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. Author manuscript; available in PMC: 2021 Aug 14.
Published in final edited form as: ACS Infect Dis. 2020 Jul 27;6(8):2214–2224. doi: 10.1021/acsinfecdis.0c00329

Figure 4. Succinylation provides an additional layer of metabolic regulation for cholesterol utilization in Mtb.

Figure 4.

During cholesterol catabolism in Mtb, the cellular NADH pool increases, and toxic propionyl-CoA is produced (blue box). Succinyl-CoA is produced by C and D ring metabolism and by carboxylation of propionyl-CoA to form methylmalonyl-CoA followed by isomerization (purple box). The cholesterol catabolic enzyme EchA19 is post-translationally regulated by succinylation, which reduces the enzyme’s activity, suggesting that a negative feedback mechanism regulates cholesterol catabolism on the basis of the levels of propionyl-CoA and succinyl-CoA produced (gray box). Succinylation of EchA19 is reversed by Rv1151c. Several other enzymes at each stage of cholesterol catabolism have known sites of succinylation,25 and the catalytic activities of these enzymes are postulated to be similarly regulated by this modification. HIP: 3aα‐H‐4α(3’‐propanoate)‐7aβ‐methylhexahydro‐1,5‐indanedione.