- Glucose homeostasis
- Fat metabolism
- Amino acid metabolism and urea synthesis
- Synthesis of plasma proteins such as albumin and blood clotting factors
- Trace element homeostasis
- Alcohol metabolism
- Storage of Iron
Plasma protein synthesis: Two of the most important proteins synthesized by the liver are:
- Albumin and
- Blood clotting factors
- Albumin: It makes up 50% of the protein found in plasma. Two major roles of albumin are:
- The high concentration of albumin results in it making a large contribution to the osmomolarity of the plasma, preventing oedema. Oedema and ascites are signs of chronic liver disease reducing the capacity for albumin synthesis. Protein malnutrition can lead to depleted levels of albumin and subsequent oedema. Kidney disease can also deplete albumin through excessive secretion with similar results.
- Binding of small molecules- Albumin is a major carrier of the other molecules in the plasma, especially hydrophobic molecules and metal ions. Albumin has several sites of binding hydrophobic molecules. The binding is non-specific and relatively weak, but this is still important quantitatively due to the high concentration of albumin in plasma. Important molecules carried by the albumin include: free fatty acids, steroid hormones, billirubin and hydrophobic drug molecules. Another example of a plasma protein synthesized by the liver with a role in metal transport is transferring.
- Blood Clotting Factors: Blood clotting factors are proteases that act upon one another in a cascade when activated, ultimately converting fibrinogen to fibrin which is insoluble and forms the blood clot. It prevents the further blood loss, maintaining haemostasis.
Almost all of the blood clotting factors are synthesized by the liver. Liver diseases can depress the clotting system enough to cause severe tendency to bleed. Liver synthesis of four of the most important clotting factors prothrombin, factors VII, IX and X- is vitamin K dependent. Lack of the fat-soluble Vitamin K can also lead to a serious tendency to bleed. Normally, vitamin K is made by intestinal bacteria and absorbed with dietary fat. Liver disease is one of the main causes of vitamin K deficiency. Lack of bile secretion causes poor fat absorption and, thus, poor vitamin K uptake.
- It is obviously important that blood clotting does not occur when it is not required. Antiprothrombin III is the major anticoagulation plasma protein, with heparin co-factor II. Protease inhibitors prevent blood clotting factors acting inappropriately.
- The anticoagulation drug, heparin, strongly activates antithrombin.
- Many of the proteins involved in blood clotting are modified, post-translationally, carboxylglutamyl (Gla) residues. The proteins with Gla residues are effective at binding Ca2+ ions. Ca2+ is important for clotting factor interactions with other proteins and for enhancing their catalytic activity.
The post-translational modification is vitamin K dependent. Vitamin K is an essential co-factor for the carboxylase enzyme responsible, located on the luminal side of the rough ER. Some anticoagulants inhibit the carboxylase reaction by interfering with the vitamin K co-factor.