Human albumin (HA) is the most abundant circulating protein in the plasma of healthy individuals (3.5–5 g/dL) since it represents approximately 50% of the total protein content. HA is a small globular protein (molecular weight: 66.5 kDa), consisting of a single chain of 585 amino acids organised in three repeated homologue domains (sites I, II, and III), each of which comprises two separate sub-domains (A and B). Under physiological conditions, about 10–15 grams of HA are produced in the liver by the hepatocytes every day, with none or very low intracellular storage. Its synthesis is stimulated by hormones, such as insulin, cortisol and growth hormone, while it is inhibited by pro-inflammatory substances, including interleukin-6 and tumour necrosis factor-α1,2. Once released in the circulation, about 30–40% is maintained in the blood stream, while the remainder is distributed in the interstitium, where its concentration is low (1.4 g/dL). The protein leaves the circulation at a rate of 5% per hour, returning to it via the lymphatic system in an amount comparable to the output. This results in a circulatory half-life of approximately 16–18 hours and in a much longer total half-life which varies from about 12 to 19 days in a healthy young adult. HA can be catabolised in many tissues, but mainly in the muscles, liver and kidneys1–4. HA is the main modulator of fluid distribution among the compartments of the body, providing approximately 70–80% of the total plasma oncotic pressure. Two thirds of the oncotic property derives from the direct osmotic effect related to its molecular mass and 1/3 from the Gibbs-Donnan effect, due to the negative net charge of the molecule which attracts positively charged molecules (i.e. sodium and, therefore, water) into the intravascular compartment. However, many other non-oncotic properties which are unrelated to the regulation of fluid compartmentalisation, and are mostly the result of the peculiar structure and conformation of the molecule, have been identified in the last two decades. HA binds and carries a great variety of hydrophobic molecules, such as endogenous (i.e., cholesterol, fatty acids, bilirubin, thyroxina) or exogenous substances (i.e., drugs and toxins), transition metal ions, and gas (nitric oxide [NO]), with consequent implications for their solubilisation, transport, metabolism, and detoxification3,4. HA is also the major source of extracellular reduced sulfhydryl groups, localised at the cysteine-34 (Cys-34) site, which act as potent scavengers of reactive oxygen species (ROS). The antioxidant function resides also in the capability to bind at the N-terminal portion of the molecule several metal ions, including copper, cobalt, nickel, zinc and iron. These ions are therefore inhibited to catalyse many chemical reactions generating free radicals3,5,6. As a result, HA represents the main circulating antioxidant system in the body. The HA molecule also contributes to the stabilisation of the endothelial layer and to the maintenance of the normal capillary permeability probably by reducing oxidative damage and modulating inflammation7,8. Finally, it exerts an antithrombotic effect which appears to be related to the capacity of binding NO at the Cys-34 site with subsequent formation of the complex albumin-NO, thus preventing the rapid inactivation of NO and ultimately prolonging its anti-aggregant effect on platelets9,10.
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Dec 13, 2021
Guowei Lu + 4
Open Access