Glycolysis/TCA Cycle Molecular Checkpoint

Glycolysis Overview

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.

Metabolic Pathway Diagram

Glucose → GLUT → Plasma membrane → Cytoplasm → Glucose → Glucose-6-phosphate → Glycogen biosynthesis; 6-Phosphoglucono-δ-lactone → Nucleotide biosynthesis; Fructose-6-phosphate → Glucosamine-6-phosphate → Glucosamine biosynthesis; Fructose-1,6-bisphosphate → Glyceraldehyde-3-phosphate / Dihydroxyacetone phosphate → Glycerol-3-phosphate → Lipid biosynthesis; NADH → 1,3-Bisphosphoglycerate → ATP → 3-Phosphoglycerate → 3-Phosphohydroxypyruvate → Amino acid biosynthesis; 2-Phosphoglycerate → Phosphoenolpyruvate → ATP → Pyruvate → Lactate; NAD+ ↔ NADH.

Functions: Energy exchange, Allosteric regulation, Metabolic flux regulation, Regulation of intracellular protein homeostasis, Redox balance, NAD+-dependent deacetylation, ADP-ribosylation, Intracellular Ca²⁺ homeostasis, Immune responses, Genomic stability.

Relevant Antibodies

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