Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary elliptocytosis (HE) Sp alpha I/74 is a disorder associated with defective spectrin (Sp) heterodimer self-association and an abnormal tryptic cleavage of the 80-kD alpha I domain of Sp resulting in increased amounts of a 74-kD peptide. The molecular basis of this disorder is heterogeneous and mutations in codons 28, 46, 48, and 49 (codons 22, 40, 42, and 43 in the previous nomenclature which did not include the six NH2-terminal amino acids) have been reported. In this study we present data on seven unrelated HE Sp alpha I/74 kindred from diverse racial backgrounds in whom we identified four different mutations all occurring in exon 2 of alpha Sp at codon 28. Utilizing the polymerase chain reaction we established a CGT----CTT; Arg----Leu 28 mutation in one kindred of Arab/Druze origin. In two unrelated white kindred of English/European origin the substitution is CGT----AGT; Arg----Ser 28 and in two apparently unrelated white kindred from New Zealand, the mutation is CGT----TGT; Arg----Cys 28. Finally, in one American black kindred and in a black kindred from Ghana the mutation involves CGT----CAT; Arg----His 28. Allele specific oligonucleotide hybridization confirmed that the probands are heterozygous for the respective mutant alleles. All four point mutations abolished an Aha II restriction enzyme site which allowed verification of linkage of the mutation with HE Sp alpha I/74. Our results imply that codon 28 of alpha Sp is a "hot spot" for mutations and also indicate that Arg 28 is critical for the conformational stability and functional self association of Sp heterodimers.
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PMID:Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis. 167 39

A deficiency of activity of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT,EC 2.6.1.44)has been found in the livers of six patients with primary hyperoxaluria type 1 (PH), including three in whom the tissue was obtained by percutaneous needle biopsy. AGT activity, assayed in unfractionated liver tissue, ranged from 11 to 47% of the mean control value, and appeared to be related to the clinical severity of PH and to several biochemical variables which indicate the degree of pathophysiological derangement. There was no difference between patients and controls in the activities of glutamate: glyoxylate aminotransferase (GGT, EC 2.6.1.4) or catalase (EC 1.11.1.6). In the five most severe cases residual AGT activity could be largely accounted for by the crossover from another enzyme, presumably GGT. PH can be diagnosed using percutaneous hepatic needle biopsy and assay of AGT, whose activity may be useful in determining the prognosis and likely severity of the disease.
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PMID:Enzymological diagnosis of primary hyperoxaluria type 1 by measurement of hepatic alanine: glyoxylate aminotransferase activity. 288 Jan 11

The subcellular localization of alanine-glyoxylate aminotransferase (EC 2.6.1.44 L-Alanine: glyoxylate aminotransferase) of adult human liver was examined by sucrose density gradient centrifugation. The enzyme sedimented at the same density as catalase, indicating that it was localized in the peroxisomes. Alanine-glyoxylate aminotransferase activity in the liver of patients with cirrhosis was about 65% of that of normal liver or 71% of that from patients with chronic hepatitis, but its activity in the serum of patients with cirrhosis was higher than that from patients with chronic hepatitis. Patterns of activity of alanine-glyoxylate aminotransferase in liver and serum differed from those of aspartate-2-oxoglutarate aminotransferase and ornithine carbamoyltransferase that have a different intracellular location. Serum immunoreactive alanine-glyoxylate aminotransferase (Im-AGT) was measured by enzyme-linked immunoadsorbent assay (ELISA). The Im-AGT levels (mean +/- SEM) in acute (80 +/- 13 micrograms/L) and chronic (72 +/- 4 micrograms/L) hepatitis were higher than those of normal controls (44 +/- 1 micrograms/L). However, the difference between acute and chronic hepatitis was not statistically significant. The level in liver cirrhosis (54 +/- 3 micrograms/L) was lower than those of the hepatitides but higher than that of normal controls. The apparent half-life of serum Im-AGT of patients who underwent liver lobectomy by a microwave tissue coagulation method was approximately 3-4 days.
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PMID:Peroxisome localized human hepatic alanine-glyoxylate aminotransferase and its application to clinical diagnosis. 405 44

