Liver protein metabolism in man

University dissertation from Stockholm : Karolinska Institutet, Center for Surgical Sciences CFSS

Abstract: Protein depletion is a determinant of clinical outcome in catabolic states. Consequently studies of protein metabolism are necessary to understand the underlying mechanisms. Since the regulation of the synthesis and breakdown of proteins differs between tissues, it is preferable to study protein metabolism on the organ level. The aim of this thesis was to investigate basic and characteristic features of the hepatic amino acid and protein metabolism in man. Liver tissue specimens were obtained during laparoscopic surgery. The free amino acid concentrations and the rates of synthesis of total liver protein and albumin were determined. The impact of two potentially anabolic factors, intravenous nutrition (TPN) and growth hormone (GH), as well as of the surgical procedure on these parameters were investigated. The hepatic free an-dno acid concentration pattern shows some specific features. Aspartate has a higher and glutamine a lower concentration as compared to skeletal muscle. The six most abundant free amino acids in the liver are aspartate, taurine, glutan-dne, glutamate, glycine and alanine. They constitute 88-90 % of the total andno acid concen- tration. In response to TPN, the concentration of the essential amino acids increases. On the other hand, following GH treatment asparate and the essential amino acids decrease in hepatic free concentration. The fractional synthesis rate (FSR) of total liver protein (structural and exported) is 24.7 ± 3.1 %/day, when measured early on during laparoscopic surgery. When the liver protein FSR is measured later during the surgical procedure the respective values are 28 % and 35 % lower. In a prospective study it was shown specifically that the liver protein FSR decreases over time in response to surgery, from 24.1 ± 4.7 %/day after 15 minutes of surgery to 19.0 ± 2.8 %/day (p<0.05) after 50 minutes of surgery. The albumin FSR is 5.9 ± 1.2 %/day and no obvious change is apparent during the course of surgery. The liver protein FSR does not change in response to TPN, whereas pretreatment with GH for five days results in a higher liver protein FSR (22.0 ± 6.9 %/day) than in controls (16.1 ± 3.1 %/day, p<0.05), when measured well into the course of surgery. These results indicate that GH prevents the depression of liver protein synthesis elicited by the surgical procedure, rather than induces a direct stimulation of liver protein synthesis. This interpretation is also supported by ribosome analysis, where a 12 % decrease (p<0.01) in the fraction of polyribosomes (corresponding to protein synthesis activity) in the liver is observed in the control group during surgery, but not in the group that received GH for five days. In summary, liver biopsy specimens obtained during laparoscopic surgery enable studies of hepatic amino acid and protein metabolism in man in vivo. Surgical trauma per se affects liver protein synthesis within an hour of laparoscopic surgery. Short-term TPN and GH in pharmacological doses, both elicit specific alterations in the hepatic free amino acid concentration pattern. TPN does not stimulate liver protein synthesis, while GH prevents the decline in liver protein synthesis associated with the laparoscopic procedure.

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