Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Abstract

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Keywords: advanced glycation end products; albumin; endothelium; esterases; glycocalyx; oxidative stress; pathogenesis; transcytosis; transport.

Figure 1

The main sites of HSA modification. The sites of in vivo glycation are shown in red (lysines) and blue (arginines). The site of redox modification (Cys34) is shown in yellow. To create the figure, a crystal structure of HSA from the PDB database (code 3JQZ [24]) was used.

Figure 2

Structures of Sudlow site I of HSA (A), BSA (B) and RSA (C).

Figure 3

Structures of Sudlow site II of of HSA (A), BSA (B) and RSA (C).

Figure 4

Structures of the redox sites of HSA (A), BSA (B) and RSA (C).

Figure 5

Interaction of glycated albumin with endothelial cells (EC). AP-1, activator protein 1; BNB, blood–nerve barrier; DN, diabetic nephropathy; DPN, diabetic peripheral neuropathy; eNOS, endothelial nitric oxide synthase; GA, glycated albumin; HAS, hyaluronic acid synthase; HPSE, heparanase; HYAL, hyaluronidases; JAK/STAT, Janus kinase signal transducer and activator of transcription; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MMPs, matrix metalloproteinase; NEU, neu raminidase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NOX, NADPH oxidase; p21ras, products of the ras (rat sarcoma virus) gene family; Pho GTPase, Rho family of GTPases; PI3K, phosphoinositide 3-kinase; PNS, peripheral nervous system; PXDN, Peroxidasin; RAGE, receptor for advanced glycation endproducts; SOD, Superoxide dismutase; VEGF, vascular endothelial growth factor.

Figure 6

Albumin and endothelial glycocalyx layer (EGL). The EGL serves as the “exclusion zone” or “gap” between endothelium and blood cells. The layer also acts as a filter, limiting the passage of molecules larger than 70 kDa. Albumin, with a molecular weight of about 66 kDa, can firmly bind to the EGL and penetrate into the interstitium by transcytosis.