In the liver biopsy from an 8.5-year-old girl with the biochemical characteristics of rhizomelic chondrodysplasia punctata (RCDP), but with normal limbs, normal catalase-containing peroxisomes were absent. Light microscopy after diaminobenzidine staining for catalase activity (the peroxisomal marker enzyme) and immunostaining against catalase protein indicated a cytosolic localization of the enzyme. By electron microscopy, rare and extremely large, irregularly shaped vesicles were found in the parenchymal cells. The three peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, bi(tri)functional enzyme, and 3-ketoacyl-CoA thiolase) and alanine-glyoxylate aminotransferase were immunolocalized in these organelles. However, a weak to negative label was obtained after staining against catalase. Diaminobenzidine staining demonstrated a minimal catalase reaction product in some vesicles only. Morphometry revealed a corrected mean d-circle of 1.44 microns and a maximum d-circle of 2.767 microns (controls: 0.635 microns and 1.027 microns, respectively). Numerical, volume, and surface densities were reduced to 3%, 41%, and 17% of control values, respectively. The large size, irregular shape, and rarity of the organelles are morphologic features of peroxisomal "ghosts." It seems that in this patient, apart from the known peroxisomal defects in RCDP, catalase incorporation into the peroxisomes is impaired together with a normal proliferation (division) of the organelles. In the cultured skin fibroblasts from the patient, however, immuno-electron microscopy showed normal catalase-containing peroxisomes in apparently normal numbers.
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PMID:Cytoplasmic catalase and ghostlike peroxisomes in the liver from a child with atypical chondrodysplasia punctata. 812 28

A series of deletion constructs of the 5' flanking region of rat c-mos gene was positioned upstream to the CAT gene and transfected into muscle and non-muscle cells. CAT activities revealed that a region located downstream of a TATA box and containing the proximal transcription start site is the muscle c-mos promoter. This promoter is more efficient in L6 alpha 1 myoblasts than in L6 alpha 1 myotubes but not in C3H10T1/2 cells. Gel shift assays demonstrated that nuclear proteins from myoblasts and myotubes formed complexes migrating differently. Footprinting analyses showed that nuclear proteins from L6 alpha 1 myoblasts protected a DNA fragment located at position nt -979 to nt -938 relative to the first ATG of the rat c-mos ORF while nuclear proteins from myotubes protected the DNA between nt -998 to nt -928. Furthermore one of protein - DNA complexes containing the proximal transcription start site, included a consensus sequence TGTC(AGT/TCG)CC(A/T)G present in the initiator element (Inr) of several genes. Southwestern blot analysis pointed to a 82kDa polypeptide as a potential candidate for trans acting factor in myoblasts. In L6 alpha 1 myotubes this polypeptide is replaced by other proteins of 40-42kDa and 82kDa. An interplay between these two complexes may constitute a developmental as well as a physiologically regulated mechanism that modulates c-mos expression during the early stages of myogenesis.
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PMID:Identification of a cis acting element responsible for muscle specific expression of the c-mos protooncogene. 844 78

The dominant position among oxidoreduction processes in peroxisomes is ascribed to catalase, a number of aerobic oxidases, and Cu,Zn-superoxide dismutase. The peroxidase reaction of catalase requires substrates for hydrogen donation, other than H2O2, e.g. alcohols, aldehydes, formic acid. The peroxisomes contain an alternative system of beta-oxidation of higher carboxylic acids which in some types of plant cells is functionally very closely associated with the glyoxylate cycle. Regarding the role of peroxisomes in the metabolism of carboxylic acids, a very important finding has taken place, namely that besides acyl-CoA synthetase which is specific for long chains, the peroxisomes contain still another enzyme which allows the synthesis of CoA esters of fatty acids with very long chains. It is assumed that the entry of acyl-CoA esters or fatty acids into the perxisomes is performed by means of pores in membranes or acyl-carnitine transferases. Peroxisomes oxidize a very wide scale of substrates and contain several types of acyl-CoA oxidases: palmitoyl-CoA oxidase, pristanoyl-CoA oxidase, trihydroxy-coprostanoyl-CoA oxidase. The second and third reactions of peroxisomal beta-oxidation are catalyzed by the so-called three-functional enzyme, the activities of which are identical to those of 2-enoyl-CoA hydratase, beta-hydroxyacyl-CoA dihydrogenase and enoyl-CoA isomerase. The peroxisomes sufficiently oxidize dicarboxylic acids with a higher number of carbons beginning with the adipic acid. The peroxisomal system of beta-oxidation is utilized in metabolism of prostaglandins, pristanic acid-being the product of phytanic acid alpha-oxidation, and cholesterol. Several enzymatic activities needed for the synthesis of cholesterol partially take place in peroxisomes. The peroxisomes represent a decisive compartment for the initial phases of synthesis of plasmalogens. They contain the following enzymes: NAD(+)-glycerol-P-dehydrogenase, dihydroxyacetone-3-P-acyl-transferase, alkyl-dihydroxyacetone-P synthetase and acyl/alkyl-dihydroxyacetone-P reductase. The metabolism of amino acids takes place under the effect of peroxisomal enzymes--oxidase of diamino acids, D-aspartate oxidase, oxidase of L-pipecolic acid and alanine-glyoxylate aminotransferase. Only a few published sources consider it obvious that liver peroxisomes participate in degradation of spermine and spermidine. Polyamine oxidase oxidizes spermine resulting in the origin of spermidine and 3-aminopropionaldehyde, and spermidine is oxidized to putrescine and 3-aminopropionaldehyde. Peroxisomes in many phylogenetically lower animal species enable the break down of purine bases to urea and glyoxylic acid. In phylogenetically higher primates and in man, the activities of urate oxidase in peroxisomes are absent. (Fig. 14, Ref. 166).
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PMID:The role of peroxisomes in intermediary metabolism. 855 58

