Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human glycerol kinase gene family consists of at least six genomic loci, four of which encode expressed sequences. The X-linked gene responsible for GKD maps to Xp21.3. Analysis of cosmid and YAC clones shows that this locus is in excess of 50 kbp, and is comprised of 19 exons. In contrast, the remaining members of the gene family, on chromosomes 1, 4 and Xq, appear to be organized as intronless genes. Northern analysis shows expression of GK transcripts of three sizes in a wide range of adult tissues. Only the smallest hybridizing species is present in testis where it occurs at an elevated level. Two different testis transcripts have been identified and both of these originate from chromosome 4.
Hum Mol Genet 1994 Aug
PMID:The glycerol kinase gene family: structure of the Xp gene, and related intronless retroposons. 798 8

cDNA clones from a human adult testis cDNA library were isolated and sequenced as part of a programme to produce expressed sequence tags (ESTs). ESTs were used routinely to search DNA and protein sequence databases. One clone (142) showed 60% identity to the Bacillus subtilis glycerol kinase gene at both the DNA and amino acid sequence levels. 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). These sequences are deleted in two patients with GKD. Clone 142 also detects homologous sequences on Xq and at several autosomal loci. The sequences of clone 142 and two further cDNA clones isolated from a human foetal brain cDNA library are presented.
Hum Mol Genet 1993 Feb
PMID:Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue. 849 11

Glycerol kinase is an X chromosome-encoded enzyme involved in the metabolism of endogenous and dietary glycerolipids. The physiological significance of its activity in mammals is not well understood. Glycerol kinase deficiency in humans occurs as an isolated enzyme deficiency or as part of a contiguous gene deletion syndrome in variable association with Duchenne muscular dystrophy and adrenal hypoplasia congenita. Isolated glycerol kinase deficiency has an inconstant phenotype, ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation. Although intragenic mutations were reported recently, the pathophysiological basis for the phenotypic variability remains unknown. To understand better the physiological significance of glycerol kinase and the pathophysiology of its deficiency, we generated glycerol kinase-deficient mice by gene targeting. Mutant male mice appear normal at birth, but exhibit postnatal growth retardation, altered fat metabolism with profound hyperglycerolemia and elevated free fatty acids, autonomous glucocorticoid synthesis and death by 3-4 days of age. Heterozygous females are healthy and biochemically normal. The biochemical features observed in glycerol kinase-deficient mice provide the basis for further investigations into the pathogenesis of the human disorder.
Hum Mol Genet 1997 Oct
PMID:X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death. 930 56

Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with metabolic and neurological crises. Liver shows the highest level of glycerol kinase (GK) activity in humans and mice. Absence of genotype-phenotype correlations in patients with GKD indicates the involvement of modifier genes, including other network partners. To understand the molecular pathogenesis of GKD, we performed microarray analysis on liver mRNA from neonatal glycerol kinase (Gyk) knockout (KO) and wild-type (WT) mice. Unsupervised learning revealed that the overall gene expression profile of the KO mice was different from that of WT. Real-time PCR confirmed the differences for selected genes. Functional gene enrichment analysis was used to find 56 increased and 37 decreased gene functional categories. PathwayAssist analysis identified changes in gene expression levels of genes involved in organic acid metabolism indicating that GK was part of the same metabolic network which correlates well with the patients with GKD having metabolic acidemia during their episodic crises. Network component analysis (NCA) showed that transcription factors sterol regulatory element-binding protein (SREBP)-1c, carbohydrate response element-binding protein (ChREBP), hepatocyte nuclear factor-4 alpha (HNF-4alpha) and peroxisome proliferative-activated receptor-alpha (PPARalpha) had increased activity in the Gyk KO mice compared with WT mice, whereas SREBP-2 was less active in the Gyk KO mice. These studies show that Gyk deletion causes alterations in expression of genes in several regulatory networks and is the first time NCA has been used to expand on microarray data from a mouse KO model of a human disease.
Hum Mol Genet 2006 Feb 01
PMID:Targeted disruption of glycerol kinase gene in mice: expression analysis in liver shows alterations in network partners related to glycerol kinase activity. 1636 6

Glycerol is one of the essential nutrients in the mammalian body. Glycerol released from adipocytes is delivered to the liver and used for gluconeogenesis. The molecular mechanism of glycerol transport across the cell membrane remains unclear. AQPadipose, which we identified in human adipose cDNA project and later found to be human AQP7, is expressed in adipose tissue, and upregulated during fasting. AQP7 belongs to the aquaglyceroporin subfamily to permealize glycerol as well as water. Loss of function mutation of AQP7 in human caused disturbance of normal rise of plasma glycerol. Disruption of AQP7 gene in mice resulted in profound hypoglycemia during prolonged fasting because of impaired glycerol supply to the liver. In obesity, AQP7 is overexpressed in visceral fat,accompanied by portal hyperglycerolemia and systemic hyperglycemia. Considered together, these works indicate that AQP7 functions as a glycerol gateway molecule in adipocytes.
Cell Mol Biol (Noisy-le-grand) 2006 Oct 30
PMID:Impact of glycerol gateway molecule in adipocytes. 1754 20

Glycerol kinase has several diverse activities in mammalian cells. Glycerol kinase deficiency is a complex, single-gene, inborn error of metabolism wherein no genotype-phenotype correlation has been established. Since glycerol kinase has been suggested to exhibit additional activities than glycerol phosphorylation, expression level perturbation in this enzyme may affect cellular physiology globally. To investigate this possibility, we conducted metabolic investigations of wild-type and two glycerol kinase-overexpressing H4IIE rat hepatoma cell lines constructed in this study. The glycerol kinase-overexpressing cell lines exhibited a significantly higher consumption of carbon sources per cell, suggesting excess carbon expenditure. Furthermore, we quantified intracellular metabolic fluxes by employing stable isotope 13C labeling with a mathematically designed substrate mixture, gas chromatography-mass spectrometry, and comprehensive isotopomer balancing. This flux analysis revealed that the pentose phosphate pathway flux in the glycerol kinase-overexpressing cell lines was 2-fold higher than that in the wild-type, in addition to subtler flux changes in other pathways of carbohydrate metabolism. Furthermore, the activity and transcript level of the lipogenic enzyme glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway, were also about 2-fold higher than that of the wild-type; these data corroborate the flux analysis results. This study shows that glycerol kinase affects carbon metabolism globally, possibly through its additional functions, and highlights glycerol kinase's multifaceted role in cellular physiology.
Mol Genet Metab 2008 Feb
PMID:Global metabolic effects of glycerol kinase overexpression in rat hepatoma cells. 1802 14

Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism at the interface of fat and carbohydrate metabolism. We report a male patient with GKD and a novel insertion of TT in exon 5 at position 378 of the GK cDNA (378-379insTT). This resulted in a premature stop codon and 0.8% normal GK activity. The mother is a carrier for this mutation and had gestational diabetes requiring insulin during this pregnancy but not in her previous pregnancy. Given the association between GKD and type 2 diabetes mellitus, it is interesting that the mother had gestational diabetes while carrying an affected fetus. Therefore, GKD is another disease where there may be a maternal-fetal interaction based on genotype. Further investigations may help elucidate the role of GKD in the carrier mother's gestational diabetes. In addition, these studies will provide better-informed counseling to families with GKD regarding the risk to carrier females.
Mol Genet Metab Rep 2015 Sep 01
PMID:Gestational Diabetes Associated with a Novel Mutation (378-379insTT) in the Glycerol Kinase Gene. 2630 14