FIGURE 1 | Overview of metabolism.

From the following article:

The engine driving the ship: metabolic steering of cell proliferation and death

Marisa R. Buchakjian & Sally Kornbluth

Nature Reviews Molecular Cell Biology 11, 715-727 (October 2010)


The engine driving the ship: metabolic steering of cell proliferation and death

Metabolic pathways important to this Review include glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway (PPP) and fatty acid biosynthesis. Glucose enters the cell and is phosphorylated to glucose-6-phosphate (G6P) by hexokinase (1). G6P either proceeds through glycolysis to produce ATP, NADH and pyruvate (2), or through the PPP, producing ribose-5-phosphate and NADPH (3). G6P dehydrogenase (G6PD) dictates entry of G6P into the PPP, and G6P oxidation produces NADPH. NADPH is an important cellular antioxidant and is a cofactor in the reductive biosynthesis of fatty acids, nucleotides and amino acids. Pyruvate produced by glycolysis is converted to acetyl-CoA, which enters the TCA cycle and produces two ATP molecules and six NADH molecules per glucose (4). NADH is then used in mitochondrial oxidative phosphorylation for ATP production. Glutamine and other amino acids also feed into the TCA cycle; glutamine, for example, is converted to glutamate by glutaminase, and glutamate can be converted to α-ketoglutarate (5). Acetyl-CoA is also an important precursor for fatty acid biosynthesis. Intramitochondrial acetyl-CoA and oxaloacetate combine to form citrate, which is transported out of the mitochondria and broken back down by ATP citrate lyase (ACL) (6). Acetyl-CoA can be used as a precursor for post-translational acetylation of proteins and can also be converted to malonyl-CoA by acetyl-CoA carboxylase (ACC), resulting in the synthesis and elongation of fatty acid chains (7). GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GLUT, glucose transporter; F6P, fructose-6-phosphate; FAS, fatty acid synthase; PDH, pyruvate dehydrogenase; PEP, phosphoenolpyruvate; PFK1, phosphofructokinase 1; PFKFB, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase; PGI, phosphoglucose isomerase; PK, pyruvate kinase.

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