Albumin

HSA is the single most abundant protein in blood (Table 12.7). Its normal concentration is approximately 42 g T1, representing 60 per cent of total plasma protein. The vascular system of an average adult thus contains in the region of 150 g of albumin. HSA is responsible for over 80 per cent of the colloidal osmotic pressure of human blood. More than any other plasma constituent, HSA is thus responsible for retaining sufficient fluid within blood vessels. It has been aptly described as the protein that makes blood thicker than water.

Albumin molecules also temporarily leave the circulation, entering the lymphatic system, which harbours a large pool of this protein (up to 230 g in an adult). Lower quantities of albumin are also present in the skin.

In addition to its osmoregulatory function, HSA serves a transport function. Various metabolites travel throughout the vascular system predominantly bound to HSA. These include fatty acids, amino acids, steroid hormones and heavy metals (e.g. copper and zinc), as well as many drugs.

HSA is a 585 amino acid, 65.5 kDa polypeptide. It is one of the few plasma proteins that are unglycosylated. A prominent feature is the presence of 17 disulfide bonds, which help stabilize the molecule's three-dimensional structure. HSA is synthesized and secreted from the liver, and its gene is present on human chromosome number 4.

Table 12.7 The major plasma proteins of known function found in human blood

Normal plasma Molecular

Table 12.7 The major plasma proteins of known function found in human blood

Normal plasma Molecular

Protein

concentration (g l 1)

mass (kDa)

Function

Albumin

35-45

66.5

Osmoregulation transport

Retinol-binding protein

0.03-0.06

21

Retinol transport

Thyroxine binding globulin

0.01-0.02

58

Binds/transports thyroxine

Transcortin

0.03-0.04

52

Cortisol and corticosterone transport

Ceruloplasmin

0.1-0.6

151

Copper transport

Haptoglobin

Binds and helps conserve haemoglobin

type 1-1

1.0-2.2

100

type 2-1

1.6-3.0

200

type 2-2

1.2-2.6

400

Transferrin

2.0-3.2

76.5

Iron transport

Hemopexin

0.5-1.0

57

Binds haem destined for disposal

ß2-Microglobulin

0.002

11.8

Associated with human leukocyte antigen

histocompatibility antigen

y-Globulins

7.0-15.0

150

Antibodies

Transthyretin

0.1-0.4

55

Binds thyroxine

HSA is used therapeutically as an aqueous solution; it is available in concentrated form (15-25 per cent protein) or as an isotonic solution (4-5 per cent protein). In both cases, in excess of 95 per cent of the protein present is albumin. It can be prepared by fractionation from normal plasma or serum, or purified from placentas. The source material must first be screened for the presence of indicator pathogens. After purification, a suitable stabilizer (often sodium caprylate) is added, but no preservative. The solution is then sterilized by filtration and aseptically filled into final sterile containers. The relative heat stability of HSA allows a measure of subsequent heat treatment, which further reduces the risk of accidental transmission of viable pathogens (particularly viruses). This treatment normally entails heating the product to 60 °C for 10 h. It is then normally incubated at 30-32 °C for a further 14 days and subsequently examined for any signs of microbial growth.

HSA is used as a plasma expander in the treatment of haemorrhage, shock, burns and oedema, as well as being administered to some patients after surgery. For adults, an initial infusion containing at least 25 g of albumin is used. The annual world demand for HSA exceeds 300 t, representing a market value of the order of US$1 billion.

Despite screening of raw material and heat treatment of final product, HSA derived from native blood sometimes (though rarely) will harbour pathogens. rDNA technology provides a way of overcoming such concerns, and the HSA gene and cDNA have been expressed in a wide variety of microbial systems, including E. coli, Bacillus subtilis, S. cerevisiae, Pichia pastoris and Aspergillus niger. (Its lack of glycosylation renders possible production of native HSA in prokaryotic and eukaryotic systems.) However, HSA's relatively large size, as well as the presence of so many disulfide bonds, can complicate recombinant production of high levels of correctly folded products in some production systems. The main stumbling block in replacing native HSA with a recombinant version, however, is an economic one. Unlike most biopharmaceuticals, HSA can be produced in large quantities and inexpensively by direct extraction from its native source. Native HSA currently sells at US$2-3 per gram. Although it can be guaranteed blood pathogen free, recombinant HSA products will find it difficult to compete with this price.

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