Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.

Dirk Roosterman,Graeme Stuart Cottrell

doi:10.3390/ijms22020604

Abstract

In 1937, Sir H. A Krebs first published the Citric Acid Cycle, a unidirectional cycle with carboxylic acids. The original concept of the Citric Acid Cycle from Krebs’ 1953 Nobel Prize lecture illustrates the unidirectional degradation of lactic acid to water, carbon dioxide and hydrogen. Here, we add the heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex, connecting the original Citric Acid Cycle to the flow of energy and material. The heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex catalyses the first reaction of the Citric Acid Cycle, the oxidation of lactate to pyruvate, and thus secures the provision of pyruvic acid. In addition, we modify Krebs’ original concept by feeding the cycle with oxaloacetic acid. Our concept enables the integration of anabolic processes and allows adaption of the organism to recover ATP faster.

Highlights

Connecting Pyruvate Carboxylase “All science is either physics or stamp collecting” [1]
Enzymes of the glycolytic pathway can be aligned by year of discovery or, more classically, they can be didactically aligned based on the gradual degradation of the carbon backbone of glucose
The concept of proton transport chains (PTCs) was deduced from the substratechannelling hypothesis, which was experimentally demonstrated by Srivastava and Bernhard [14,15,16]

Summary

Introduction

Connecting Pyruvate Carboxylase “All science is either physics or stamp collecting” [1]. In the case of biochemistry, an enzyme, to the reaction does not change the equilibration between substrate and product but accelerates the process Our sorting of metabolic enzymes is in line with the ‘spirit’ of the Glansdorff–Prigogine principle, which is based on the notions of entropy production and energy dissipation. This means that entropy must be emitted to produce entropy. A water-free transfer of the substrate mathematically would provide an infinite concentration of the substrate and an infinite concentration would drive a coupled enzymatic reaction unidirectionally In this scenario, it is likely that CAII would position the active proton of H2 CO3 for the transfer to protonlinked MCT1. We postulate that LDH-h recovers activity by a NADH-H+ /NAD+ exchange with electron transport chain (ETC), and this exchange acts as a feedback mechanism

The Proton Transport Chain Hypothesis

Proton Transport

Proton Transport Chains and Citric Acid Cycles

Discussion