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ExtractKetotic hyperglycinemia is a syndrome in which elevated concentrations of glycine occur in body fluids of patients who manifest life-threatening episodes of ketoacidosis very early in life. The disorder originally described under this heading is now known to be more reliably categorized by propionic acidemia than by hyperglycinemia. Studies of the metabolism of glycine and of propionate in this condition have been undertaken. Conversion of glycine-1-14 C and of propionate-1-U C to 14 CO 2 has been studied both in vivo and in vitro. Conversion of glycine-2-14 C to serine-3-14 C has been studied in vivo. It was found that the conversion of glycine-1-14 C to CO 2 in vivo was defective in all three of the patients with ketotic hyperglycinemia. At the earliest time points, the specific activities of expired CO 2 in control subjects varied from 25 to more than 60 dpm/jumole, whereas in patients these values did not exceed 10 and were less than 5 in two patients. Conversion of the second carbon of glycine to the third carbon of serine was normal. The relative specific activity of the third carbon was 20. This value was 2-10 times the values found previously in patients with nonketotic hyperglycinemia where this conversion is defective. Conversion of propionate-1-14 C to CO 2 was defective both in vivo and in vitro in patients with ketotic hyperglycinemia and with methylmalonic acidemia. In control subjects, specific activities of the CO 2 expired following injection of propionate-1-14 C approximated 200 dpm/^mole at the earliest time points, whereas in VB the comparable specific activity was close to 0. Activity of propionylcoenzyme A (CoA) carboxylase was absent in the fibroblasts of a patient with ketotic hyperglycinemia. Values of 15-30 dpm/5 mg protein obtained in the patient do not seem to differ significantly from 0, whereas in control subjects the values ranged from 985 to 2655 dpm/5 mg protein. These observations indicate that there are defects in the metabolism of both glycine and propionate in patients with ketotic hyperglycinemia. Speculation

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Tiglic acid, which has not previously been found in human body fluids, was recently detected in the urine of two patients with propionicacidaemia. These patients had a documented defect in the oxidation of propionate. A competition between acrylyl-CoA and tiglyl-CoA for crotonase could explain the accumulation of tiglic acid.

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