FUNCTIONS OF THE LIVER
Protein Metabolism
The liver is the hub for protein metabolism. It synthesizes and
degrades an enormous variety of proteins and peptides and has an essential role in
the production and breakdown of amino acids. Hepatocytes convert amino acids to
keto acids, glutamine, and ammonia via transamination and oxidative deamination reactions.
Removal of ammonia and other nitrogen-containing molecules from the body usually
involves the Krebs-Henseleit cycle, which captures nitrogen in the form of urea.
Thus, with a failing liver (and normal renal function), the blood urea nitrogen
(BUN) concentration typically remains low, whereas nitrogenous wastes (e.g., ammonia)
collect in blood and other tissues and may contribute to hepatic encephalopathy.
[29]
Hepatically synthesized proteins affect every organ in the body.
Included among these proteins are coagulant factors, acute phase reactants, precursors
of hormones, and transport proteins. Albumin accounts for about 15% of the protein
made by the liver. Healthy adults make between 12 to 15 g of albumin each day, and
have an albumin pool containing about 0.50 kg.[30]
The daily production ranges from 120 to 300 mg per kg of body weight, and is highest
in the neonate.[30]
[31]
[32]
[33]
The rate
of albumin production is influenced by dietary amino acids,[34]
[35]
hormonal balance,[36]
and plasma oncotic pressure.[37]
Plasma oncotic
pressure regulates the intravascular albumin concentration. Albumin also has importance
as a plasma transport protein: it binds to many different substances (e.g., drugs,
hormones, metals, metabolites, unconjugated bilirubin, free fatty acids), influencing
their biologic actions and kinetics of elimination.
Alpha-fetoprotein (AFP) is genetically similar to albumin. In
early life, AFP synthesis occurs in the yolk sac, fetal hepatocyte, and cells of
the fetal gastrointestinal tract.[38]
Important
roles of AFP include preserving oncotic pressure and binding free fatty acids. By
the time an infant is 1 year of age, serum albumin has replaced most of the AFP.
After that, increases of plasma AFP usually signal hepatocellular proliferation.
With acute hepatitis, plasma AFP levels rise in nearly all patients (97%).[39]
The largest increases occur in patients with hepatic neoplasms. AFP levels that
exceed 400 ng/mL and progressively increase suggest hepatocellular carcinoma.[38]
[39]
