Metabolism of Glyoxylate in Nonketotic Hyperglycinemia

Abstract

Hyperglycinemia is an error of amino acid metabolism in which there are increased amounts of glycine and normal amounts of other amino acids in blood, urine, and cerebrospinal fluid. There are a t least two different types of hyperglycinernia. We recently reported on the metabolism of glycine in nonketotic hyperglycinernia [I]. A defect was found in the formation of14C02 from glycine-1-14C and in the conversion of the carbon 2 of glycine to the carbon 3 of serine. These findings were consistent with a defect in a n enzyme system catalyzing the formation of CO, and hydroxymethyltetrahydrofolate from glycine, but did not exclude a defect in glycine oxidase. It was decided, therefore, to assess the metabolism of glyoxylate in nonketotic hyperglycinernia.T h e conversion of glyoxylate-1-14C to 14C02 ( fig. 1) was similar to that of glycine-1-14C. Oxidation to CO, was rapid in control subjects, but in the patient, a flat curve was obtained. The transfer of isotope to serine was slower in the patient than in the control subjects. No isotope was found in carbon 3 of serine in the patient, while a significant amount of the isotope of carbon 3 of glyoxylate was incorporated into carbon 3 of serine in the control subjects.The data obtained indicate that the pathway of preference for the metabolism of glyoxylate is transamination to glycine and rule out a defect in glycine oxidase in nonketotic hyperglycinernia. SpeculationThe data obtained in this investigation contribute to the hypothesis that the enzymic defect in nonketotic hyperglycinernia is situated in the reaction that forms CO,, NH, and F H 4 C H 2 0 H from glycine.This reaction is probably catalyzed by a n enzyme system with a number of component enzymes. Further investigations will be necessary in order to determine exactly the enzyme that is deficient.

Glycine: Inhibition from the Sacrum to the Medulla

“…I~ patients survive the early months, mental retardation, decerebrate rigidity and hypertonus are observed in the later phases o~ their lives. Tracer stUdies in some o~ these patients show a normal glycine oxidation (Gerritsen et al, 1969) and a block in the glycine cleavage system in both the brain and the liver (Perry et al, 1975a;Tada et al, 1974;Trijbels et al,1974). An increiSe-rn glycine levelS-or-cerebrospinal ~lui~ and blood is also observed (Scriver et al, 1975;Perry et al, 1975b) • The CSF to blood p,lycine ratio -rs higher than in-cOntrol sub,jects, which ~its the criterion used by some physicians to classify a disease as a genetic glycinemia, as opposed to other syndromes which indirectly result in high blood glycine levels (Applegarth and Poon, 1975).…”

The subcellular distribution of rat liver l-alanine–glyoxylate aminotransferase in relation to a pathway for glucose formation involving glyoxylate

“…The reverse reaction with glycine and pyruvate is barely detectable in crude liver homogenates (Rowsell et al, 1969b), and not at all with L-alanineglyoxylate aminotransferase purified from human liver (Thompson & Richardson, 1967). It seems likely therefore that the enzyme does operate to convert glyoxylate into glycine, a process that undoubtedly can occur in vivo in the rat (Weinhouse & Friedman, 1951;Weissbach & Sprinson, 1953) and in man (Gerritsen et al, 1969).…”

A Patient with Nonketotic Hyperglycinemia: Biochemical Findings and Therapeutic Approaches

“…Gerritsen et al [14] supposed originally that nonketotic hyperglycinemia was associated with a defect i n the glycine oxidase system; however, later such a defect was ruled out [15]. Thereafter, Ando et al [3] demonstrated a defect in viuo in the formation of l4CO2 from (I-l4C)glycine and a complete deficiency in the conversion of (2-1")glycine to (3-14C)serine.…”