The conversion of L-histidine to glutamic acid by liver enzymes

Edlbacher and Neber (1) showed in 1934 that the liver enzyme named histidase degrades histidine to NH3, formic acid, and an unknown product which on further treatment with strong alkali yields glutamic acid. This led to the suggestion that glutamic acid is a metabolic product of histidine, a suggestion that was supported by the finding that glycogen was formed from histidine about as well as from glutamic acid (2). These findings did not prove that glutamic acid was one of the products of histidine metabolism, and the idea became questionable when the evidence from subsequent investigations with non-isotopic histidine (3), imidazole-N16-histidine (4), and carboxyl-C14-histidine (5) were negative or inconclusive. In studies on the fate of carboxyl-C14-L-histidine in the liver of rabbits after injection and after incubation with guinea pig liver slices, we have found direct evidence that glutamic acid is a major product of histdine metabolism. Another highly radioactive compound was isolated by ion exchange chromatography, whose properties with respect to chromatography and lability to alkali and acid appear to correspond to those reported for isoglutamine. Takeuchi (6) isolated and identified isoglutamine as a product of the action of urocanicase on urocanic acid, which was obtained by the action of another liver enzyme on histidine. The formation of isoglutamine as an intermediate is consistent with our finding that the label in the radioactive glutamic acid formed from carboxyl-C14-histidine is not in the α-carboxyl group, and the inference is very strong that the label is in the γ-carboxyl group

Racism on Campus: An Exploratory Analysis of Black-White Perceptions in the South

Racism has been a persistent problem in American society. Sociologists refer to racism as unfair treatment of an individual or a group solely on the basis of race.[1] It may be covert or overt, and it may be expressed on an individual level when a person consciously or unconsciously discriminates against another person. Racism may also be expressed on an institutional level, when rules, policies and practices of organizations and/or institutions discriminate against an individual or a group.[2

Reclaiming Illinois strip coal lands by forest planting

Cover title.Bibliography: p. 240

The role of self-help groups in rural non-farm employment

Self- help groups (SHGs) play today a major role in poverty alleviation in rural India. A growing number of poor people (mostly women) in various parts of India are members of SHGs and actively engage in savings and credit (S/C), as well as in other activities (income generation, natural resources management, literacy, child care and nutrition, etc.). This paper attempts to identify the role of SHGs in providing Rural Non-Farm Employment (RNFE) through enterprise development and marketing

Effect of congenital reduced GCH1-function on sensitized and unsensitized pain

Hintergrund: Träger eines bestimmten Haplotyps des Gens der GTP Cyclohydrolase (GCH1) gaben im Anschluss an eine Diskektomie nach chronischer lumbaler Radikulopathie weniger Schmerzen an und hatten in experimentellen Schmerzmessungen höhere Schmerzschwellen. Die ex-vivo GCH1-Hochregulierung und BH4-Produktion nach Forskolinstimulierung war reduziert, während die Grundwerte der BH4-Konzentration nicht verändert waren. Diese Beobachtungen legen nahe, dass der Haplotyp hauptsächlich Veränderungen zeigt, wenn das GCH1-System provoziert wird. Diese Studie zielt darauf ab, (1) diese Hypothese zu testen und (2) die schmerzprotektiven Eigenschaften, die diesem Haplotyp zuvor zugeschrieben wurden in unabhängigen Rahmen zu reproduzieren. Methodik: Hierzu wurden experimentelle Schmerzmodelle mit Sensitisierung (lokale Hautentzündung, topische Capsaicinapplikation) und ohne Sensitisierung (punktuell-mechanischer Druck, stumpfer Druck, thermischer und elektrischer Schmerz) an 10 homozygoten Trägern und 22 homozygoten Nichtträgern des angeblich schmerzprotektiven GCH1-Haplotyps durchgeführt. GCH1-, iNOS-Hochregulierung und BH4-Produktion wurden ex-vivo in Leukozyten nach LPS-Stimulation für 24 Stunden ermittelt. Ergebnisse: Träger dieses GCH1-Haplotyps hatten höhere Schmerzschwellen für punktuell-mechanischen Druck (von Frey Haare) im Anschluss an eine lokale Hautentzündung (18.1 ± 11.3 vs. 9 ± 2.8 g; p = 0.005) und im kleineren Rahmen für thermischen Schmerz nach Hyperalgesieinduktion durch Capsaicincreme (35.2 ± 0.9 vs. 36.6 ± 2.4 _C; p = 0.026). Dem hingegen konnten bei den Schmerzmodellen ohne Sensitisierung keine genotypabhängigen Effekte beobachtet werden. GCH1-, BH4 und iNOS-Hochregulierung in Leukozyten nach 24-stündiger LPS-Stimulation waren vermindert bei Trägern des GCH1-Haplotyps, woraus sich schließen lässt, dass sich die Genotypgruppen im Hinblick auf die Regulationsvorgänge im Biopterinstoffwechsel unterscheiden. Schlussfolgerung: Diese Studie bestätigt die vorherigen Befunde, dass eine verminderte GCH1-Funktion oder GCH1-Induzierbarkeit als Folge von genetischen Polymorphismen einen schmerzprotektiven Effekt mit sich bringt. Als Erweiterung der Vorresultate zeigt diese Arbeit, dass sich der schmerzprotektive Effekt vorzugsweise in Schmerzmodellen mit Sensitisierung ausprägt. Dies legt eine besondere Rolle von BH4 bei spezifischen Schmerzprozessen nahe.Background: Carriers of a particular haplotype in the GTP cyclohydrolase gene (GCH1) had less pain after surgery for chronic lumbar radiculopathy and a decreased sensitivity to some experimental mechanical pain stimuli. Ex-vivo, GCH1 upregulation and BH4 production after forskolin stimulation were reduced, while baseline BH4 concentrations were not affected. This suggested that the haplotype may mainly exert its modulating function when the GCH1 system is provoked. The present study aimed at (1) testing this hypothesis and (2) independently reproducing the pain-decreasing effects of a particular GCH1 haplotype having been previously associated with pain protection. Methods: Experimental pain models with sensitization (local skin inflammation, dermal capsaicin application) and without sensitization (punctate pressure, blunt pressure, thermal and electrical pain) were assessed in 10 homozygous and non-carriers of the particular GCH1 haplotype reportedly associated with pain protection. GCH1, iNOS upregulation and BH4 production were assessed ex-vivo in white blood cells after lipopolysaccharide stimulation for 24 h. Results: Carriers of the particular GCH1 haplotype addressed in this study had higher thresholds to punctate mechanical pain (von Frey hairs) following local skin inflammation (18.1 ± 11.3 vs. 9 ± 2.8 g; p = 0.005) and, to a lesser degree, to heat pain following capsaicin sensitization (35.2 ± 0.9 vs. 36.6 ± 2.4 _C; p = 0.026). In contrast, heat and pressure thresholds and tolerance to electrical stimulation in pain models without sensitization did not differ among the genotypes. GCH1, BH4 and iNOS upregulation in white blood cells after lipopolysaccharide stimulation were decreased in carriers of the GCH1 haplotype, which verified that the genotype groups differed with respect to regulation of the biopterin pathway. Conclusions: This study verifies previous results that decreased GCH1 function or inducibility as a result of genetic polymorphisms protects against pain. This study extents previous results by showing that this pain protection is mainly conferred under conditions of hyperalgesia resulting from sensitization, supporting specific functions of BH4 in relation to particular aspects of pain