As a step towards understanding the structure and function of phospholipases A2 (PLA2s), five cDNAs encoding Trimeresurus flavoviridis venom gland PLA2 isozymes have been sequenced. They revealed that the 5' and 3' untranslated regions are much more homologous than the protein-coding regions and that base substitutions have occurred at similar rates for the three positions of codons in the protein-coding regions. Such novel findings are of great interest from the viewpoint of molecular evolution. To gain a further insight into this evolutional phenomenon, we have isolated and sequenced six T. flavoviridis PLA2 isozyme genes. Each gene consisted of four exons and three introns and encoded protein of 138 amino-acid residues, including the signal sequence of 16 amino-acid residues. The introns were much more homologous than the protein-coding regions of exons except for the signal peptide-coding region of the first exon. The absence of apparent functional role in the introns suggested that the protein-coding regions, except for the signal peptide-coding domains, have evolved at greater substitution rates than introns. The fact that the numbers of nucleotide substitutions per non-synonymous site are close to or larger than the numbers of nucleotide substitutions per synonymous site for relevant pairs of genes revealed that Darwinian-type accelerated substitutions have occurred in the protein-coding regions of exons. This is compatible with the presence of PLA2 species with diverse physiological activities in the venom.

Amino Acid Sequence↗

PubMedDate not supplied

Accelerated conversion of dehydroepiandrosterone sulfate to estrogen in a patient with Crow-Fukase syndrome and diabetes mellitus.

About 28% of patients with the Crow-Fukase syndrome exhibit glucose intolerance which may be induced by low serum levels of dehydroepiandrosterone (DHEA). We report a patient with the Crow-Fukase syndrome who exhibited non-insulin dependent diabetes mellitus (NIDDM) worsened prior to admission. He received the DHEA sulfate (DHEA-S) infusion test to evaluate aromatase activity. This patient exhibited an increase in aromatase activity measured by the conversion of the intravenously loaded DHEA-S to estrogen, and low serum levels of DHEA and DHEA-S. These abnormalities returned to nearly normal during the administration of prednisolone, 60 mg per day. No adverse effect on his diabetes was observed during the corticosteroid treatment. Five control patients with diabetes but without the Crow-Fukase syndrome showed no increase in the conversion of DHEA-S to estrogen, which suggests that aromatase activity is normal in diabetes. The increase in aromatase activity in our patient may have led to a low serum concentration of DHEA that in turn caused glucose intolerance and a deterioration of the diabetes prior to admission. Glucocorticoid therapy may be beneficial in Crow-Fukase syndrome to improve the distorted metabolism of DHEA with no adverse effect on the diabetes.

Aromatase↗