My Cancer Genome: Genetically Informed Cancer Medicine

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Metabolic Signaling

Metabolic pathways promote the chemical reactions of anaerobic and aerobic respiration to generate cellular energy through the breakdown of sugars. The lactic acid cycle (anaerobic) generates ATP in the absence of oxygen and the TCA cycle (aerobic) generates ATP in the presence of oxygen. In humans, the TCA cycle occurs in cellular mitochondria and is the metabolic pathway that controls carbohydrate, fat, and protein metabolism. Ultimately, these chemical processes generate cellular energy to carry out processes such as cell growth, proliferation, differentiation, and survival.

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Figure 1. Glycolysis breaks down glucose into two pyruvate molecules. In the absence of oxygen, pyruvate enters the lactic acid cycle and, via lactate dehydrogenase, produces lactic acid and 2 molecules of ATP. In the presence of oxygen, pyruvate is imported into the mitochondria and converted into acetyl-CoA. Acetyl-CoA enters the citric acid cycle (inset Box A) in order to produce the coenzymes NADH and FADH2. These coenzymes act as electron carriers to bring electrons to the electron transport chain (ETC; inset Box B), where they are used to drive the transport of protons across the inner mitochondrial membrane to generate a strong proton gradient. The influx of protons along the gradient is utilized by the ATP synthase to drive the generation of ATP by oxidative phosphorylation. The entrance of the two pyruvate molecules into the citric acid cycle and the ETC allows the generation of 32 molecules of ATP per initial glucose molecule. These metabolic processes are important for cellular metabolic regulation and contribute to healthy functioning by promoting processes such as cell growth, proliferation, differentiation, and survival. Click here to open a larger version of this image in a new window.

Diseases in Which Pathway is Aberrantly Activated

  • Acute myeloid leukemia
  • Glioma

Therapies That Target This Pathway

  • IDH1 inhibitors

Genes Involved in the Pathway

  • ACO1
  • ACO2
  • CS
  • FH
  • IDH1
  • IDH2
  • LDHA
  • LDHB
  • MDH2
  • OGDH
  • PC
  • PDHA1
  • PDHB
  • PKM
  • SUCLA2
  • SUCLG1
  • SUCLG2

Last Updated: May 24, 2016

Disclaimer: The information presented at MyCancerGenome.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.

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