Disease relevance of Hal

• Rat histidase was found to have 41 and 43% amino acid identity to Pseudomonas putida and Bacillus subtilis histidases, respectively [1].
• A selected rat histidase cDNA clone was introduced into the pET-16b prokaryotic vector and expressed in BL21(DE3)pLysS Escherichia coli [2].
• During this period, undernutrition also significantly reduced Hal activity and Hal-mRNA concentration [3].
• These results indicate that rats fed a histidine-imbalanced diet exhibit reduced food intake and weight gain and increased Hal gene expression as a consequence of an increased amino acid catabolism [4].
• Activity levels of hepatic glutathione S-transferase, UDP-glucuronyltransferase, and aryl hydrocarbon hydroxylase are reduced to activity levels of control females, while histidase, 5 alpha-reductase, and serum cholinesterase levels are increased to levels of control females, i.e. feminization of all of these enzymes [5].

High impact information on Hal

• Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase [6].
• To determine whether serine may be the dehydroalanine precursor in rat histidase, we substituted four highly conserved serines with alanines, and expressed the mutated histidase cDNAs in COS cells, which have no endogenous histidase activity [7].
• Site-directed mutagenesis of conserved serines in rat histidase. Identification of serine 254 as an essential active site residue [7].
• We have identified serine 254 as an essential residue in rat histidase (histidine ammonia-lyase, EC 4.3.1.3) [7].
• Histidase (histidine ammonia-lyase, EC 4.3.1.3) catalyzes the deamination of histidine to urocanic acid [1].

Chemical compound and disease context of Hal

• Histidine ammonia-lyase (histidase) from Pseudomonas putida was irreversibly inactivated by L-cysteine at pH 10.5 in the presence of oxygen [8].

Biological context of Hal

• To identify the Hal gene regulatory region, a 1248-bp fragment of the 5'-region was obtained [9].
• The putative Hal promoter region was cloned into the pGL3basic vector and transfected into HepG2 cells [9].
• As an initial step to determining the precursor of dehydroalanine in histidase, we have isolated a functional cDNA clone for histidase from a rat liver cDNA library using an affinity-purified antiserum [1].
• Soy protein, casein, and zein regulate histidase gene expression by modulating serum glucagon [10].
• Whereas the initial description of the rat histidase 3' untranslated sequence contained a rare polyadenylation signal sequence, the data presented encompass a more distant 28-bp region, possessing a nucleotide stretch (AATATAAA), identical to that in the mouse histidase cDNA [2].

Anatomical context of Hal

• The addition of phorbol 12-myristate,13-acetate (PMA) and forskolin to hepatocytes increased Hal mRNA concentration by 100 and 40%, respectively [9].
• COS cells transfected with a histidase expression vector produce active histidase [1].
• Among other histidase-positive cells were those of the renal cortex tubular epithelium, fundic mucosal glands of stomach, gastric intramuscular (Auerbach's) plexus, and adrenal cortex [2].
• Six days after the injection rats were killed and hepatic Hal and skeletal muscle BCATm activities were measured [11].
• To determine whether changes in functional histidase mRNA levels underlie this developmental pattern, total cellular RNA was translated in a rabbit reticulocyte cell-free lysate system [12].

Associations of Hal with chemical compounds

• Histidase (Hal), the amino acid-degrading enzyme of histidine, is regulated by the protein content of the diet and by hormones such as glucocorticoids and glucagon [9].
• Histidase and phenylalanine ammonia-lyase are the only two enzymes that have been postulated to require the modified amino acid, dehydroalanine, for enzyme activity [7].
• Cloning and expression of rat histidase. Homology to two bacterial histidases and four phenylalanine ammonia-lyases [1].
• Estrogen does not induce hepatic histidase in the hypophysectomized rat [13].
• Treatment of hypophysectomized rats with physiological levels of triiodothyronine (T3) diminished histidase synthetic rates and catalytic activities to normal levels, despite concomitant elevation in total soluble protein synthesis [13].

Other interactions of Hal

• Thus the type and amount of protein consumed affect Hal activity and expression through changes in serum glucagon concentrations [10].
• However, administration of the histidase suppressor, T3, or prolactin, which in itself has no effect on this enzyme, was ineffective in reinstating estrogen inducibility of histidase in the hypophysectomized animal [13].
• Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver [14].
• Furthermore, VMH-lesions induced an increase in urea contents of the liver and serum, and elicited an increase in activity of liver tyrosine aminotransferase (TAT) and a decrease in activity of liver histidase [15].
• As expected, the hepatic activities of a number of enzymes involved in the catabolism of histidine to CO2 were markedly decreased in hyperthyroid (histidase, 69%; urocanase, 30%; 10-formyltetrahydrofolate dehydrogenase, 65%) and folate-restricted (10-formyltetrahydrofolate dehydrogenase, 44%) rats [16].

Analytical, diagnostic and therapeutic context of Hal

• Full-length cDNAs encoding rat histidase have been isolated from a lambdaZAP liver cDNA library using a partial cDNA fragment obtained by PCR [2].
• Nutritional rehabilitation with an 18 or 50% casein diet for 1 d initiated the restoration of Hal activity and mRNA concentration [3].
• Also, total mRNA from both tissues was isolated and Hal and BCATm mRNA expression were analyzed by Northern blot [11].
• Hepatic Hal activity increased significantly in nephrotic and pair fed rats by 59% compared to control group [11].
• Effects of hypophysectomy and triiodothyronine on de novo biosynthesis, catalytic activity, and estrogen induction of rat liver histidase [13].

References