Disease relevance of GART

• The electrostatic surface potentials of the human GART domain and Escherichia coli enzyme explain differences in the binding affinity of polyglutamylated folates, and these differences have implications to future chemotherapeutic agent design [1].
• The frequency of protease and reverse transcriptase (RT) gene mutations was determined in HIV-1 strains from 153 patients entering the CPCRA 046 (GART) study who were failing triple-drug regimens consisting of one protease inhibitor (PI) and two RT inhibitors [2].
• The GART domain was expressed in E. coli under the control of bacteriophage T7 promotor and isolated by a three-step chromatographic procedure [3].
• We have characterized two different mutations of the human androgen receptor (hAR) found in two unrelated subjects with androgen insensitivity syndrome (AIS): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS) [4].
• PAIS with a virtually normal male phenotype can present in adulthood with sexual dysfunction as well as infertility [5].

High impact information on GART

• Cloning and in vivo expression of the human GART gene using yeast artificial chromosomes [6].
• Gart and Nam give a simple score test of a zero true recessive-gene frequency for such situations [7].
• Dinucleotide repeat polymorphism at the D21S370 locus which flanks the PRGS (GARS)-PAIS (AIRS)-PGFT (GART) gene [8].
• Therefore, the accessory factor (AF-1) gene can be localized to a 150-kb region at the left (centric) end of the parental 540-kb GART YAC [9].
• In contrast, there is limited posttranslational control over GART and PEPC and close posttranslational control over uricase activity [10].

Biological context of GART

• Consequently, the GARS gene locus, assigned to chromosome 21, could be localized in subband 21q22.1 [11].
• An excess of GARS activity was found in regular trisomy 21 with a trisomy 21/normal ratio equal to 1.55 [11].
• The enzymatic activity of phosphoribosylglycinamide synthetase (GARS) has been studied in several cases of partial monosomies and full and partial trisomies 21 [11].
• Organization and conservation of the GART/SON/DONSON locus in mouse and human genomes [12].
• While GART is involved in purine biosynthesis, we find that SON shows the characteristics of "SR- type" proteins, which are involved in mRNA processing and gene expression [12].

Anatomical context of GART

• Nine of 12 cell lines analyzed contained an intact stretch of at least 110 kb of YAC DNA surrounding the GART gene, and one cell line contained at least 480 kb, but not the entire 590 kb, intact [13].
• We found strong over-expression of the purine biosynthesis gene GART (mean 3-fold) in fetal hearts with +21 and verified this result by northern blotting and real-time RT-PCR [14].
• Chinese hamster ovary (CHO) cell mutant purine auxotrophs deficient in GAR synthetase (Ade-C) or AIR synthetase plus GAR transformylase (Ade-G) activities were transfected with this human GART cDNA subcloned into a mammalian expression vector [15].
• Localization of neurons afferent to the optic tectum in longnose gars [16].
• SETTING: The donor insemination program at the Human Reproduction Unit at the Hospital of Cruces, Pais Vasco University. PATIENTS: Eighty-eight women (47 IUI and 41 pericervical insemination) with at least one patent fallopian tube and < 40 years of age [17].

Associations of GART with chemical compounds

• Glycinamide ribonucleotide transformylase (GART; 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2), an essential enzyme in de novo purine biosynthesis, has been a chemotherapeutic target for several decades [1].
• In contrast, the MAIS subject's hAR (R871G) has k(diss) values that are apparently normal for MB and methyltrienolone; in addition, the R871G hAR's ability to bind MB resists thermal stress better than the hAR from the PAIS subject [4].
• Establishing the functional consequences of androgen receptor mutations in vitro systems and correlating them with clinical presentation may ultimately provide an explanation for the variable clinical presentation of AIS and perhaps enable prediction of the response to androgen therapy in infants with PAIS [18].
• Mary Beth Pais, MNEd, RN, ONC, the recipient of the 1993 Nursing Economic$ Excellence Award, is clinical nurse manager, University of Pittsburgh Medical Center, Montefiore University Hospital, Pittsburgh, PA [19].

Other interactions of GART

• Here, analysis of 21q22.1-->q22.2 genomic sequence revealed that ITSN consists of 41 exons spanning approximately 250 kb and maps between GART and D21S325 [20].
• The enzyme activities appear to be associated with an expressed protein of 110 kDa, very similar to that of purified human GART trifunctional enzyme [15].
• Specifically, both genes are localized to the region of chromosome 21 containing the markers D21S58, D21S65, and GART and appear to be proximal to D21S58 [21].

Analytical, diagnostic and therapeutic context of GART

• The three-dimensional structure of the GART domain from the human trifunctional enzyme has been solved by X-ray crystallography [1].
• DESIGN: Meta-analysis of randomized controlled trials comparing treatments aided by GART, PART and vPART, and controls [22].
• Compared with controls, at 3 and 6 months GART increased the proportion of patients with viral load below detection by 11% [95% confidence interval (CI), 6-16], and 10% (95% CI, 5-16), respectively [22].
• Transfer of the human HPRT and GART genes from yeast to mammalian cells by microinjection of YAC DNA [23].
• In children undergoing initial resection, the risk for nephrectomy (as calculated by the methods described by Gart) was more than twice compared with those undergoing resection after chemotherapy (P = .012; odds ratio, 2.32; 95% confidence interval of 1.23 to 4.42) [24].

References