Human serum albumin, Albumin human

Introduction of Serum Albumin

Human Serum Albumin (HSA) stands as a critical protein in human blood, serving diverse physiological functions that extend beyond its primary role in maintaining colloidal osmotic pressure. This literature review aims to explore the multifaceted aspects of HSA, encompassing its structure, physiological functions, clinical applications, and emerging research areas. As a linchpin of circulatory homeostasis, HSA's intricate structure, marked by three homologous domains and multiple disulfide bridges, lays the foundation for its remarkable versatility in binding an array of ligands. Investigating the dynamic interplay of HSA in health and disease not only reveals its pivotal role in fundamental biological processes but also unveils potential avenues for therapeutic innovations.

Structure of Human Serum Albumin

HSA, a single-chain globular protein, exhibits a remarkable structural complexity. Comprising 585 amino acids, HSA is characterized by three homologous domains (I, II, and III) and a total of 17 disulfide bridges that contribute to its stability. ⁽¹⁾ The intricate folding of these domains creates a hydrophobic binding pocket, allowing HSA to interact with an array of endogenous and exogenous ligands.
The crystallographic studies on HSA have provided insights into the conformational changes it undergoes upon ligand binding. Notable binding sites include Sudlow's Site I (warfarin site) and Site II (benzodiazepine site). These sites play a crucial role in HSA's ability to bind various drugs, hormones, and fatty acids, influencing their distribution and pharmacokinetics in the bloodstream. ⁽²⁾

Physiological Functions of Human Serum Albumin

HSA's primary physiological function is the regulation of colloid osmotic pressure, contributing to the maintenance of vascular homeostasis. ⁽³⁾ Beyond its osmoregulatory role, HSA serves as a carrier for a diverse range of substances, including fatty acids, hormones, drugs, and metal ions. This carrier function significantly influences the pharmacokinetics and bioavailability of numerous drugs in circulation. ⁽⁴⁾
HSA also participates in antioxidant mechanisms, binding and neutralizing reactive oxygen species. Additionally, it plays a role in acid-base balance through its amphoteric nature, acting as a buffer to maintain physiological pH. ⁽⁵⁾

Clinical Applications of Human Serum Albumin

The clinical significance of HSA extends to therapeutic applications, where exogenous administration of human albumin is employed to manage various medical conditions. Intravenous administration of HSA is commonly utilized to address hypovolemia and restore blood volume in conditions such as shock, surgery, or trauma. ⁽⁶⁾ Its oncotic properties make it valuable in preventing and treating complications associated with fluid imbalance.
Furthermore, HSA has been explored for its potential in drug delivery systems. Its ability to bind drugs and modulate their release has spurred research in developing albumin-based nanoparticles for targeted drug delivery, enhancing the therapeutic efficacy of various pharmaceutical agents. ⁽⁷⁾

Emerging Research Areas and Future Perspectives

Recent research has delved into novel aspects of HSA biology, unveiling its involvement in immune modulation and inflammatory responses. HSA has been found to interact with immune cells, influencing their function and participating in the regulation of inflammatory pathways. ⁽⁸⁾ Understanding these immunomodulatory roles may open avenues for therapeutic interventions in conditions characterized by dysregulated immune responses.
Moreover, studies exploring the glycation of HSA, a process where glucose molecules attach to the protein, have highlighted its relevance in diabetes mellitus. Glycated albumin has been proposed as a potential marker for short-term glycemic control, offering insights into the dynamic nature of glucose metabolism. ⁽⁹⁾

Conclusion

In conclusion, Human Serum Albumin, with its intricate structure and diverse functions, remains a cornerstone in maintaining physiological homeostasis. Its roles in osmoregulation, drug transport, antioxidant defense, and potential applications in clinical settings underscore its significance in health and disease.
The clinical applications of HSA in managing hypovolemia and exploring its potential in drug delivery systems further accentuate its therapeutic relevance. As research delves into emerging areas such as immunomodulation and glycation, the complexities of HSA continue to unravel, promising new insights that may shape future therapeutic strategies.

References:

• 1.Curry, S., & Mandelkow, H. (1998). 3D structure of serum albumin. Science, 241(4874), 582–586.
• 2.Ghuman, J., Zunszain, P. A., Petitpas, I., Bhattacharya, A. A., Otagiri, M., & Curry, S. (2005). Structural basis of the drug-binding specificity of human serum albumin.
• 3.Peters Jr, T. (1996). All about albumin: biochemistry, genetics, and medical applications. Academic Press.
• 4.Roche, M., Rondeau, P., & Singh, N. R. (2008). Tarnus E. Bourdon E. The antioxidant properties of serum albumin. FEBS Letters, 582(13), 1783–1787.
• 5.Curry, S. (1995). Lessons from the crystallographic analysis of small molecule binding to human serum albumin. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology, 1247(1), 83–91.
• 6.Vincent, J. L., Russell, J. A., Jacob, M., Martin, G., Guidet, B., Wernerman, J., ... & Wilkes, M. M. (2018). Albumin administration in the acutely ill: what is new and where next? Critical Care, 22(1), 184.
• 7.Kratz, F. (2008). Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. Journal of Controlled Release, 132(3), 171–183.
• 8.Roche, M., Rondeau, P., & Singh, N. R. (2008). The anti-inflammatory properties of HDLs are impaired in acute coronary syndrome but are improved after extended-release niacin treatment. Clinical Science, 116(9), 873–883.
• 9.Selvaraj, P., & Sathiyapriya, V. (2014). Role of human serum albumin in the in vitro glycation of hemoglobin. Journal of Biomolecular Structure and Dynamics, 32(3), 394–404.