Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male pseudohermaphroditism due to 5 alpha-reductase deficiency was clinically and biochemically described in a large Dominican kindred of 23 families with 38 affected subjects in 1974. Recently, the 5 alpha-reductase-2 gene defect in the large Dominican kindred was found to be due to a single base substitution of thymidine (TGG) for cytosine (CGG) on exon 5 of the 5 alpha-reductase-2 gene, causing a tryptophan replacement of arginine at amino acid 246 (R246W) of the enzyme. In the present report, affected subjects from four additional Dominican families were studied to determine whether they carried the same 5 alpha-reductase-2 gene defect as the large kindred, suggesting a common ancestry for the gene defect within this small country. Using single strand conformational polymorphism and DNA sequencing, two other mutations of the 5 alpha-reductase-2 gene were found in affected subjects from two of the four families. A point mutation on exon 2 of the 5 alpha-reductase-2 gene, in which substitution of adenine (GAC) for guanine (GGC) caused an aspartic acid replacement of glycine at amino acid 115 (G115D), was demonstrated in one of these families, and a substitution of adenine (AGT) for guanine (GGT) on exon 3 causing a serine replacement for glycine at amino acid 183 (G183S) was detected in the other family. Affected subjects from the two remaining families demonstrated the same exon 5 mutation of the 5 alpha-reductase-2 gene as previously detected in the large Dominican kindred. The phenotypic and biochemical characteristics of the male pseudohermaphrodites were similar regardless of the genetic defect, except that one affected subject (C-VI-2) with the same exon 5 mutation as the large Dominican kindred had much more facial and body hair. Thus, the identification of multiple mutations in the 5 alpha-reductase-2 gene in male pseudohermaphrodites from the Dominican Republic demonstrates a lack of common ancestry, as had been previously postulated.
 ...
PMID:5 alpha-reductase-2 gene mutations in the Dominican Republic. 862 25

The hepatic hemoprotein tryptophan 2,3-dioxygenase (TDO) is the key regulatory enzyme that, through irreversible degradation, controls the flux of tryptophan through physiologically relevant pathways. This enzyme is composed of four identical subunits and in its fully assembled tetrameric form requires 2 mol of heme (Fe(+2)-protoporphyrin IX)/mol of protein for functional competence. Using a full-length cDNA for the rat liver TDO subunit (pUC119/TDO) as the template, TDO cDNA was amplified by polymerase chain reaction (PCR) and incorporated into the expression vector pTrc99A after introduction of convenient restriction sites as well as modification of the second codon AGT to GCT to optimize its bacterial expression. DH5 alpha F' strain Escherichia coli cells transfected with this pTrc99A/TDO construct expressed soluble, functionally active, tetrameric TDO protein in high yields. The enzyme was isolated from 30,000g supernatant of cell lysates, purified by ion-exchange chromatography, and its spectral and catalytic properties were assessed in terms of its substrate and prosthetic moiety specificities. In almost all aspects, the bacterially expressed enzyme was found to be identical to that of the rat liver. Heterologous expression of the fully functional enzyme, we trust, will enable future elucidation of its structure-function relationships.
 ...
PMID:Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme. 880 58

This study describes the comparative analysis of two insect recombinant aminotransferases, Aedes aegypti 3-hydroxykynurenine (3-HK) transaminase/alanine glyoxylate aminotransferase (Ae-HKT/AGT) and Drosophila melanogaster serine pyruvate aminotransferase (Dm-Spat), which share 52% identity in their amino acid sequences. Both enzymes showed AGT activity. In addition, Ae-HKT/AGT is also able to catalyze the transamination of 3-HK or kynurenine with glyoxylate, pyruvate or oxaloacetate as the amino acceptor. Kinetic analysis and other data suggest that Ae-HKT/AGT plays a critical role in mosquito tryptophan catabolism by detoxifying 3-HK and that Dm-Spat is primarily involved in glyoxylate detoxification.
 ...
PMID:Comparative characterization of Aedes 3-hydroxykynurenine transaminase/alanine glyoxylate transaminase and Drosophila serine pyruvate aminotransferase. 1222 Jun 60

In the mosquito, transamination of 3-HK (3-hydroxykynurenine) to XA (xanthurenic acid) is catalysed by an AGT (alanine glyoxylate aminotransferase) and is the major branch pathway of tryptophan metabolism. Interestingly, malaria parasites hijack this pathway to use XA as a chemical signal for development in the mosquito. Here, we report that the mosquito has two AGT isoenzymes. One is the previously cloned AeHKT [Aedes aegypti HKT (3-HK transaminase)] [Han, Fang and Li (2002) J. Biol. Chem. 277, 15781-15787], similar to hAGT (human AGT), which primarily catalyses 3-HK to XA in mosquitoes, and the other is a typical dipteran insect AGT. We cloned the second AGT from Ae. aegypti mosquitoes [AeAGT (Ae. aegypti AGT)], overexpressed the enzyme in baculovirus/insect cells and determined its biochemical characteristics. We also expressed hAGT for a comparative study. The new cloned AeAGT is highly substrate-specific when compared with hAGT and the previously reported AeHKT and Drosophila AGT, and is translated mainly in pupae and adults, which contrasts with AeHKT that is expressed primarily in larvae. Our results suggest that the physiological requirements of mosquitoes and the interaction between the mosquito and its host appear to be the driving force in mosquito AGT evolution.
 ...
PMID:Evolution of two alanine glyoxylate aminotransferases in mosquito. 1668 62

Grafting has been reported as a factor that influences fruit quality. However, a comprehensive study of the metabolic profile related to fruit quality and the underlying molecular mechanism in grafted watermelon has not been carried out. Metabolomics and transcriptome analysis were performed on both pumpkin-grafted watermelon and ungrafted watermelon at different developmental stages. In total, 56 primary metabolites were identified with either high or low abundance between ungrafted and pumpkin-grafted watermelon. The results indicated that ornithine, arginine, lysine (amino acids), glucose, sucrose, glucosamine (sugars), malic acid, fumaric acid and succinic acid (organic acids) were among the dominant metabolites influencing fruit quality. Additionally, comparative RNA sequence analysis on grafted and ungrafted watermelon yielded 729, 174, 128 and 356 differentially expressed genes at 10, 18, 26 and 34 days after pollination (DAP), respectively. Functional annotations of these genes indicated that grafting significantly altered the biological and metabolic processes related to fruit quality. Our comparative metabolomics and transcriptome analysis revealed that FBA2, FK, SuSy, SPS, IAI, AI and sugar transporter gene (SWT3b) might play a central role in the accumulation of glucose and sucrose, whereas higher malic acid content was attributed to high down regulation of ALMT13 and ALMT8 in pumpkin-grafted watermelon. Changes in the ornithine, glutamine, alanine, tyrosine, valine, asparagine, phenylalanine, arginine and tryptophan contents were consistent with the transcript level of their metabolic genes such as NAOD, GS, AGT, TaT, aDH1, OGDH, aDC, 4CL 1, PaL, CaT and two nitrate transporter genes (NRT1) in pumpkin-grafted watermelon. This study provides the basis for understanding the graft-responsive changes in the metabolic profile and regulatory mechanism related to fruit quality.
 ...
PMID:Comparative analysis of primary metabolites and transcriptome changes between ungrafted and pumpkin-grafted watermelon during fruit development. 3193 3