Glyceraldehyde 3-phosphate

In addition to this long established metabolic function, GAPDH has recently been implicated in glyceraldehyde 3-phosphate non-metabolic processes, including transcription activation, initiation of apoptosis[4] ER-to-Golgi vesicle shuttlingand fast axonal, or axoplasmic transport.

Any bacterial metabolite produced during a metabolic reaction in Escherichia coli. Any mammalian metabolite produced during a metabolic reaction in humans Homo sapiens. Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms. Read more News Our impact Contact us Intranet. Privacy Notice and Terms of Use.

Glyceraldehyde 3-phosphate

Federal government websites often end in. The site is secure. Glyceraldehydephosphate dehydrogenase GAPDH is a glycolytic enzyme whose role in cell metabolism and homeostasis is well defined, while its function in pathologic processes needs further elucidation. These interprotein interactions and post-translational modifications of GAPDH mediate its cytotoxic or cytoprotective functions in the manner of a Janus-like molecule. In this review, we discuss the functional features of the enzyme in cellular physiology and its possible involvement in human pathologies. Glyceraldehydephosphate dehydrogenase GAPDH is one of the major housekeeping proteins, comprising approximately 2,, molecules per cell and occurring in molar concentrations of about 0. With such a high content, the enzyme can reach its well-known functional diversity by interacting with miscellaneous protein partners as well as with DNA and RNA species [ 2 ]. GAPDH is a homo-tetramer and one of the cellular proteins abnormally enriched by reactive sulfhydryl groups; this explains the unusually high aggregation capacity of the S -nitrosylated or oxidized protein. Importantly, these modifications have a significant impact on a great variety of neurodegenerative processes [ 3 , 4 ]. The enzyme catalyzes the glycolytic reaction resulting in the creation of macroergic products and NADH, which are used further in reactions of oxidative phosphorylation [ 5 ]. In addition, the activities of GAPDH may be regulated by redox reactions, for example S -thiolation, which appears to serve an adaptive function during exposure to an oxidative stress [ 6 ]. GAPDH is capable of functioning in the cell both in the enzymatically active, tetrameric form necessary for glycolysis, and in the dimeric or monomeric forms [ 7 , 8 ]. Moreover, the cellular localization of GAPDH is not limited to the cytoplasm, the protein is found in the nucleus and other intracellular organelles [ 9 ], including plasma membrane [ 10 ]. Additionally, a distinct, sperm-specific form of GAPDH is isolated, the main function of which is glycolysis, and impaired functioning may cause male infertility [ 17 ]. One of the features for which GAPDH is known around the world is its use as a loading control in hundreds of studies dedicated to the analysis of omics.

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Glyceraldehydephosphate dehydrogenase GAPDH is a highly conserved enzyme within the glycolytic pathway. Two copies of genes encoding GAPDH were characterized, then endogenously overexpressed and silenced through Agrobacterium tumefaciens -mediated transformation methods. Analysis of metabolite and enzyme expression levels revealed that the increased lipid content of MA-GAPDH1 was due to enhanced flux of glyceraldehydephosphate to glycerate-1, 3-biphosphate. Mortierella alpina is an oleaginous filamentous fungus with a strong ability to accumulate polyunsaturated fatty acids PUFAs and has been used in industrial production of arachidonic acids ARA Tsunehiro et al. Great efforts have been made to improve its lipid yield, production and productivity Koike et al.

In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis , [4] ER-to-Golgi vesicle shuttling , and fast axonal, or axoplasmic transport. This form is composed of four identical kDa subunits containing a single catalytic thiol group each and critical to the enzyme's catalytic function. GAPDH is encoded by a single gene that produces a single mRNA transcript with 8 splice variants, though an isoform does exist as a separate gene that is expressed only in spermatozoa. Enzyme 1. GAPDH uses covalent catalysis and general base catalysis to decrease the very large activation energy of the second step phosphorylation of this reaction. First, a cysteine residue in the active site of GAPDH attacks the carbonyl group of G3P, creating a hemithioacetal intermediate covalent catalysis. The hemithioacetal is deprotonated by a histidine residue in the enzyme's active site general base catalysis. Deprotonation encourages the reformation of the carbonyl group in the subsequent thioester intermediate and ejection of a hydride ion. This thioester species is much higher in energy less stable than the carboxylic acid species that would result if G3P were oxidized in the absence of GAPDH the carboxylic acid species is so low in energy that the energy barrier for the second step of the reaction phosphorylation would be too high, and the reaction, therefore, too slow and unfavorable for a living organism.

Glyceraldehyde 3-phosphate

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According to the recent data, the PTP opening may be caused by the denatured GAPDH as a result of S-nitrosylation of C residue; the replacement of C with alanine resulted in the blockage of cell death in response to nitrosative stress [ 59 ], which proves the importance of GAPDH nitrosylation in regard to the advancement of apoptosis. Liang S. This finding supplements a new member of the NADPH suppliers for lipid biosynthesis and helps elucidate the lipid biosynthesis mechanisms in oleaginous microorganism. Monoisotopic Mass. Neural Transm. Further studies are needed to demonstrate the advantages of the above approaches to suppress the pathogenic effects of modified and aggregating GAPDH. Biochemical and Biophysical Research Communications. Chang C. Song S. National Center for Biotechnology Information, U. The 18S rRNA gene was used as internal gene control. CiteSeerX GAPDH is overexpressed in multiple human cancers, such as cutaneous melanoma , and its expression is positively correlated with tumor progression. Using the chromatin immunoprecipitation assay on colon cancer cells, it was proved that GAPDH directly interacts with the SP1 transcription factor, which leads to an increased expression of zinc finger protein SNAI1 Snail , the master regulator of the epithelial—mesenchymal transition [ 21 , 46 , ].

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During plant photosynthesis , 2 equivalents of glycerate 3-phosphate GP; also known as 3-phosphoglycerate are produced by the first step of the light-independent reactions when ribulose 1,5-bisphosphate RuBP and carbon dioxide are catalysed by the rubisco enzyme. Tian X. Supplier Information. Chemical modifications and denaturation of GAPDH can slow down the glycolytic cycle and disrupt the cellular metabolism [ 81 ]. Drug Resist. B is the NADH amount from standard curve nmol. In the aspect of oncological diseases, it is obvious that there is an acute issue of targeted delivery of GAPDH glycolytic activity inhibitors, for example, using liposomes. Article Talk. Introduction Glyceraldehydephosphate dehydrogenase GAPDH is one of the major housekeeping proteins, comprising approximately 2,, molecules per cell and occurring in molar concentrations of about 0. Sen T. Finally, the data obtained on human aortic smooth muscle cells shows that the down-regulation of GAPDH glycolytic activity and subsequent ATP depletion caused alterations in arterial wall energy homeostasis leading to atherosclerotic pathogenesis [ 85 ]. Pyruvate synthase. The enhancement of glycolysis regulates pancreatic cancer metastasis. Secondary damage after ischemic renal injury. ISBN