Coexistence of Defective Activity in Glycine-Cleavage Reaction and Propionly-CoA Carboxylase in the Liver of a Hyperglycinemic Child

Nishimura, Y.; Tada, Keiya; Arakawa, Tsuneo

doi:10.1620/tjem.113.267

Cited by 9 publications

(6 citation statements)

References 12 publications

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“…The coexistence of a defective activity of propionyl-CoA carboxylase (or MMA-CoA mutase, respectively) and of the glycine cleavage reaction to CO,, NH,, and a C , unit has been demonstrated both in vivo and in vitro in some other patients with propionic acidemia and methylmalonic acidemia (1,27,33). Keating et al (19) described recently a patient in whom a ketotic hyperglycinemia syndrome was associated with a defect in the isoleucine degradation pathway (presumably at the /I-ketothiolase site).…”

Section: Resultsmentioning

confidence: 99%

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Acute Neonatal Nonketotic Hyperglycinemia: Normal Propionate and Methylmalonate Metabolism

et al. 1975

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ExtractPropionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondria1 enzyme, and not by acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA.From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate-and M M A precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis. SpeculationThe metabolism of propionate, methylmalonate, and branched chain amino acids is normal in true nonketotic hyperglycinemia. Further investigations will have to show whether the observed block in the glycine cleavage reaction to CO,, NH,, and a single-carbon tetrahydrofolate derivative represents the primary enzymatic defect.

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Section: Resultsmentioning

confidence: 99%

“…glycinemia on the'basis of clinical ~y m p t o m s alone (24,27,34). In nonketotic hyperglycinemia a defective oxidation of C , of…”

Section: Speculationmentioning

confidence: 99%

Acute Neonatal Nonketotic Hyperglycinemia: Normal Propionate and Methylmalonate Metabolism

et al. 1975

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“…Similarly, if glucose is available, the heart does not use PCC, but it can be induced to do so if fat or propionate is added to the system [44]. Glycine cleavage is decreased leading to elevations in plasma glycine thus the historical name: ketotic hyperglycinemia for PA. PA individuals have decrease H protein of the glycine cleavage system, which is suspected to be due to propionyl-CoA accumulation [50, 51]. Glycine cleavage may also be impacted by accumulation of other similar intermediates including isobutryl-CoA and 2-oxo-isovaleryl-CoA [52].…”

Section: Reviewmentioning

confidence: 99%

Propionyl-CoA carboxylase – A review

Wongkittichote

Mew

Chapman

2017

Molecular Genetics and Metabolism

175

159

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Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual presenting with metabolic acidosis, hyperammonemia, lethargy, vomiting and sometimes coma and death if not treated. Individuals with propionic acidemia also have a number of long term complications resulting from the dysfunction of the PCC enzyme. Here we present an overview of the current knowledge about the structure and function of PCC. We review an updated list of human variants which are published and provide an overview of the disease.

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“…Using a more specific enzyme assay, Levin et al [12] found defective MMA-CoA mutase activity in leukocytes of two further patients. On the other hand, Nishimura et al [21] and Tada and Arakawa [29] reported normal pro pionate oxidation by leukocytes of their patient with propionic acidemia. Our somewhat unexpected findings and Tada's might be explained by either of the two following possibilities: the presence of isoenzymes in different tissues, i.e.…”

Section: Discussionmentioning

confidence: 85%

Congenital Methylmalonic Acidemia: a Variant of the B ‘Non-Responsive’ Form with Evidence for Reduced Affinity of Methylmalonyl-CoA Mutase for its B(12)-Coenzyme

Er¹,

Bachmann²,

Wick³

1976

Enzyme

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Methylmalonate metabolism was investigated in fibroblasts and leukocytes of two unrelated patients with a B(12)-nonresponsive type of congenital methylmalonic acidemia. Intact fibroblasts from both patients showed a defective metabolism of methyl^-14 C-malonate to 14C0(2), whereas no such defect was found in their intact peripheral leukocytes. In disrupted fibroblasts, the conversion of methylmalonyl coenzyme A to succinyl coenzyme A was markedly reduced but was completely normalized by the addition of 5'-deoxyadenosylcobalamin (AdoCbl; 10^-5 mol/l), the specific coenzyme of methylmalonyl coenzyme A mutase. Assays with decreasing concentrations of AdoCbl (10^-5-10^-11 mol/l) suggested a reduced affinity of the mutase apoenzyme for its coenzyme, implicating yet another variant of this heterogeneous disease.

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Coexistence of Defective Activity in Glycine-Cleavage Reaction and Propionly-CoA Carboxylase in the Liver of a Hyperglycinemic Child

Cited by 9 publications

References 12 publications

Acute Neonatal Nonketotic Hyperglycinemia: Normal Propionate and Methylmalonate Metabolism

Acute Neonatal Nonketotic Hyperglycinemia: Normal Propionate and Methylmalonate Metabolism

Propionyl-CoA carboxylase – A review

Congenital Methylmalonic Acidemia: a Variant of the B ‘Non-Responsive’ Form with Evidence for Reduced Affinity of Methylmalonyl-CoA Mutase for its B(12)-Coenzyme

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