Albumin

Albumin functions and features

Introduction to albumin

Preclinical and clinical studies highlight the potential of albumin for a variety of applications, including drug delivery¹

Albumin is a highly versatile protein thanks to both its oncotic and non-oncotic properties. It is the most abundant protein in extracellular fluid and in the blood, representing around half of all serum proteins^2,3. Albumin weighs approximately 67 kDa, is water-soluble, globular and negatively charged at neutral pH³. Albumin is one of the most important proteins¹, with multiple functions including ligand-binding, transportation and compound distribution and metabolism⁴.

In this video, Alastair O’Brien, Professor of Experimental Hepatology at University College London, describes the various roles of albumin in the body. Professor O’Brien describes the oncotic and non-oncotic properties of albumin, including its role in drug transportation, its binding properties and anti-inflammatory effects.

Albumin is a heart-shaped molecule consisting of three domains of similar size, each divided into two subdomains. Within subdomains IIA and IIIA are two important binding sites named Sudlow I and II, which bind hydrophobic compounds, including hydrophobic drugs¹. Figure 1 illustrates the molecular structure of human albumin.

Figure 1. Molecular structure of human serum albumin⁵. Molecular structure of human serum albumin is licensed under CC BY-NC-ND 4.0. The crystal structure (pdb code 1e7i) of human serum albumin shows the six subdomains (IA, IB, IIA, IIB, IIIA and IIIB), the N and C termini, Sudlow’s sites I and II, and the seven long-chain fatty acid (LCFA) binding sites (FA1 to FA7). The heavy atoms of the side chain of residue Cys³⁴ are shown as purple spheres. LCFA binding sites also bind prostaglandins. Cys³⁴ binds reactive oxygen species and reactive nitrogen species, including nitric oxide.

Synthesis and metabolism of albumin

Albumin is synthesised by hepatocytes and excreted into the bloodstream³. Up to 60% of albumin is stored in the interstitial space rather than in circulating blood, lasting just 16–18 hours in circulation, compared with its biological half-life of 19 days¹. The normal concentration of human albumin is 35–50 g/L⁴ and the effective concentration depends on its movement between interstitial and intravascular spaces, and the balance between albumin production and degradation¹.

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Albumin as a prognostic factor

Native human albumin has been demonstrated as a more accurate predictor of 1-year survival in patients with cirrhosis than serum albumin concentration, which is commonly measured in clinical practice¹³

Among the many roles of albumin is its value as a prognostic tool in many clinical settings¹⁴. Low levels of circulating human albumin have been associated with higher risk of morbidity and mortality in the following conditions¹⁴:

• Heart failure
• Cancer
• Malnutrition
• Acute and chronic liver and kidney disease
• Inflammatory conditions

For example in oncology, secreted protein acidic rich in cysteine (SPARC) is absent in normal tissues, but is overexpressed by numerous tumour types¹. SPARC attracts albumin, leading to accumulation within the tumour¹. In albumin-based drug delivery, high levels of SPARC can indicate how efficacious the albumin-based drug delivery system will be at inhibiting cancer proliferation¹.

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Albumin as a colloid for volume replacement

Administration of fluid therapy is common for people who are critically ill or undergoing surgery, to help restore and maintain tissue perfusion¹⁵. Significant risks of fluid therapy relate to pharmacological side effects and under- or over-administration¹⁵. 

There are two main types of intravenous fluids used for volume resuscitation: colloids and crystalloids¹⁵. Figure 5 illustrates the physical differences between the two types.

Figure 5. Crystalloid and colloid solutions (Adapted¹⁶).

Discover the features of crystalloids and colloids, and find out which studies support albumin administration for its approved indications. Simply log in or register for a free Medthority account.

References

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