Propionate Metabolism in Cells Cultured from a Patient with Methylmalonic Acidemia

Morrow, Grant; Mellman, William J.; Barness, L A; Dimitrov, Nikolay V.

doi:10.1203/00006450-196905000-00005

Cited by 26 publications

(2 citation statements)

References 6 publications

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“…Cells from patients with metabolic blocks along this pathway should not be able to metabolize radioactive propionate in this manner, unless there is sufficient incorporation via the acrylyl pathway. The small amount of lactate found in the MMA cells by Morrow et al (1969) could arise from this route.…”

mentioning

confidence: 99%

Detection of inborn errors of metabolism

Hill

Goodman

1974

Clinical Genetics

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Human fibroblasts, cultured on glass microscope slides, were examined autoradiographically for their ability to incorporate radioactivity from Na‐propionate‐l‐ 14C into TCA‐insoluble cell material. Cells from patients with propionic acidemia (PA) and methylmalonic acidemia (MMA), both B12‐sensitive and B12‐insensitive, incorporate little or no radioactivity and thus can be readily distinguished from cells of a number of individuals with no defects in this pathway. Incorporation in cells from non‐MMA individuals is significantly enhanced in a basal medium by high levels of glucose. This procedure should be readily adaptable for use in screening for disorders of propionate metabolism, particularly before birth.

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confidence: 99%

Detection of inborn errors of metabolism

Hill

Goodman

1974

Clinical Genetics

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“…Cultivation of human fibroblast cell strains provides a unique system for in vitro metabolic studies, and the use of explants from human skin biopsies has permitted the precise definition of several inborn errors of metabolism (1)(2)(3). Carbohydrate metabolism in cells in culture has been studied under various experimental conditions (4-7), and extensive reviews by Levintow and Eagle (8), Paul (9), and Cristofalo, Howard, and Kritchevsky (10) have documented that the metabolic processes of cells in tissue culture were consistently similar. Investigations in this laboratory have described an alteration in the oxidation of labeled glucose in the tissue culture fibroblasts (CC-69) derived from a skin biopsy from an infant with an unknown form of ketoacidosis (11,12).…”

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An Alteration in Glucose Metabolism Associated with a Defect in Ketone Body Metabolism

Tildón

1973

Proc. Natl. Acad. Sci. U.S.A.

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Skin fibroblasts (CC-69) cultured from a patient with a unique syndrome of ketoacidosis associated with coenzyme A transferase (EC 2.8.3.5) deficiency showed an altered pattern of carbohydrate metabolism. These cells used glucose at a rate significantly less than controls (125 against 680 nmol/mg per hr). The oxidation of glucose to 14CO2 by these cells was also significantly di- 175. This change was not due to new enzyme formation because incubation with puromycin had no effect on the increased use of glucose. Mixing experiments demonstrated no transfer of a permeable inhibitor or activating substances. In view of the deficiency of coenzyme A transferase in these cells, the data suggest an indirect regulatory role for this enzyme in peripheral tissue glycolysis.Cultivation of human fibroblast cell strains provides a unique system for in vitro metabolic studies, and the use of explants from human skin biopsies has permitted the precise definition of several inborn errors of metabolism (1-3). Carbohydrate metabolism in cells in culture has been studied under various experimental conditions (4-7), and extensive reviews by Levintow and Eagle (8), Paul (9), and Cristofalo, Howard, and Kritchevsky (10) have documented that the metabolic processes of cells in tissue culture were consistently similar.Investigations in this laboratory have described an alteration in the oxidation of labeled glucose in the tissue culture fibroblasts (CC-69) derived from a skin biopsy from an infant with an unknown form of ketoacidosis (11,12). Subsequent reports have shown that the ketoacidosis in that infant was associated with a deficiency of Succinyl-CoA: 3-ketoacid CoA transferase (CoA transferase) (EC 2.8.3.5) (13,14). The continued study of this cell strain offers a unique opportunity for the understanding of cellular metabolism.It is the purpose of this report to further describe the alterations and irregularities in glucose metabolism in CC-69 cells and to contrast the metabolic processes in those cells with those in tissue culture fibroblast explants from normal controls. These data suggest an interrelationship between glucose metabolism and the oxidation of ketone bodies. MATERIALS AND METHODSSkin fibroblasts were grown from skin obtained by a punch biopsy from an infant with severe ketoacidosis who was shown to have a deficiency in CoA transferase (14). Control cell lines were derived from the foreskins and diagnostic skin biopsies of children with no evidence of ketoacidosis. All fibroblasts were maintained in culture in 8-oz bottles in Eagle's Minimal Essential Medium (Grand Island Biological Co., Grand Island, N.Y.) with added glutamine (1.8 mM), penicillin (56 ug/ml), streptomycin (90,ug/ml), and fetal-calf serum (10%). Periodic tests for contamination by bacteria and mycoplasma were negative.For metabolic studies, cells were grown directly in 25-ml tissue culture reaction flasks (Kontes Glass Co., Vineland, N.J.), and were used 3-5 days after replating. After the medium was decanted and the adherent cell layer ri...

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Disorders of Organic Acid Metabolism

Tanaka

1975

Biology of Brain Dysfunction

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Propionate Metabolism in Cells Cultured from a Patient with Methylmalonic Acidemia

Cited by 26 publications

References 6 publications

Detection of inborn errors of metabolism

Detection of inborn errors of metabolism

An Alteration in Glucose Metabolism Associated with a Defect in Ketone Body Metabolism

Disorders of Organic Acid Metabolism

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