Glycolysis

Glycolysis is the metabolic process by which glucose is converted to pyruvate in a sequence of enzymatic steps. Hexokinase catalyzes the conversion of glucose to glucose-6-phosphate, the first step in glycolysis. Hexokinases I, II, and III are associated with the outer mitochondrial membrane and are critical for maintaining an elevated rate of aerobic glycolysis in cancer cells (Warburg effect).

Phosphofructokinase (PFK) catalyzes the phosphorylation of fructose-6-phosphate. Platelet-type phosphofructokinase (PFKP) is expressed in various cell types. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the phosphorylation of glyceraldehyde-3-phosphate.

Pyruvate kinase, a glycolytic enzyme, catalyses the conversion of phosphoenolpyruvate to pyruvate. In mammals, the M1 isoform (PKM1) is expressed in most adult tissues. The M2 isoform (PKM2), an alternatively-spliced variant of M1, is expressed during embryonic development.

Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and NADH to lactate and NAD+. LDHA expression is induced when the oxygen supply is too low for mitochondrial ATP production.

The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate and CoA into acetyl-CoA and CO₂ in the presence of NAD+. The reaction of oxidative decarboxylation of pyruvate serves as a critical link between glycolysis and the citric acid cycle and lipid metabolism.

Glycolysis Pathway Diagram

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References

• WARBURG O. On the origin of cancer cells. Science. 1956 Feb 24;123(3191):309-14. [PMID: 13298683].

• Barber RD, Harmer DW, Coleman RA, Clark BJ. GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics. 2005 May 11;21(3):389-95. [PMID: 15769908].

• Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem. 1996 Dec 20;271(51):32529-37. [PMID: 8955077].

Flora Flora is a technical support expert at EnkiLife, familiar with immunology and neuroscience, dedicated to providing customers with high-quality product combinations and technical support to help achieve research in neurodegenerative diseases and other neuroscience areas.