|Gene:||GLDC||Accession Number: G-9891 (MetaCyc)|
Species: Gallus gallus
Component of: glycine cleavage complex (extended summary available)
The relative molecular mass of native glycine decarboxylase purified from Gallus gallus (chicken) liver was determined to be approximately 200 kD by sedimentation equilibrium, gel filtration, and sucrose density gradient centrifugation [Hiraga80a].
Glycine decarboxylase, also referred to as P-protein, or glycine dehydrogenase (decarboxylating), is a pyridoxal phosphate enzyme. It catalyzes the initial reaction of the glycine cleavage complex as shown in MetaCyc pathway glycine cleavage. A crystal structure for P-protein from the bacterium Thermus thermophilus HB8 has been determined [Nakai05].
In humans, mutations in gene GLDC (GCSP) that encodes P-protein can result in nonketotic hyperglycinemia. This inborn error of metabolism results in accumulation of large amounts of glycine in body fluids, causing neurological symptoms [Sellner05, Kure06].
The relative molecular mass of the glycine decarboxylase subunit purified from Gallus gallus (chicken) liver was determined by SDS-PAGE [Hiraga80a].
Gene Citations: [Kume91]
|Map Position: [28,557,831 <- 28,588,002]|
Molecular Weight of Polypeptide: 111.85 kD (from nucleotide sequence), 100 kD (experimental) [Hiraga80a ]
Molecular Weight of Multimer: 200 kD (experimental) [Hiraga80a]
pI: 7.2 [Hiraga80a]
Relationship Links: InterPro:IN-FAMILY:IPR001597 , InterPro:IN-FAMILY:IPR003437 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015424 , InterPro:IN-FAMILY:IPR020580 , InterPro:IN-FAMILY:IPR020581 , Panther:IN-FAMILY:PTHR11773 , Pfam:IN-FAMILY:PF01212 , Pfam:IN-FAMILY:PF02347
|Cellular Component:||GO:0005739 - mitochondrion [Hiraga80a]|
Enzymatic reaction of: glycine decarboxylase
Synonyms: glycine dehydrogenase (decarboxylating), P-protein
EC Number: 188.8.131.52
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
This reaction is reversible.
Glycine decarboxylase catalyzes the decarboxylation of glycine and the transfer of the methylamine group of glycine to a sulfur atom on the lipoamide moiety of H-protein. This produces the aminomethyl intermediate attached to the lipoate cofactor of H-protein [OkamuraIkeda05, Faure00].
Glycine decarboxylase enzyme preparations were assayed for P-protein, or H-protein activities by measuring the amount of [14C]bicarbonate incorporated into the carboxyl carbon of glycine during the exchange reaction, using purified H-protein for P-protein assay, or purified P-protein for H-protein assay [Hiraga80a].
Glycine decarboxylase activity was assayed by measuring glycine decarboxylation catalyzed by P-protein alone. In this assay, P-protein catalyzed the production of 14CO2 and methylamine from [1-14C]glycine. The pH optimum was 6.0 and methylamine was a competitive inhibitor. P-protein alone was also shown to catalyze the exchange reaction between the glycine carboxyl carbon and carbon dioxide. Addition of lipoate stimulated both reactions [Hiraga80a].
pH(opt): 6 [Hiraga80a]
Subunit of: glycine cleavage complex
Synonyms: glycine cleavage system, glycine decarboxylase multienzyme system, glycine decarboxylase multienzyme complex, glycine synthase, GCV
Species: Gallus gallus
Subunit composition of
glycine cleavage complex = [(GLDC)2][AMT][H-protein-(lipoyl)lysine][DLD]
glycine decarboxylase = (GLDC)2 (summary available)
glycine decarboxylase subunit = GLDC
aminomethyltransferase = AMT (summary available)
lipoamide dehydrogenase = DLD (extended summary available)
The overall mechanism of the glycine cleavage reaction has been studied using purified glycine decarboxylase (P-protein), aminomethyltransferase (T-protein) and H-protein-(lipoyl)lysine (H-protein) from Gallus gallus (chicken) liver (for a pathway representation of the glycine cleavage reactions see MetaCyc pathway glycine cleavage). Glycine is decarboxylated by P-protein to yield carbon dioxide, and the remaining methylene carbon and amino group of glycine are transferred to a free sulfhydryl group on the lipoyl moiety of H-protein, forming an intermediate. T-protein catalyzes the degradation of this intermediate, in the presence of tetrahydrofolate, to 5,10-methylene tetrahydrofolate and ammonia [Fujiwara84]. H-protein is required to significantly catalyze these reactions, and the formation of relatively stable 1:1 complexes between each P-protein subunit and H-protein, and T-protein and H-protein, has been shown [Hiraga80, OkamuraIkeda82].
