Beulah M. Woodfin

Neuropathology of ornithine carbamyl transferase deficiency

SummaryNeuropathologic findings in two cases of ornithine carbamyl transferase (OCT) deficiency are presented. In one, a boy 3 days old, the only abnormality related to the enzyme defect was metabolic gliosis which was unusual in distribution being present mainly in the brain stem. In the other case, a girl who died at the age of 2 3/12 years, the brain showed metabolic gliosis in typical location, widespread ulegyria, and moderate atrophy of the internal granular layer in the cerebellum accompanied by development of expansions of Purkinje cell dendrites. Case 2 demonstrates how rapidly changes previously demonstrated in the cerebral cortex after a few months of illness can proceed to massive hemispheric destruction. By now ulegyria has been observed in several disorders of the urea cycle.

Accelerated glycolysis in early hypertensive left ventricular hypertrophy.

Changes in energy metabolism have been demonstrated in established left ventricular hypertrophy (LVH). It is not known if cardiac energy metabolism is shifted toward anaerobic pathways during the early stage of hypertensive LVH. Accordingly, glycogen, pyruvate, and lactate levels from left ventricular homogenate were measured in 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Systolic arterial pressure and left ventricular weight were determined to establish hypertensive state and LVH, respectively. The glycogen and pyruvate levels in SHR versus WKY were lower by 19 (p < 0.05) and 12% (NS), respectively. The lactate level in the SHR was 14% higher (p < 0.05) than in WKY. The lactate/pyruvate ratio in the SHR was higher than in the WKY, but did not reach statistical significance. These data suggest that the anaerobic metabolism is induced early in the development of hypertension, before the development of substantial LVH.

Altered OCTase location in the influenza BLee virus model for Reye's syndrome☆

Abstract OCTase deficiency has been reported to be associated with Reyes syndrome by some observers, while others report no abnormalities. In this paper, we discuss the OCTase levels in an experimental mouse model of Reyes syndrome. In all but one mouse, total liver OCTase was found to be in the normal range. A significant fraction of the OCTase, however, was found in the cytosol, while little was found in the cytosol of control mice. In addition, up to a 10-fold increase of OCTase was observed in the serum of experimental mice. This indicates that, although total enzyme remains the same, the mitochondrial portion of the urea cycle is disrupted. It is suggested that serum OCTase levels may be of value in the differential diagnosis of Reyes syndrome.

A NEW PURIFICATION PROCEDURE FOR PIG HEART FUMARASE

ABSTRACT. Pig heart fumarase was thought for some years to be a homopolymer with four subunits. Heterogeneity was demonstrated by electrofocusing, and polydispersity by chromatography, both in phosphate systems. In this paper, evidence is presented that the heterogeneity may be a function of the anionic environment. Since the established purification procedures for pig heart fumarase expose the protein to high concentrations of phosphate and sulfate, both inhibitors of the enzymic activity, a new purification procedure has been undertaken.

Displacement of hepatic ornithine carbamoyltransferase from mitochondria to cytosol in Reye's Syndrome

In two patients with fatal Reyes Syndrome, total ornithine carbamoyltransferase (OCTase) activity in the liver was 50 and 75% of that found in three control livers. The levels of enzymatic activity would not be expected to have resulted in the 7- and 17-fold elevations in plasma ammonia levels found in the patients. Levels of 47 and 60% of the OCTase activity, however, were found in the cytosolic fraction compared to an average of 7% for control livers. Thus, the amount of enzymatic activity in the mitochondrial fractions was only 20 and 30% of that found in control mitochondrial fractions. This study suggests that, if only mitochondrial OCTase is active in the urea cycle, the decreases in functional enzyme found in Reyes Syndrome may be considerably greater than that reflected in total enzyme assays.

A fatal variant of human ornithine carbamoyltransferase is stimulated by Mg2

Biochemical studies of a female who died at 2 years of age from a possible genetic variant of ornithine carbamoyltransferase (OCTase) deficiency are reported. The patient had severe psychomotor retardation with plasma ammonia levels throughout life reaching as high as 500 mumole/liter. The average OCTase level in the patients liver was 2% of that in normal livers. Preincubation with 0.05 M MgCl2 resulted in a 570% increase in OCTase activity (13% of control). Citrate synthase and carbamoyl-phosphate synthase I were present at essentially normal levels. Unusual Mg2+ requirements have not been recognized in previous reports of OCTase deficiency, suggesting a genetic variant in this patient.