BioMed Research International / 2018 / Article / Fig 2

Review Article

Cystathionine β-Synthase in Physiology and Cancer

Figure 2

Potential mechanisms underlying CBS deregulation with alterations of homocysteine and H2S levels in cancer pathogenesis. CBS deficiency causes hyperhomocysteinemia. Elevated Hcy concentration can increase reactive oxygen species (ROS) production and induce oxidative stress. Hyperhomocysteinemia also leads to formation of homocysteine thiolactone as a result of error-prone editing by the methionyl-tRNA synthase. This homocysteine derivative can cause protein N-homocysteinylation that impairs protein function, resulting in an unfolded protein response and endoplasmic reticulum (ER) stress. The elevated Hcy level can lead to accumulation of S-adenosyl homocysteine (SAH), a competitive inhibitor of most methyltransferases, consequently inducing DNA hypomethylation and affecting gene transcription. CBS-driven endogenous H2S production maintains mitochondrial respiration and ATP synthesis, promotes antioxidant production by enhancing Nrf2 activation and increasing glutathione production, and modulates protein activity via protein sulfhydration. Secreted H2S can cause vasodilation via activation of ATP-sensitive K+ channels.

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