Abstract
The effects of hypophysectomy on amino acid metabolism were studied both in vivo and in the perfused rat liver. Hypophysectomized rats exhibited elevated plasma urea concentrations and reduced plasma and liver amino acid levels, while perfused livers from these animals showed enhanced rates of amino acid uptake. No effect of hypophysectomy on hepatic amino acid transport was noted, suggesting that the enhanced hepatic amino acid uptake resulted from an increased flux through the metabolic pathway (or pathways) operating in the liver. Livers from hypophysectomized rats produced substantially more glucose and urea than livers from normal animals when both were perfused with medium containing various levels of amino acids. The rate of glucose synthesis from either labeled alanine, pyruvate, glutamate, or aspartate was stimulated 3- to 4-fold in livers from hypophysectomized rats, showing an increased flux of amino acids through the pathway of gluconeogenesis. Treatment of hypophysectomized rats with growth hormone for 2 days returned the rate of gluconeogenesis from alanine toward normal, although the reversion was incomplete. The data suggested that the enhanced hepatic utilization of amino acids following hypophysectomy resulted from increased metabolism of the compounds in the liver, involving increased fluxes through the pathways of gluconeogenesis and ureogenesis.
Highlights
MethodsBlood plasma and perfusate plasma were analyzed for urea by the urease method of Searcy e2 al. [22] and for glucose by the glucose oxidase method [23]
The effects of hypophysectomy on amino acid metabolism were studied both in vivo and in the perfused rat liver
Treatment of hypophysectomized rats with growth hormone for 2 days returned the rate of gluconeogenesis from alanine toward normal, the reversion was incomplete
Summary
Blood plasma and perfusate plasma were analyzed for urea by the urease method of Searcy e2 al. [22] and for glucose by the glucose oxidase method [23]. Liver glycogen was extracted as described by Walaas and Walaas [24] and the glucose resulting from hydrolysis was measured and expressed as glucose equivalents per unit wet weight of tissue. Liver protein and RNA contents were estimated by the Folinphenol reagent method of Lowry et al [25] and by the alkaline hydrolysis method [26], respectively. Powdered liver samples and aliquots of plasma and perfusate were prepared for amino acid analysis by precipitation of protein with 1% picric acid containing norleucine as internal standard [27]. Uptake of free amino acids by the liver was calculated from the measured differences in the levels of individual amino acids in perfusate plasma before and after perfusion
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