Alfred L. Kennan

Biochemical studies of the developing mammalian fetus: I. Urea cycle enzymes☆

Abstract Four enzymes of the urea cycle have been studied in the livers of fetal, neonatal, and adult rats and pigs. The development of the four enzymes for urea synthesis in the liver of fetal rats was found to be asynchronous, and urea did not appear to be synthesized at a significant rate until late fetal life. All four enzymes were found to be present at significant levels in the liver of the youngest pig embryo studied (28 days). The species difference, which is quite marked, has been discussed in relation to the fetal membranes of the two animals and the maturation of the fetus and newborn. In addition, the relation of these developmental patterns to the theory of recapitulation and the development of the excretory mechanism has also been discussed.

Ammonia detoxication in liver from humans.

Summary The detoxication of ammonia in homogenates of liver from fetal and adult human beings has been studied. Amount of urea synthesized in a day for each case has been calculated from the rate-limiting step of the urea cycle. Similar data are presented for glutamine synthetase and glutamic acid dehydrogenase. Values for human beings have been compared to similar values for the rat, and differences have been discussed.

Glucose repression and induction of enzyme synthesis in rat liver

Summary Glucose has long been known as a key metabolite in intermediary metabolism. Its importance as a regulator of protein synthesis is emphasized by its ability to repress the induced synthesis of threonine dehydrase and ornithine transaminase in rat liver. Simultaneous with its repressive effect, glucose administration per os with casein induces glucose-6-phosphate dehydrogenase after a lag of 12 hr. Neither glucose alone nor casein alone were capable of inducing Zwischenferment. In contrast, glucokinase induction by glucose does not require the concomitant administration of protein. Glucokinase induction was inhibited by puromycin and actinomycin D. Insulin administration along with glucose resulted in some inhibition of induction while glucagon suppressed glucokinase induction more than 80 per cent. Fructose administration resulted in glucokinase induction to about two thirds that with glucose. Other carbohydrates tested gave little or no induction. A model to explain these results based on work with microorganisms is presented.

The free amino acids of amniotic fluid during pregnancy of the rhesus monkey

Abstract The free amino acids of amniotic fluid were analyzed during pregnancy of the rhesus monkey. Samples of amniotic fluid and of fetal and maternal blood were obtained at cesarean section delivery at exactly 50, 75, 100, 125, and 150 days of gestational age. The total value of 19 amino acids in amniotic fluid decreased sequentially with advancing gestational age; the same trend was seen for most of the individual amino acids. Taurine was unique in showing the opposite trend, and demonstrated increasing levels at each subsequent stage of pregnancy. The free amino acids of amniotic fluid did not reflect the levels in the serum of either fetal or maternal blood.

Split products of fibrin in maternal serum in the perinatal period.

Abstract Serum levels of split products of fibrin as an assay for intravascular coagulation or primary fibrinolysis were measured in sera of 84 women in labor, in the immediate postpartum period, and for 3 days after delivery. Split products of fibrin (SPF) were present in 6 of 29 women (21 per cent) during labor, 27 of 84 women (32 per cent) in the immediate postpartum period, and 10 per cent of 33 women 24 to 72 hours after delivery. Serial coagulation studies on 12 normal primigravidas showed that a third had SPF and/or prolonged thrombin times during delivery. Other studies showed high fibrinogen levels, high plasminogen levels, and normal euglobulin clot lysis times, ruling out primary fibrinolysis in these patients. We conclude that local intravascular coagulation is a frequent occurrence during delivery and that acquired bleeding disorders with defibrination represent the extreme of this common event.

Template stability in liver and hepatoma

Abstract The recent advances in the comparative biochemistry of liver tumors of different growth rates were outlined. 1. 1. The four key gluconeogenic enzymes, glucose-6-phosphatase, fructose-1,6-diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase decreased with the increasing growth rate and were absent in the rapidly-growing tumors. It was suggested that the genes for these enzymes may be localized on the same Functional Genome Unit. 2. 2. The RNA amount showed no correlation with growth rate in a spectrum of hepatomas. 3. 3. The incorporation of formate into total hepatoma RNA progressively increased with the increasing growth rate. The incorporation of orotate into RNA was markedly decreased in all tumors examined. The incorporation of formate and orotate into RNA was increased in the regenerating liver. 4. 4. Triamcinolone treatment in control, normal liver caused an increase in total RNA; however, there was no change in the hepatomas. The RNA specific activity was increased in normal liver by steroid injections and it also showed some rise in a slow-growing hepatoma. There was no response in the rapidly-growing liver tumor. 5. 5. The concentration of free amino acid did not correlate with the growth rate of hepatomas. Glucocorticoid injection caused a marked elevation in hepatic amino acid level; however, there was a complete failure of response in all hepatomas examined. 6. 6. Triamcinolone injection caused a progressive increase in hepatic glycogen, nitrogen and free amino acid content and in the activities of glucose-6-phosphatase and fructose-1,6-diphosphatase. There was a failure of response in these biochemical parameters in the kidney cortex. 7. 7. The various biochemical parameters and metabolic responses were correlated with the growth rate of hepatomas.