David Yi-Yung Hsia

Variability in the clinical manifestations of galactosemia.

These studies showed that in this patient the block of steroid ll-beta hydroxylation was incomplete. CortisoI production appeared to be maximal in the control period since it was not increased by ACTH administration. No conversion of cortisol to l l-deoxy compounds occurred which showed by a direct means that cortisol was not a source of these steroids in the urine. A metabolite of Compound S, 6-betahydroxy Compound S, is described for the first time in human urine.

Epinephrine metabolism in phenylketonuria.

Summary Data have been presented showing a decrease of norepinephrine and epinephrine in the plasma and of dopamine, norepinephrine, and epinephrine in the urine of phenylketonuric children. These changes were reversed when the patients were treated with a low-phenylalanine diet. Since plasma tyrosine levels remained unchanged, this decrease appears to be caused by inhibition of dopa decarboxylase by the derivatives of phenylalanine. This would provide further in vivo evidence that the pyridoxal-phosphate dependent decarboxylases represent related or identical enzyme systems.

Inhibition of glucuronosyl transferase by steroid hormones

Abstract Pregnanediol, Δ 1 -17α-methyltestosterone, testosterone, estriol, 17α-methyltestosterone, progesterone, 17α-ethyl-19-nortestosterone, and 6α-methylprogesterone inhibited guinea pig liver glucuronosyl transferase using o -aminophenol, p -nitrophenol, and 4-methylumbelliferone as aglycones, while cholesterol, pregnanedione, pregnenolone, 17α-hydroxyprogesterone, cortisone, estradiol, estrone, and methylandrostenediol did not. Pregnanediol glucuronide and estriol glucuronide also were inhibitors. Microsomes prepared as described contained little or no β-glucuronidase or uridine diphosphoglucuronic acid pyrophosphatase activity. Kinetic studies gave a K m for glucuronosyl transferase of 1.92 × 10 −4 using o -aminophenol as aglycone. The kinetics of pregnanediol glucuronide and 17α-ethyl-19-nortestosterone inhibition were mainly competitive in type with K i of 3.24 × 10 −4 and 2.52 × 10 −4 , respectively.

The metabolism of 5-hydroxytryptamine (serotonin) in the newborn.

Infants have lower values of 5-hydroxytryptamine than do adults. This is related to the age and weight of the infants; adult values can be achieved by the administration of pyridoxine. Newborn rats have low concentrations of 5-hyroxytrypiophan decarboxylase in their kidneys; this was prolonged when their mothers were placed on a pyridoxine-deficient diet. Low levels of 5-hydroxytryptamine represent immaturity of the apoenzyme at birth and a relative deficiency of pyridoxine.

Clinical variants of galactosemia

Abstract This paper summarizes current thinking on the methods for the assay of galactose-1-phosphate uridyl transferase and how they are being used to detect clinical variants of galactosemia.

Galactosemia: A study of twenty-seven kindreds in North America*

The present paper reports on the enzyme studies performed on 421 individuals in twenty‐seven kindreds which include twenty‐nine sibships containing galactosemic individuals.

Galactose-I-phosphate uridyltransferase in red and white blood cells.

Abstract The assay of galactose-1-phosphate uridyltransferase (E.C. 2.7.7.12: UDP-glucose: α- d -galactose-1-phosphate uridyltransferase) in red and white cells of blood is reported using [14C]galactose-1-phosphate and UDPglucose as substrates and measuring the 14C activity in the nucleotides. The reaction requires for optimal activity a concentration of 3.2 mM galactose-1-phosphate and 1.6 mM UDPG with the pH maintained at 8.40.

Studies on mechanism for decreased lipoprotein lipase in cystic fibrosis of the pancreas

Fifty children with cystic fibrosis of the pancreas were found to have a lipoprotein lipase (LpL) activity of 0.15±0.06 mEq. per milliliter per minute as compared with a value of 0.30±0.04 in 30 normal comparable controls. This difference could not be explained on the basis of sex, age, weight, length, or body surface. Ten parents of fibrocystic children as well as 10 siblings were found to have normal values for LpL. Ten marantic children with congenital heart disease showed normal LpL values, but 10 patients with a celiac syndrome had the low value of 0.17±0.05 mEq. per milliliter per minute. A dietary study was undertaken in 10 normal boys whose LpL values were normalwhile receiving a regular diet. After 10 days of low-fat (5 Gm.) isocaloric diet, the LpL activity fell significantly. After 2 additional weeks on a normal diet, the values returned to normal. These studies indicate that the decrease of LpL in patients with cystic fibrosis is a result of a lack of stimulation of enzyme production due to malabsorption of triglycerides.

Polyribosomes from L cells

Abstract High yields of polyribosomes from suspensions of L cells and other types of cell rich in intracellular hydrolases have been obtained after disruption of the cells by nitrogen cavitation. Such polyribosome preparations have been used for in vitro amino acid incorporation into polypeptides.

Enzyme studies during lymphocyte stimulation with phytohemagglutinin in Down's syndrome

Abstract Lymphocytes obtained from the peripheral blood of patients with trisomic Downs syndrome and controls were stimulated with PHA. Acid phosphatase, alkaline phosphatase, and glucose-6-phophate dehydrogenase were found to be elevated when compared with controls. Despite the increased activity in Downs syndrome, the ratio of Downs to controls remained constant throughout the experiment. The lymphocytes of both groups responded in a similar fashion when the incorporation of tritiated thymidine was measured.