Studies of the regulation of plasma protein synthesis in man using stable isotopes
Metabolism of the transport protein albumin is known to be regulated by long-term nutrient status. To assess the short-term response to feeding, studies were performed which measured the rate of albumin synthesis once after an overnight fast and once after one of two feeding regimens consisting of five small hourly meals or one large meal. Albumin synthesis increased by approximately 25% and 31% above the fasting value for the small meals and large meal regimens respectively, thus demonstrating that albumin synthesis is acutely sensitive to nutrient intake. A supplementary animal experiment indicated that this response is part of an overall increase in liver protein synthesis. Elevated plasma fibrinogen concentration has been implicated as a risk factor for the development of cardiovascular disease. As cigarette smokers are known to have a significantly raised plasma fibrinogen concentration, studies were performed to investigate the metabolic mechanism responsible for this by comparing the rate of fibrinogen synthesis in smokers and non-smokers and smokers who had abstained from smoking for 14 days. Smokers had a significantly greater absolute rate of fibrinogen synthesis (mean SD, 21.5 1.9 versus 16.0 1.4 mg/kg/d, p<0.05). Although smokers were found to have moderate leucocytosis, there did not appear to be any increased metabolic activity of lymphocytes. In a separate group of smokers, abstention from smoking for 14 days resulted in a significant reduction in plasma fibrinogen concentration of 19%. The fractional rate of fibrinogen synthesis also decreased significantly by 14% suggesting that a substantial part of the hyperfibrinogenaemia observed in smokers is the product of increased output by the liver.