γ-VINYL GABA: EFFECTS OF CHRONIC ADMINISTRATION ON THE METABOLISM OF GABA AND OTHER AMINO COMPOUNDS IN RAT BRAIN

Rats were given γ-vinyl GABA (4-amino-hex-5-enoic acid), a new irreversible inhibitor of GABA aminotransferase (GABA-T), by daily subcutaneous injection (100mgkg) for 11 days. Amino acids were quantitated in the brains of the γ-vinyl GABA-treated and control animals 24 h after the last injection, and enzyme activities of GABA-T and glutamic acid decarboxylase (GAD) were measured. Chronic administration of γ-vinyl GABA produced a 150% increase in brain GABA content, along with marked increases in the contents of B-alanine and homocarnosine. Brain GABA-T activity was reduced by 26%, and GAD activity was reduced by 22%. In addition, γ-vinyl GABA caused a marked increase in hypotaurine content in rat brain, suggesting that it acts as an inhibitor of hypotaurine dehydrogenase, and it produced significant decreases in brain contents of glutamine and threonine. Although it is an effective GABA-T inhibitor, γ-vinyl GABA apparently affects several other brain enzymes as well, and it may not be an ideal drug for elevating brain GABA levels in man.     

rDNA magnification in D. melanogaster: state of rDNA copies following the first step.

Summary D. melanogaster males of bb/O genetic constitution undergoing rDNA magnification were mated singly to XXbb ⁺/O females, yielding bb/O male progeny, and to X_NO-w sn bb ⁺ fameles, yielding bb/X_NO- females. The male and female offspring were scored for the bb ⁺ phenotype.Results show that there is a higher percentage of bb ⁺ flies in the bb/O male progeny than in bb/X_NO- females progeny, in single crosses as well as in the combined data. rRNA/DNA hybridization experiments agree with this observation, by showing that the rDNA content in the progeny of premagnified flies was higher in the sons than in the daughters.These data indicate that the increase of ribosomal RNA genes is not due to a stable event such as an unequal mitotic sister exchange, whereas they do not contrast with the extracopy model.     

Sexual development of patients with isochromosomes for the long arm of the X chromosome

Summary The sexual development of 14 girls with non-mosaic monocentric 46,X,iXq karyotype was studied. Seven out of eight girls were found to have immature secondary sexual characteristics and amenorrhoea, a finding greatly contrasting with that in Triplo-X girls. The relative ineffectiveness of the isochromosome Xq in maintaining fertility may be due to the absence of one short arm, which probably also carries a gonadal determinant. Alternatively, the presence of two inactivation sites on one isochromosome may render the gonadal determinants inactive at an important stage in gonadal development.     

I-A Mutation resulted in a selective loss of an antigen-specific Ir gene function

The immune responses to several antigens were compared in the I-A mutant mouse strain B6.C-H-2^bm12 and the wild-type strain C57BL/6. With a lymph node cell proliferation assay, the response to two of these antigens, beef insulin and (TG)A-L, was demonstrated to be controlled by a gene in the I-A^b region. B6.C-H-2^bm12 mice failed to respond to beef insulin, while their responses to (TG)A-L, DNP-OVA and PPD were comparable with those of the wild-type strain C57BL/6. Taken together with previous studies, these data suggest that the product of a single pleiotropic I-A gene, an la molecule, functions as a histocompatibility, la, and MLR antigen, as well as a necessary component for Ir gene function. Furthermore, the data reported here demonstrate that la molecules have multiple functional “Ir determinants,” one of which has been altered in the B6.C-H-2^bm12 mutant. The B6.C-H-2^bm12 mice, therefore, represent a powerful analytical tool for the understanding of the cellular and molecular basis for Ir gene control of the immune response.     

The identification of Tithonia voucher specimens used for sesquiterpene lactone investigations

The identification of Tithonia voucher specimens as T. rotundifolia (Mill.) Blake, used for sesquiterpene lactone chemical investigations, have been found to be T. diversifolia (Hemsl.) A. Gray. The compound Ivalin, also is reported for the first time from T. calva Sch. Bip. in Semann.     

Metabolism and transport of glutamine and glucose in vascularly perfused small intestine of the rat

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.     

Aldolase-like imine formation in the mechanism of action of phosphonoacetaldehyde hydrolase.

Phosphonoacetaldehyde hydrolase (EC 3.11.1.1), the bacterial enzyme that catalyses the reaction HCO-CH2-PO(OH)2+H2O leads to HCO-CH3+Pi, is inactivated by borohydride if either phosphonoacetaldehyde or acetaldehyde is present. This supports the suggestion that the substrate forms an imine with an amino group of the enzyme. Such imine formation would labilize the C-P bond in the same way that aldolase and related enzymes labilize C-C and C-H bonds (Scheme 1a).     

Virus-like particles in the brown algaStreblonema

Summary Ultrastructural examination ofStreblonema sp. revealed icosahedral virus-like particles (135–150 nm) throughout the cytoplasm of vegetative cells. The densely packed particles consist of an osmiophilic coat around a fibrillar core. Most cytoplasmic organelles are excluded from the regions where the particles are extremely abundant, but no degeneration of plastids, mitochondria or dictyosomes is evident. The virogenic stroma contains many ribosomes and fibers possibly representing DNA strands remaining from the lysed nucleus. No decrease in vigor seemed to be associated with the presence of the particles.     

BIOCHEMICAL EFFECTS IN MAN and RAT OF THREE DRUGS WHICH CAN INCREASE BRAIN GABA CONTENT

Abstract— Brain amino acids were measured in rats given aminooxyacetic acid (AOAA) by mouth, and in rats given sodium dipropylacetate (DPA) both orally and by intraperitoneal injection. Brain GABA content was significantly elevated by AOAA doses of 10mg/kg/day, but not by 5mg/kg/day. Approximately 4 times as much AOAA is required by mouth as by parenteral injection to raise brain GABA content in the rat. DPA (400mg/kg) increased brain GABA and lowered brain aspartate content significantly 1 h after a single injection. However, DPA given orally (350 mg/kg/day) produced no alterations of any amino acids in rat brain.
Amino acids were measured in plasma and urine from patients treated orally with isonicotinic acid hydrazide (INH) or DPA, and from a volunteer who took AOAA. INH (10–21 mg/kg/day) increased concentrations of β -alanine and ornithine in plasma, as well as urinary excretion of β -alanine. DPA had no such effect. AOAA in oral doses ranging from 1.25 to 5.0 mg/kg/day increased plasma concentrations of β -alanine, ornithine, β -aminoisobutyric acid, proline and hydroxyproline, and produced massive urinary excretion of β -alanine, β -aminoisobutyric acid, and taurine.
Both INH and AOAA, given in doses practical for human use, inhibit the transamination of β -alanine and ornithine in liver, and may also inhibit the transamination of GABA in brain. In addition, AOAA interferes with the catabolism of β -aminoisobutyric acid, proline, and hydroxyproline. AOAA, in the lowest dose employed, appeared more effective than INH as an inhibitor of GABA aminotransferase in man, and might therefore be useful in the treatment of neurological diseases in which brain GABA is deficient.