AI Article Synopsis
- The mitochondrial malate dehydrogenase-citrate synthase (MDH-CS) multi-enzyme complex is crucial for the Krebs cycle, enabling efficient enzymatic reactions without losing intermediates.
- The study found that substrates like NAD and acetyl-CoA promote the formation of this complex, whereas products like NADH and citrate weaken it.
- Additionally, factors such as oxaloacetate (only with acetyl-CoA), ATP, and low pH contribute to the stability and interaction of the MDH-CS complex, indicating its role in regulating the Krebs cycle based on metabolic needs.
Article Abstract
Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle 'metabolon' which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was present together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455617 | PMC |
| http://dx.doi.org/10.1038/s41598-021-98314-z | DOI Listing |
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