Disease relevance of GLDC

• Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation [1].
• INTERPRETATION: Prospective treatment with this regimen can favorably modify the early neonatal course of severe NKH but does not prevent the poor long-term outcome, suggesting glycine-induced prenatal injury and/or ongoing postnatal damage [1].
• Three unrelated adult patients with mild hyperglycinemia, infantile hypotonia, mental retardation, behavioral hyperirritability, and aggressive outbursts were screened for glycine decarboxylase (GLDC) mutations; two novel missense mutations (A389V and R739H) were found [2].
• Glycine decarboxylase activity, which might be involved in photorespiratory metabolism, has been found, however, in cell extracts of Anabaena sp. strain P.C.C. 7119 as the present study demonstrates [3].
• Apoptotic cell response in oats is induced by victorin, a host-selective toxin secreted by Cochliobolus victoriae and thought to exert toxicity by inhibiting mitochondrial glycine decarboxylase (GDC) in Pc-2/Vb oats [4].

High impact information on GLDC

• The pathogen-inducible nitric oxide synthase (iNOS) in plants is a variant of the P protein of the glycine decarboxylase complex [5].
• Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein [6].
• Previously, victorin was shown to be bound specifically by two proteins of the mitochondrial glycine decarboxylase complex, at least one of which binds victorin only in toxin-sensitive genotypes in vivo [7].
• Nucleotide sequence analysis of the cDNA revealed extensive homology to a previously cloned cDNA for the P protein component of the multienzyme complex glycine decarboxylase [8].
• Plant mitochondria possess all the necessary enzymatic equipment for de novo synthesis of tetrahydrofolate and lipoic acid, serving as cofactors for glycine decarboxylase and serine hydroxymethyltransferase functioning [9].

Chemical compound and disease context of GLDC

• Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia [10].
• A clinical strain of Escherichia coli (Ec GCE) displayed resistance to cefoxitin, cefotetan, cefotaxime, and ceftazidime [11].
• Isolation of an atypically small lipoamide dehydrogenase involved in the glycine decarboxylase complex from Eubacterium acidaminophilum [12].
• This study aimed to determine the association between the levels of granulocyte elastase and prostaglandin E2 (PGE2) in GCE and the concomitant presence of periodontopathogens in untreated adult periodontitis (AP) [13].

Biological context of GLDC

• Mutation analysis was performed by sequencing all GLDC, GCSH and AMT exons [1].
• A novel homozygous GLDC c.482A-->G(Y161C) missense mutation was identified [1].
• We have determined the structure of GLDC and of its pseudogene (psiGLDC) and studied their expression for a molecular analysis of NKH [14].
• Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms [15].
• The precursor glycine decarboxylase deduced from the 3514-base pair nucleotide sequence is comprised of 1,004 amino acids (Mr = 111,848) [16].

Anatomical context of GLDC

• METHODS: A newborn with NKH diagnosed prenatally following the neonatal death of a previous affected sibling was treated from birth with oral sodium benzoate (250 mg/kg/day) and the NMDA receptor antagonist ketamine (15 mg/kg/day) immediately after sampling cord blood and cerebrospinal fluid (CSF) for glycine determination [1].
• We conclude that, in pea leaf mitochondria, the pyruvate dehydrogenase and glycine decarboxylase complexes share the same dihydrolipoamide dehydrogenase [17].
• Purification and properties of glycine decarboxylase, a component of the glycine cleavage system, from rat liver mitochondria and immunochemical comparison of this enzyme from various sources [18].
• The incubation with P-gp monoclonal antibody and then the secondary alkaline phosphatase (AP) conjugated antibody introduced AP onto the K562/ADM cell immobilized on Au-CS/GCE [19].
• Structural and biochemical bases of photorespiration in C4 plants: quantification of organelles and glycine decarboxylase [20].

Associations of GLDC with chemical compounds

• Gene Symbol: GLDC. Disease: NKH glycine encephalopathy [21].
• A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem [22].
• The lipoamide arm in the glycine decarboxylase complex is not freely swinging [23].
• The mitochondrial glycine decarboxylase multienzyme system, connected to serine hydroxymethyltransferase through a soluble pool of tetrahydrofolate, consists of four different component enzymes, the P-, H-, T- and L-proteins [9].
• In the catalytic cycle of glycine decarboxylase, emphasis is given to the lipoate-dependent H-protein that plays a pivotal role, acting as a mobile substrate that commutes successively between the other three proteins [9].

Enzymatic interactions of GLDC

• Therefore, it was concluded that the loss of glycine decarboxylase activity was due to an inhibition of the reaction catalyzed by T-protein, which required ATP for its activation [24].

Other interactions of GLDC

• Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia [25].
• The first 30 amino acids of the N-terminal sequence of the mature E3 protein are identical with those of the mature L-protein of the glycine decarboxylase complex [17].
• The majority of cases are caused by mutations in the P-protein, one of the four components of the glycine cleavage enzyme, also known as glycine decarboxylase (GLDC) [26].
• Screening a DNA bank from 50 patients with enzymatic confirmation of their diagnosis of nonketotic hyperglycinemia gave allele frequencies of 5% for R515S of P-protein (glycine decarboxylase) and 7% for R320H of T-protein (aminomethyltransferase) [27].
• Progress has been made in the understanding of photorespiration and related proteins (Rubisco, glycolate oxidase and glycine decarboxylase) in the context of recent structural information [28].

Analytical, diagnostic and therapeutic context of GLDC

• GLDC expression in lymphoblasts was studied by Northern blot and reverse transcriptase PCR analysis [29].
• Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using psiGLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively [14].
• METHODS: The [1-(13)C]glycine breath test was performed in 10 control subjects and 5 glycine encephalopathy patients with GLDC mutation, including 1 patient with mild glycine encephalopathy [30].
• The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures [16].
• Prenatal diagnosis is possible by determining the activity of GCE and also by DNA analysis [31].

References