Liver disease protein synthesis alterations

Alcoholics with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. These factors may be related to decreased protein synthesis and portal hypertension. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. Some alcoholic patients develop hypoglycemia, probably as a result of impaired hepatic gluconeogenesis. Some alcoholics also develop ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

Coagulation factors are proteins with varying but usually short half-lives, (s. tab. 5.12) Their determination allows the assessment of hepatic function. However, the respective half-life has to be considered. Disorders of coagulation factors are therefore important functional parameters in hepatic diseases - both in severe acute and in chronic cases. In liver diseases, there may be a lack of coagulation factors, which is predominantly and primarily caused by a disorder of the hepatocyte synthesis capacity. This lack can also be due to other causes (1.) accelerated catabolism, (2.) altered biosynthesis of inhibitors, (3.) production of abnormal factors, and (4.) increased demand due to intravasal coagulation. 

It is important to distinguish between changes in zinc metabolism which occur as a secondary effect of disease, injury, infection and drug therapy and alterations caused by a primary nutritional zinc deficiency. There is confusion in the literature because a number of unrelated causes can temporarily lower the concentration of zinc in plasma, and this is reported uncritically as evidence of nutritional depletion. Since a high proportion of zinc in plasma is albumin bound, any circumstance which lowers plasma albumin wiil also lower plasma zinc. For example, the changes seen in severe liver disease are primarily caused by a failure of hepatic synthesis of plasma proteins such as albumin. This results in problems in the distribution of zinc and eventual tissue depletion. It is questionable whether zinc supplementation of diet is worthwhile without some restoration of hepatocyte function, by effective treatment of the underlying disease (Mills et al., 1983). 

Most of the common immunological techniques (nephelometry, turbidimetry, etc.) can be used to determine the concentration of transferrin directly. Generally, enhanced turbidimetric assays are now used for transferrin measurements on automated analyzers. Transferrin is decreased in disorders involving reduced or altered protein synthesis (e.g., liver disease) and increased in iron deficiency anemia. A rare condition of near complete absence of plasma transferrin (atransferrinemia) has been reported. 

The D-galactosylceramide jS-D-galactosidase from the liver of a case of Krabbe s disease has been purified. The physical properties of this enzyme were very similar to those of a control from normal liver tissue but the catalytic properties and stability of the enzyme protein were severely affected in the mutant. The findings indicated that the mutation in Krabbe s disease leads to the synthesis of normal quantities of a catalytically and structurally altered protein. 

---