Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Liver
The Role of the Liver in Protein Metabolism

The Liver plays a central role in Protein METABOLISM, performing several core Functions: the Synthesis of specific Plasma Proteins; The production of urea and uric acid; the synthesis of Choline and creatine; and the Transamination and Deamination of Amino acids, which are essential for amino acid interconversions, Gluconeogenesis, and ketone body formation. All plasma albumin*, 75–90% of $\alpha$-globulins, and 50% of $\beta$-globulins are synthesized by hepatocytes. Only $\gamma$-globulins are produced outside hepatocytes—by the macrophage system, which includes hepatic macrophages (Kupffer Cells)—though the liver remains a primary site for $\gamma$-globulin production. Furthermore, the liver is the sole organ responsible for synthesizing vital Blood-clotting proteins such as prothrombin, fibrinogen, proconvertin, and proaccelerin.

* A healthy human liver can synthesize 13–18 g of albumin daily.

In liver diseases, analyzing the protein fractions of Blood Plasma (or serum) is often valuable for both DIAGNOSTIC AND PROGNOSTIC purposes. It is well established that pathological processes in hepatocytes severely impair their synthetic capacity. As a result, plasma albumin levels drop sharply, which can lead to a decrease in plasma oncotic pressure, edema, and subsequently ascites. Notably, in liver cirrhosis complicated by ascites, serum albumin levels are 20% lower than in cirrhosis without ascites.

Impaired synthesis of certain coagulation factors during severe liver diseases can lead to hemorrhagic manifestations.

Liver damage also disrupts the deamination of Amino Acids, leading to elevated concentrations in both blood and urine. For instance, while normal Amino Acid Nitrogen levels in blood serum range from approximately 2.9 to 4.3 mmol/L, severe liver disease (such as atrophy) can cause this value to surge up to 21 mmol/L, resulting in Aminoaciduria. For example, in acute liver atrophy, the daily urinary excretion of Tyrosine can reach 2 g (compared to a normal range of 0.02–0.05 g/day).

In The Human Body, urea is synthesized primarily in the liver. This process requires a significant expenditure of energy, consuming 3 molecules of ATP per molecule of urea produced. When liver disease reduces intracellular ATP levels in hepatocytes, urea synthesis is impaired. A telling diagnostic indicator in such cases is the serum urea nitrogen to amino acid nitrogen ratio. Normally 2:1, this ratio drops to 1:1 in severe liver damage.

The liver is also the primary site for uric acid production, as it contains high concentrations of xanthine oxidase, the enzyme that converts oxypurines (hypoxanthine and xanthine) into uric acid. Additionally, the liver plays a crucial role in creatine synthesis. The body obtains creatine from two sources: exogenous creatine from dietary intake (such as meat and liver) and endogenous creatine synthesized within Tissues. Creatine is synthesized predominantly in The Liver and transported via the bloodstream to Muscle tissue, where it is phosphorylated into creatine phosphate, which subsequently yields creatine.