alpha-2-HS-glycoprotein (AHSG, Alpha-2-Heremans-Schmid Glycoprotein) also known as fetuin-A is a
protein that in humans is encoded by the ''AHSG''
gene.
Fetuin-A belongs to the
fetuin class of plasma binding proteins and is more abundant in fetal than adult blood.
Function
Alpha2-HS glycoprotein, a
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
present in the serum, is synthesized by
hepatocytes and
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
s.
The AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several functions, such as
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
, brain development and the formation of bone tissue. The protein is commonly present in the
cortical plate of the immature cerebral cortex and bone marrow hemopoietic matrix, and it has therefore been postulated that it participates in the development of the tissues. However, its exact significance is still obscure.
The
choroid plexus is an established extrahepatic expression site. The mature circulating AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. Multiple post-translational modifications have been reported.
Thus AHSG is a secreted partially phosphorylated glycoprotein with complex proteolytic processing that circulates in blood and extracellular fluids. In the test tube AHSG can bind multiple ligands and therefore has been claimed to be involved in several functions, such as endocytosis, brain development and the formation of bone tissue. Most of these functions await confirmation in vivo.
Clinical significance
Fetuins are
carrier proteins like
albumin. Fetuin-A forms soluble complexes with
calcium and
phosphate and thus is a carrier of otherwise insoluble
calcium phosphate.
Thus fetuin-A is a potent inhibitor of pathological calcification, in particular
Calciphylaxis.
Mice deficient in fetuin-A show systemic
calcification of soft tissues.
Fetuin-A can inhibit calcification, and inhibits
osteogenesis in bone.
Fetuin-A appears to promote calcification in
coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
, but oppose calcification in
peripheral artery disease.
High levels of Fetuin-A are associated with obesity and
insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
.
Fetuin-A promotes insulin resistance by enhancing the binding of
free fatty acids to
TLR4.
In
adipose tissue, Fetuin-A
downregulates the
expression of
adiponectin, thereby increasing inflammation and insulin resistance.
Also in adipose tissue, Fetuin-A reduces
lipogenesis
In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synt ...
and increases
lipolysis, thereby increasing obesity and insulin resistance.
Supervised exercise (that is not associated with weight reduction) reduces Fetuin-A.
See also
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Fetuin-B
References
External links
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Further reading
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{{refend
Glycoproteins