Molecular and Cellular Biochemistry

, Volume 45, Issue 3, pp 137–149 | Cite as

The mitochondrial glycine cleavage system

Unique features of the glycine decarboxylation
  • G. Kikuchi
  • K. Hiraga


The glycine cleavage enzyme system is composed of four different proteins tentatively called P-protein, H-protein, T-protein and L-protein, and catalyzes the following reaction reversibly: Glycine + tetrahydrofolate + NAD+ ⇋ 5, 10-methylene-tetrahydrofolate + NH3 + CO2 + NADH + H

Glycine decarboxylase, tentatively called P-protein, is able by itself to catalyze glycine decarboxylation, yielding methylamine as product, but at an extremely low rate. P-Protein alone is also able to catalyze slightly the exchange of carboxyl carbon of glycine with CO2. However, the rates of the P-protein-catalyzed reactions are greatly increased by the co-existence of aminomethyl carrier protein, a lipoic acid-containing enzyme tentatively called H-protein. Several lines of evidence suggest that H-protein brings about a conformational change of P-protein which may be relevant to the expression of the decarboxylase activity of P-protein and that the functional glycine decarboxylase may be an enzyme complex composed of both P-protein and H-protein. H-Protein seems to play a dual role in the glycine decarboxylation; the one as a regulatory protein of P-protein, and the other as an electron-pulling agent and concomitantly as a carrier of the aminomethyl moiety derived from glycine. The idea that H-protein functions as a modulator of P-protein was further supported by the study of a patient with nonketotic hyperglycinemia. The primary lesion in this patient appeared to consist in structural abnormality in H-protein; the H-protein purified from the liver of this patient was apparently devoid of functional lipoic acid. Nevertheless, H-protein from the patient could stimulate the P-protein-catalyzed exchange of the carboxyl carbon of glycine and CO2, although only to a limited extent. The observed activity should be independent of the functioning of lipoic acid and would be a reflection of a conformational change in P-protein brought about by H-protein.

P-Protein was inactivated when it was incubated with glycine in the presence of II-protein, and the inactivation was completely prevented when bicarbonate was further added so as to allow the glycine-CO2 exchange to proceed. The inactivation was accompanied by a spectral change of P-protein. The inactivation of P-protein seemed to take place as a side reaction of the glycine decarboxylation and to reflect the formation of a ternary complex of P-protein, H-protein and aminomethyl moiety of glycine through a Schiff base linkage of the H-protein-bound aminomethyl moiety with the pyridoxal phosphate of P-protein.


Glycine Schiff Base Lipoic Acid Methylamine Aminomethyl 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Martinus Nijhoff/Dr W. Junk Publishers 1982

Authors and Affiliations

  • G. Kikuchi
    • 1
  • K. Hiraga
    • 1
  1. 1.Dept. of BiochemistryTohoku University School of MedicineSendaiJapan

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