6. Transmembrane domains: Functional roles for transmembrane domains have been recognized in addition to anchoring the protein in the membrane. These short stretches of about 20 residues are conserved only for the hydrophobicity, but not sequence- selective, and have random choice of exon distribution; several domains in one exon, more than one exon for one domain and two exons sharing the triplet of a residue. Their characteristic codon sequence had been identified as having a pyrimidine inas the second letter, (X C/T X)n, which makes prediction of the domains possible from DNA sequence.

Prof.T.Ramasarma