Martin J. Sweeney

BIOCHEMISTRY AND BIOLOGICAL EFFECTS OF THE PYRAZOFURINS* (PYRAZOMYCINS): INITIAL CLINICAL TRIAL

Pyrazofurin* (PF)’*2 is one of three biologically active C-nucleosides isolated from the broth filtrates of a strain of Streptomyces candidus. Along with PF, this culture produces lesser amounts of its C1,-a-anomer, Pyrazofurin B (PFB),3*4 and a third factor, tentatively identified as OxazinomycinS (Minimycin).6 Among these and the four other naturally occurring C-nucleosides, PF alone enjoys the distinction of possessing pharmacological activity that warrants its consideration as a clinical candidate.

Biosynthesis of uridine-5'-monophosphate in rat liver and Morris hepatomas.

Abstract The enzymes that synthesize UMP from aspartate and carbamyl phosphate were characterized with respect to optimum pH and Km, and their activities in the MOrris hepatomas 7800, 5123D, 7288C, 3924A and 3683. The enzyme activities were compared to the growth rates of the hepatomas. Carbamyl aspartate transferase, dihydroorotase and dihydroorotate amidohydrolase were the only enzyme activities that correlated with the growth rate of the hepatomas. Dihydroorotate dehydrogenase was equal to or lower than normal liver values, whereas orotate phosphoribosyl transferase and orotidylic acid decarboxylase activities were higher than the activities of the normal livers. No biochemically significant differences were observed between the pH optima or Kms of the normal livers and hepatomas. Four of the possible reversible enzyme reactions were studied. The conversion of OMP to orotate and dihydroorotate to ureidosuccinate were operative while ureidosuccinate to aspartate and orotate to dihydroorotate conversions were not detected. The role of phosphoribosyl pyrophosphate and carbamyl phosphate biosynthesis was discussed. Some potential areas of regulation were also mentioned.

Effects of acute insulin insufficiency on liver and adipose tissue fatty acid synthesis

Abstract Insulin deficiency of 1.5–3 hours duration induced in rats by anti-insulin serum (AIS) resulted in a reduction in the incorporation of C 14 from labeled pyruvate or acetate into fatty acids in liver slices. Fatty acid synthesis was also reduced in livers of hypophysectomized rats and AIS resulted in a further decrease in lipogenesis. Metabolism of C 14 -labeled pyruvate by isolated adipose tissue was not influenced by prior treatment with AIS.