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. 2022 Dec 26;299(2):102838. doi: 10.1016/j.jbc.2022.102838

Figure 2.

Figure 2

The reductive tricarboxylic acid (TCA) cycle. A simplified schematic depicting the reductive TCA cycle or reverse Krebs cycle. Most reactions of this cycle are the same as those of the oxidative TCA cycle but in reverse and are catalyzed by similar enzymes. The major exceptions include (1) cleavage of citrate to form oxaloacetate and acetyl-CoA and (2) the production of alpha-ketoglutarate (αKG) from succinyl-CoA. Citrate cleavage requires ATP and is carried out by ATP-citrate lyase (ACL) or the related citryl-CoA lyase and citryl-CoA synthase enzymes. Conversion of succinyl-CoA to αKG, mediated by αKG synthase, is highly energetically unfavorable and thus requires a strong reducing agent in the form of reduced ferredoxin (Ferredoxinred). While the oxidative TCA cycle combusts carbon and produces reducing equivalents that drive ATP synthesis, the reductive TCA cycle consumes ATP and reducing equivalents to assimilate carbon and produce acetyl-CoA. Reducing equivalents are shown in pink.