Disease relevance of GPD2

• To evaluate the significance of the mGPDH gene in the development of non-insulin-dependent diabetes mellitus (NIDDM), we set up primers and conditions for polymerase chain reaction (PCR) amplification of the coding exons and flanking regions [1].
• A selective deficiency of hGDH2 has been reported in patients with spinocerebellar ataxia [2].
• The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients [3].

High impact information on GPD2

• The gene frequencies of GDH1, GDH2, and GDH3 in these ethnic groups are significantly different from those reported in Caucasians [4].
• Mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is thought to be an important factor for glucose sensing in pancreatic beta cells [1].
• Linkage group 7 consists of sSOD-1 (cytosolic superoxide dismutase), GPD-2 (glycerol-3-phosphate dehydrogenase), mME (mitochondrial malic enzyme), and the sex determining locus [5].
• Study of structure-function relationships, using site-directed mutagenesis of GLUD1 at single sites differing from GLUD2, showed that the Arg443Ser and the Gly456Ala change reproduced some, but not all, of the properties of hGDH2 [6].
• Functional analyses of highly purified recombinant wild-type hGDH2 revealed that this adaptive evolution dissociated the enzyme from GTP control, permitted regulation almost entirely by ADP and/or L-leucine, and fine-tuned its activity to the relatively low cellular pH that occurs in synaptic astrocytes during excitatory transmission [6].

Chemical compound and disease context of GPD2

• The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mtGPD) plays an important role in the regulation of insulin secretion and has been postulated as a candidate responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in humans as well as in rodent models of NIDDM [7].

Biological context of GPD2

• Replacement of Ser by Arg at the 443 site by cassette mutagenesis abolished the heat lability of hGDH2 with a similar half-life of hGDH1 [2].
• SUBJECTS: Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients) [3].

Anatomical context of GPD2

• GP-dependent ferricyanide-induced peroxide production was also determined luminometrically, using mitochondria or partially purified mGPDH [8].
• In zoospores, PFK, FDP, and GDH2 were localized in the cytosol [9].
• Human GPDM either is not capable of being inserted into the rodent mitochondrial membrane or is regulated in some way in the hybrid cells by an unidentified rodent factor [10].

Associations of GPD2 with chemical compounds

• One-electron acceptor, potassium ferricyanide, highly stimulated the rate of GP-dependent antimycin A-insensitive oxygen uptake, which was prevented by inhibitors of mitochondrial GP dehydrogenase (mGPDH) or by coenzyme Q (CoQ) [8].
• These results indicate that hydrogen peroxide is produced directly by mGPDH and reflect the differences in the transport of reducing equivalents from mGPDH and succinate dehydrogenase to the CoQ pool [8].
• GDH2 varied similarly to PFK and IDHNADP during OC plant development, whereas it behaved like isocitrate lyase during RS plant development [9].
• The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mGPDH) is an essential component of the glycerol phosphate shuttle which transfers reduction equivalents from the cytoplasm into the mitochondria [11].
• In the present study, the cassette mutagenesis at several putative positions (K94, G96, K118, K130, or D172) was performed to examine the residues involved in the glutamate-binding of the human glutamate dehydrogenase isozymes (hGDH1 and hGDH2) [12].

Other interactions of GPD2

• Transcription of gpd1 could be detected during vegetative growth under both aerobic and anaerobic conditions, whereas neither gpd2 nor gpd3 transcription was detected, indicating that gpd1 is the major transcribed gpd gene [13].

Analytical, diagnostic and therapeutic context of GPD2

• Three genes (gpd1, gpd2, and gpd3) encoding glyceraldehyde-3-phosphate dehydrogenase were isolated from the dimorphic zygomycete Mucor circinelloides by PCR using degenerated primers [13].

References