Citrate shuttle

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The citrate shuttle (also citrate-malate shuttle or citrate-malate-pyruvate cycle ) is a transport mechanism for the salt of citric acid across the inner mitochondrial membrane . In the process, an acetyl residue is transferred to oxaloacetate. The resulting citrate represents the actual form of transport. The citrate shuttle plays an important role in anabolic metabolic processes such as fatty acid synthesis and is an alternative source for the supply of NADPH .

The transport mechanism was postulated in 1965 by Melodee S. Kornacker and Eric G. Ball after experiments on rats , which is why it is occasionally referred to as the Ball cycle .

Basics

Acetyl-CoA (“activated acetic acid”) is the usual form that acetic acid is in the body. It is used for numerous biochemical processes in the cytosol , e.g. B. in fatty acid synthesis required, but arises - z. B. in the course of β-oxidation - mainly in the matrix of the mitochondrion. However, the inner mitochondrial membrane is impermeable to acetyl-CoA so that it cannot diffuse through the membrane. In addition, in contrast to long-chain fatty acids , acetate can not be transported using carnitine . This results in the need for a separate transport mechanism for acetate.

mechanism

Scheme of the mechanism of the citrate shuttle. A : citrate carrier (tricarboxylate carrier ), B : pyruvate / H + symporter

In the matrix, oxaloacetate and acetyl-CoA are first condensed to citrate by the enzyme citrate synthase . The citrate formed is transported out of the mitochondrial matrix by an antiporter , the tricarboxylate carrier ( A , see illustration), with one molecule of malate per molecule of citrate entering the matrix. On the cytosolic side, the enzyme ATP citrate lyase splits citrate again into oxaloacetate and acetyl-CoA using ATP . The oxaloacetate is then reduced to malate by the enzyme malate dehydrogenase and NADH . The malate formed can now pass directly through the antiporter back into the mitochondrion, where it is oxidized to oxaloacetate and the cycle closes. Alternatively, the malate to be pyruvate by an NADP-dependent malic enzyme oxidatively decarboxylated , a pyruvate / H + - symporter ( B transported) in the matrix and there - carboxylated to oxaloacetate again - with the consumption of one molecule ATP. This also closes the cycle.

In the first way (direct transport of the malate) one molecule of ATP is used for the transport of an acetate molecule, in the second way (return transport via pyruvate) it is two ATP and in addition one molecule of NADP + is reduced to one molecule of NADPH. In addition to the pentose phosphate pathway and the citrate cycle (conversion of isocitrate to oxalic succinate), this is the only way to generate NADPH.

Individual evidence

  1. ↑ Kornacker, MS. and Ball, EG. (1965): Citrate cleavage in adipose tissue . In: Proc Natl Acad Sci USA . Volume 54, Number 3, September 1965, pp. 899-904, PMID 4379378 , PMC 219762 (free full text).
  2. ^ David Nelson, Michael Cox: Lehninger Biochemie . Springer, Berlin; 4th, completely revised u. exp. Edition 2009; ISBN 978-3-540-68637-8 ; P. 1076.

literature

  • Werner Müller-Esterl et al .: Biochemistry, an introduction for physicians and natural scientists. Spectrum Academic Publishing House, 2004, ISBN 3827405343