Hemin feedback inhibition at reticulocyte δ-aminolevulinic acid synthetase and δ-aminolevulinic acid dehydratase

Addition of hemin (5–200 μM) to a rabbit reticulocyte iron-free incubation medium, resulted in a progressive inhibition of heme synthesis as measured by incorporation of (¹⁴C)-glycine. In contrast when (¹⁴C) δ-aminolevulinic acid incorporation into heme was studied, significant inhibition below that of the (¹⁴C)-glycine control only occurred with hemin concentrations greater than 100 μM. Hemin progressively inhibited cellular and mitochondrialδ-aminolevulinic acid synthetase activity, as well as cellular δ-aminolevulinic acid dehydratase activity. The results indicated that elevated levels of hemin initially control heme synthesis by feedback inhibition at the rate-limiting enzyme of heme synthesis, δ-aminolevulinic acid synthetase. Hemin inhibition of δ-aminolevulinic acid dehydratase is only significant for the entrire heme synthetic pathway when greater than one-third of this enzyme's activity is inhibited.     

Reactions of 3-(1-arylhydrazono-L-threo-2,3,4-trihydroxybutyl)-1-methyl-2-Quinoxalinones

The 1-methyl derivatives (3 and 4) of 3-(1-phenyl- (1) and 3-(1-p-bromophenylhydrazono-L-threo-2,3,4-trihydroxybutyl)-2-quinoxalinone (2) were prepared by methylation. Periodate oxidation of 3 gave 1-methyl-3-[1-(phenylhydrazono)glyoxal-1-yl]-2-quinoxalinone (5), which, on reduction with sodium borohydride, gave the corresponding 3-[2-hydroxy-1-(phenylhydrazono)ethyl] derivative (8). Reaction of 5 with hydroxylamine or benzoylhydrazine gave the corresponding 2-oxime (6) and 2-(benzoylhydrazone) (7), respectively. Acetic anhydride causes one molecule of 3 or 4 to undergo elimination of two molecules of water, with simultaneous acetylation and ring closure to afford pyrazoles 9 and 10, respectively. Pyrolysis of the triacetate of 3 led to the elimination of acetic acid from the sugar and the hydrazone residue, to give the 3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl] derivatives (9). Acetic acid was found to effect the same rearrangement, but without acetylation, of 1, 2, and 3 to give the 3-[5-(hydroxymethyl)] derivatives 11, 12, and 13, respectively. The structure of these pyrazoles was confirmed by a series of reactions, including methylation and acetylation. The n.m.r. and i.r. spectra of the compounds were investigated.     

Phenolic synthesis in Perilla cell suspension cultures

Suspension cultures of Perilla ocymoides accumulate caffeic acid, both in free and ester forms, as the only phenylpropanoid end metabolite. Increased levels of growth substances influenced the levels of PAL activity and phenolic accumulation so that cytokinin stimulated, while auxin repressed both parameters. The regulatory role of caffeyl compounds is discussed in relation to their accumulation during the early exponential phase of culture growth.     

Glycogenosis in the Dog

Four cases of a generalized form of glycogenosis occurring in German Shepherd dogs, all females, are described. Symptoms could be noticed as early as the age of two months and progressed slowly for months. They appeared as dizziness, muscular weakness, and in two of the cases as poor nutritional state. The abdomen became gradually distended. The main lesion seen at postmortem was a greatly increased liver size with some moderate liver fibrosis. Heavy deposits of a granular substance behaving as glycogen in histochemical tests and at electron microscopy were found in the hepatic cells, muscle fibres of the heart, skeletal and smooth muscles, and in nerve and glial cells of the central nervous system. The substance was lying freely dispersed in the cell cytoplasm without any indication of lysosomal storage. The disease of dogs does not seem to be fully comparable with any of the types observed in man, but is probably much related to Type III or Cori's Disease. Structure analysis of the deposits and enzyme investigations have been done and are published (Čeh et al. 1976).     

Anthropological studies among Libyans. Erythrocyte genetic factors,serum haptoglobin phenotypes and anthropometry

Anthropological studies were done on 1276 Libyans from the Mediterranean cities of Tripoli and Benghazi, and from Sabha southward in The Sahara. The incidences of hemoglobin (Hb)-S and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were low in the coastal areas and significantly high in Sabha. Hb-C occurred sporadically in Tripoli and Sabha, and was absent from Benghazi in the east. One case of Hb-J Benghazi was noted. There were no significant differences in the ABO blood group and Rh₀ (D) type distributions in the three localities. G-6-PD gene Gd^A frequency was significantly high in Sabha. The lowest value of 6-phosphogluconate dehydrogenase (6-PGD) gene PGD^A frequency and highest value of the gene PGD^C were in Sabha. Adenylate kinase (AK) gene AK² was only detectable in Tripoli. Acid phosphatase (AP) gene P^a frequency in Sabha was more than twice that in Tripoli and Benghazi, while P^c was distinctly lower in Sabha than in the northern cities. Haptoglobin gene Hp¹ frequency was almost identical in all areas. Anthropometric measurements revealed overall homogeneity of the three samples, closer similarity in the coastal region to adjacent North African populations, and Negroid influence in the Saharan Libyans. Anthropometry substantiated findings from blood markers.     

Studies on the antibacterial effects of negapillin in combination with other antibiotics and sulfa drugs

Summary The antibacterial effect of negapillin in combination with other antibiotics and sulfa drugs was studied using Gram+ve and Gram-ve bacteria as test organisms. Subsequently, various proportions of negapillin in combination with the antibiotics and the sulfa drugs were examined to determine the optimum proportions which exert maximum inhibitory effects on the bacterial growth. Mixtures of these antibiotics with negapillin were found more superior not only as antimicrobial agents but also for having comparatively low toxicity.