Phosphohexose isomerase (PHI; D-glucose-6-phosphate ketol-isomerase; EC 5.3.1.9 ) is also known as glucosephosphate isomerase (GPI) and phosphoglucose isomerase (PGI). It catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, the second step of the Embden-Meyerhof glycolytic pathway.
NCBI Summary:
This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts glucose-6-phophsate and fructose-6-phosphate. Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
General function
Ligand, Enzyme, Isomerase
Comment
Cellular localization
Secreted, Cytoplasmic
Comment
Ovarian function
Oogenesis
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte, Luteal cells
Comment
Expression and secretion of glucose-6-phosphate-isomerase by the ferret (Mustela putorius) corpus luteum.(Schulz LC, Van Cleeff J, Bahr JM. in BIOLOGY OF REPRODUCTION v. 66(S1) pp. 256-256 2002 Abstract)
Follicle stages
ovarian tumor
Comment
To define the molecular changes associated with ovarian cancer, DNA microarray analysis has been adapted to detect differentially expressed genes in human normal ovary tissue, borderline, and invasive epithelial ovarian tumors. The differential expression of genes in the tumor tissues and normal tissues was confirmed by Northern and/or semi-quantitative RT-PCR analysis. Analysis of the differential gene-expression profiles of the normal and neoplastic ovary allowed us to detect previously unidentified genes in ovarian tissues. Lee BC, et al observed up-regulation of the following genes in ovarian cancer: catechol-O-methyltransferase (COMT), the autocrine motility factor neuroleukin (NLK), the transcription regulator high mobility group I proteins (HMGI), the tyrosine kinase receptor ErbB-3, S100-alpha protein and Acyl-CoA-binding protein (ACBP). The transcription factor, chicken ovalbumin up-stream promoter transcription factor II (COUP-TFII), was the only gene down-regulated in ovarian cancer. Comparable gene-expression profiles were previously reported in breast cancer, suggesting that similar molecular events also exist in ovarian cancer. Our microarray analysis showed that most differentially expressed genes in ovarian cancer are linked to glucose/insulin metabolism, providing a possible molecular link between the glucose/insulin signaling pathway and the neoplasms of ovarian cancer.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment:Kelly et al reported the survival and normal function of glycolysis-deficient mouse
oocytes.
Mouse embryos homozygous for a null allele of Gpi1 which encodes the
glycolytic enzyme glucose phosphate isomerase fail to complete gastrulation
and die at about embryonic day 7.5, but mutant cells can survive in fetal
chimaeras in which they are mixed with wild-type cells. An adult female mouse
chimaera, composed of wild-type cells and homozygous Gpi1(-/-) null mutant
cells, was produced to test whether the presence of wild-type cells in the
ovary allowed mutant oocytes to survive and function. This mouse produced 28
offspring, eight of which were derived from homozygous Gpi1(-/-) null oocytes.
DNA in situ hybridization also showed that some Gpi1(-/-) follicle cells were
able to survive in chimaeric ovarian follicles. It is likely that the survival
of mutant follicle cells and fully functional mutant oocytes was mediated by
the presence of wild-type cells that could provide metabolic intermediates and
so bypass the block in the glycolytic pathway. Wild-type cumulus cells
probably supported the growing GPI-deficient oocytes via metabolic
co-operation, by passing ATP and other glycolytic products through gap
junctions. It was concluded that female mouse germ cells and ovarian follicle
cells do not need an intact endogenous glycolytic pathway if they can obtain
appropriate metabolites from an exogenous source.