Disease relevance of GUT1

• The complex GKD is an Xp21 contiguous gene syndrome involving the glycerol kinase locus together with the adrenal hypoplasia congenita (AHC) or Duchenne muscular dystrophy (DMD) loci or both [1].
• Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue [2].
• This is in good agreement with X-ray studies [Hurley, T., et al. (1993) Science 259, 673-677] on the Escherichia coli glycerol kinase [3].

High impact information on GUT1

• One clone (142) showed 60% identity to the Bacillus subtilis glycerol kinase gene at both the DNA and amino acid sequence levels [2].
• Analysis of DNA from somatic cell hybrids carrying deleted X chromosomes, has shown that clone 142 detects homologous sequences between Xp21.2-p22.1 (the interval containing the locus responsible for glycerol kinase deficiency--GKD) [2].
• TFII-I by itself had little effect on a full-length fos promoter in baby hamster kidney cells, but it synergistically enhanced transcriptional activation by G-kinase I beta [4].
• VDACs are the binding sites for several cytosolic enzymes, including the isoforms of hexokinase and glycerol kinase [5].
• One type was deficient in glycerol kinase activity, whereas the other type was deficient in sn-glycerol 3-phosphate dehydrogenase activity [6].

Biological context of GUT1

• The carbon source regulation of GUT1 was studied using promoter-reporter gene fusions [7].
• Mutational analysis of the GUT1 promoter region showed that two upstream activation sequences, UAS(INO) and UAS(ADR1), are responsible for approximately 90% of the expression during growth on glycerol [7].
• The binding of hexo-/glucokinase and glycerol kinase to mitochondria via the channel forming protein, porin, in pancreatic islet beta-cells and adipocytes, was recently proposed to participate in nutritional signaling, glucose sensing, and the control of high-energy phosphate distribution and oxidative phosphorylation [8].
• Identification of a ferritin light chain pseudogene near the glycerol kinase locus in Xp21 by cDNA amplification for identification of genomic expressed sequences [9].
• We used cDNA amplification for identification of genomic expressed sequences (CAIGES) to identify genes in the glycerol kinase region of the human X chromosome [9].

Associations of GUT1 with chemical compounds

• In that mutant, transcript levels from GUT1 and GUT2 are highly attenuated compared with those of the wild-type parent when both are grown on glycerol-based medium [10].
• In Saccharomyces cerevisiae glycerol utilization is mediated by two enzymes, glycerol kinase (Gut1p) and mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p) [7].
• Disruption of GUT1 showed that the gene is required for growth on glycerol, but not on glucose or ethanol media [11].
• The 12 isomers of monoammine chromium(III) ATP have been used to probe the ATP binding sites of yeast 3-phosphoglycerate kinase and glycerol kinase from Candida mycoderma [3].
• The four deoxynucleoside diphosphates (dNDP) including deoxyadenosine diphosphate (dADP), deoxyguanosine diphosphate (dGDP), deoxycytidine diphosphate (dCDP), and deoxythymidine diphosphate (dTDP), were synthesized from the corresponding deoxynucleoside monophosphates (dNMP) using the purified AK, GK, CK, and TK, respectively [12].

Other interactions of GUT1

• According to enzyme activity and transcript analysis, synthesis of glycerol kinase is repressed by glucose, and derepression is ADR1-dependent [11].

Analytical, diagnostic and therapeutic context of GUT1

• We present experimental evidence that this kinetic is an artefact created by glycerol kinase activity [13].

References