Pyruvate Carboxylase and Phosphoenolpyruvate Carboxykinase Activity in Leukocytes and Fibroblasts from a Patient with Pyruvate Carboxylase Deficiency

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Normal values are given for the activities of pyruvate carboxylase (E.C., mitochondrial phosphoenolpyruvate carboxykinase (E.C., PEPCK), and citrate synthase (E.C. in fibroblasts, lymphocytes, and leukocytes. Also given are values for these enzymes in the leukocytes and fibroblasts from a severely mentally and developmentally retarded patient with proximal renal tubular acidosis and hepatic, cerebral, and renal cortical pyruvate carboxylase deficiency. In normals, virtually all of the mitochondrial PEPCK and pyruvate carboxylase activity was present in the mononuclear leukocyte fraction of whole venous blood. Cellular fractionation studies with human lymphocytes and fibroblasts demonstrated that all of the PEPCK activity in these cells is mitochondrial. Normal values for pyruvate carboxylase in leukocytes were 0.092 (0.070–0.208) mU/mg protein (n = 5), in lymphocytes 0.154 (0.092–0.262) raU/mg protein (n = 5), and in fibroblasts 136 (0.778–2.19) mU/mg protein (n = 5). The patient with hepatic, renal, and cerebral pyruvate carboxylase deficiency had no detectable activity (<0.009 mU/mg protein) in his leukocytes and 0.018 mU/mg protein in his fibroblasts. Data from an assay for pyruvate carboxylase activity in the patient's fibroblasts show that the activity observed is significant but very close to the lower limits of the assay. Values for PEPCK in normal lymphocytes were 1.42 (0.824–1.88) mU/mg protein (n = 5), in leukocytes 1.68 (1.64–1.72) mU/mg protein (n = 2), and in fibroblasts 5.49 (3.94–6.33) mU/mg protein (n = 6).


The absence of pyruvate carboxylase in the lymphocytes and fibroblasts of a patient with hepatic, renal, and cerebral pyruvate carboxylase deficiency supports the hypothesis that only one form of pyruvate carboxylase exists in the human and suggests that the examination of lymphocytes or fibroblasts for pyruvate carboxylase activity may be a valid method for diagnosing this disease. Furthermore, our results suggest that family studies and prenatal diagnosis may be possible for pyruvate carboxylase deficiency.

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