The subunit ratio in the chicken glycine cleavage complex has not been reported. However, the subunit ratio in the glycine cleavage complex of the pea plant (Pisum sativum) has been estimated to be 2 P-protein : 27 H-protein : 9 T-protein : 1 L-protein, although an intact complex has not been isolated (in [Faure00]). The glycine cleavage complex of rat liver has been localized to the inner mitochondrial membrane [Motokawa74].
The reactions of the glycine cleavage complex are reversible, and also provide a route for glycine biosynthesis (see MetaCyc pathway glycine biosynthesis II).
|Cellular Component:||GO:0005739 - mitochondrion [Hiraga72]|
Enzymatic reaction of: glycine cleavage complex
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.
This reaction is reversible.
All four components of the glycine cleavage complex partially purified from Gallus gallus (chicken) liver mitochondria were essential for the overall reactions of glycine biosynthesis, or glycine cleavage [Hiraga72].
Faure00: Faure M, Bourguignon J, Neuburger M, MacHerel D, Sieker L, Ober R, Kahn R, Cohen-Addad C, Douce R (2000). "Interaction between the lipoamide-containing H-protein and the lipoamide dehydrogenase (L-protein) of the glycine decarboxylase multienzyme system 2. Crystal structures of H- and L-proteins." Eur J Biochem 267(10);2890-8. PMID: 10806386
Fujiwara84: Fujiwara K, Okamura-Ikeda K, Motokawa Y (1984). "Mechanism of the glycine cleavage reaction. Further characterization of the intermediate attached to H-protein and of the reaction catalyzed by T-protein." J Biol Chem 259(17);10664-8. PMID: 6469978
Hiraga80: Hiraga K, Kikuchi G (1980). "The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein." J Biol Chem 255(24);11671-6. PMID: 7440563
Hiraga80a: Hiraga K, Kikuchi G (1980). "The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria." J Biol Chem 255(24);11664-70. PMID: 7440562
Kume91: Kume A, Koyata H, Sakakibara T, Ishiguro Y, Kure S, Hiraga K (1991). "The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures." J Biol Chem 266(5);3323-9. PMID: 1993704
Kure06: Kure S, Kato K, Dinopoulos A, Gail C, DeGrauw TJ, Christodoulou J, Bzduch V, Kalmanchey R, Fekete G, Trojovsky A, Plecko B, Breningstall G, Tohyama J, Aoki Y, Matsubara Y (2006). "Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia." Hum Mutat 27(4);343-52. PMID: 16450403
Maaheimo01: Maaheimo H, Fiaux J, Cakar ZP, Bailey JE, Sauer U, Szyperski T (2001). "Central carbon metabolism of Saccharomyces cerevisiae explored by biosynthetic fractional (13)C labeling of common amino acids." Eur J Biochem 268(8);2464-79. PMID: 11298766
Motokawa74: Motokawa Y, Kikuchi G (1974). "Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components." Arch Biochem Biophys 164(2);624-33. PMID: 4460882
Nakai05: Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N (2005). "Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia." EMBO J 24(8);1523-36. PMID: 15791207
OkamuraIkeda05: Okamura-Ikeda K, Hosaka H, Yoshimura M, Yamashita E, Toma S, Nakagawa A, Fujiwara K, Motokawa Y, Taniguchi H (2005). "Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia." J Mol Biol 351(5);1146-59. PMID: 16051266
OkamuraIkeda82: Okamura-Ikeda K, Fujiwara K, Motokawa Y (1982). "Purification and characterization of chicken liver T-protein, a component of the glycine cleavage system." J Biol Chem 257(1);135-9. PMID: 7053363
Pasternack92: Pasternack LB, Laude DA, Appling DR (1992). "13C NMR detection of folate-mediated serine and glycine synthesis in vivo in Saccharomyces cerevisiae." Biochemistry 31(37);8713-9. PMID: 1390656
Sellner05: Sellner L, Edkins E, Greed L, Lewis B (2005). "Detection of mutations in the glycine decarboxylase gene in patients with nonketotic hyperglycinaemia." Mol Genet Metab 84(2);167-71. PMID: 15670722
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