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.
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PMID:Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. 877 41

Recent clinical studies using neutralizing antibodies point to a key role for tumor necrosis factor-alpha (TNF-alpha) in chronic inflammatory diseases. Antisense technique is a recent approach aiming at inhibition of single proteins. Previously, we described nonspecific induction of TNF by phosphorothioate oligonucleotides. In this study, we established an in vitro model that allows specific inhibition of TNF synthesis, bypassing TNF induction. Freshly isolated human monocytes were incubated with oligonucleotides and the cationic lipid lipofectin in different ratios. TNF synthesis was stimulated with lipopolysaccharide and quantified by a specific radioimmunoassay (RIA). Among all sequences tested, one of the antisense oligonucleotides complementary to the translation initiation region of TNF mRNA (5'-CAT GCT TTC AGT CAT-3') revealed highest efficacy. At 2 microM, the antisense oligonucleotide inhibited TNF synthesis by up to 79%. A concentration as low as 250 nM of the antisense oligonucleotide was effective. Scrambled controls and controls with different, defined degrees of mismatches confirmed a sequence-specific action. Examination with confocal fluorescence microscopy showed a marked difference comparing lipofectin-mediated vs. spontaneous uptake. This study defines criteria that from the prerequisite necessary for design and application of antisense oligonucleotides against TNF in vivo.
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PMID:Specific suppression of human tumor necrosis factor-alpha synthesis by antisense oligodeoxynucleotides. 901 65

Mutant catalase cDNAs from the hypocatalasemic and acatalasemic mice were cloned and expressed in bacteria. A novel missense mutation, Asp (AAT) to Ser (AGT), was identified at amino acid position 439 of the hypocatalasemic catalase. Analysis of recombinant catalase mutants revealed that the mutation is responsible for the reduced activity of hypocatalasemic catalase and the unstable tetrameric structure of acatalasemic catalase was also suggested.
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PMID:cDNA cloning and expression of mutant catalase from the hypocatalasemic mouse: comparison with the acatalasemic mutant. 1177 37

With the aim to investigate association of polymorphisms of candidate genes with clinical peculiarities of hypertensive disease in patients having burdened familial anamnesis we examined 413 (229 men and 184 women, mean age 60.3 +/- 0.59 years) patients with essential arterial hypertension (AH). Determination of alleles and genotypes of polymorphic markers of ACE, AGT, AT2R1, CYP11B2, NOS3, ENDl, GNB3, PPARA, PPARG2, MTHFR, CAT, SOD2, PON1, PON2 sigma APOB, APOE, LPL genes was carried out with the use of polymerase chain reaction. Patient with AH having hereditary load were younger (58.9 +/- 0.75 and 61.3 +/- 0.89 years, respectively, p=0.017) and had significantly lower age of debut of the disease (44.4 +/- 0.84 and 47.5 +/- 1.03 years, respectively; p=0.013), higher values of systolic (204.8 +/- 7.66 and 187.0 +/- 2.04 mm Hg; p=0.032) and diastolic (111.2 +/- 1.05 and 107.3 +/- 1.17 mm Hg, respectively; p=0.025) arterial pressure (AP) compared with patients with AH without hereditary loaded anamnesis. Portion of patients with 3 degree of severity of AH was higher among patients with "familial" AH (53.6 and 44.1%, respectively, p=0.018). Early debut (in the age younger than 45 years in men and 55 years in women) was associated with carriage of genotype TT of polymorphic marker C825 of GNB3 gene (OR 2.65 95CI [1.27-5.54], p=0.005) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 1.67 95% CI [1.03-2.77], p=0.024). Higher AP level corresponding to 3-rd degree AH in the group of patients with burdened familial anamnesis was associated with carriage of Asn allele of polymorphic marker Lysl98Asn of EDN1 gene (OR 2.24 95% CI [1.20-4.18], p=0.008), 4a allele of polymorphic marker 4a/4b of NOS3 gene (OR 2.23 C/[1.29-3.83], p=0.002), genotype ArgArg of polymorphic marker Glnl92Arg of PON1 gene (OR 6.14 C7[1.46-25.67], p=0.01), T allele of polymorphic marker of C825T gene GNB3 (OR 1.75 C/[1.11-2.76], p=0.01) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 2.61 C/11.29-5.34], p=0.005). In patients without burdened familial anamnesis 3-rd degree AH was associated with higher frequency of allele Ala of polymorphic marker Pro12A1a of PPARG2 gene.
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PMID:[Association of genetic factors with clinical peculiarities of hypertensive disease in patients with burdened familial anamnesis]. 1925 15


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