Alpha-1-microglobulin (A1M, α1-microglobulin,B. Ekström, P.A. Peterson, I. Berggård "A urinary and plasma alpha-1-glycoprotein of low molecular weight: isolation and some properties." ''Biochem. Biophys. Res. Commun'' 1975, vol. sometimes also called Protein HC) is a

microglobulin Microglobulin is a globulin of relatively small molecular weight. It can be contrasted to macroglobulin., Examples include: * Beta-2 microglobulin * Alpha-1-microglobulin Alpha-1-microglobulin (A1M, α1-microglobulin,B. Ekström, P.A. Peterson, I. ...

, a small globular protein. It is found in all vertebrates, including humans, and is distributed in

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the ...

and extravascular tissues of all organs. It is synthesized in most cells of the body, but mainly in the liverAlpha-1-microglobulin: Innate defence against pathological oxidation
by Magnus G Olsson, 2009 from a gene that codes for the alpha-1-microglobulin/bikunin precursor.

Structure

Human A1M is composed of a 183-amino-acid peptide carrying three carbohydrate chains. It belongs to a protein family, the

lipocalin The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids and most lipocalins are also able to bind to complexed iron (via siderophores or flavonoids) as well as heme. The ...

s, all members of which are shaped as a basket built from eight beta-strands of the peptide chain. A cysteine residue on one of the loops at the open end of the basket is of central importance for the function.

Function

A1M binds and degrades

heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...

, is a radical scavenger as well as a reductase. A model has been proposed in which A1M is described as a circulating “waste bin” which continuously removes free radicals and oxidizing agents, particularly heme, from the tissues. It is subsequently transported to the kidneys, where it is broken down. The protein is therefore believed to protect cells and tissues against the damage that is induced by abnormally high concentrations of free hemoglobin and/or

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ...

(also called “

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal re ...

”). A1M is also immunoregulatory: the immune response of lymphocytes and neutrophils is partly suppressed by A1M.

Role in diagnosis

A1M can be used as an indicator of

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...

. The test can be regarded as positive when the ratio of A1M (in

milligram The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially ...

s) and creatinine in

millimoles The mole, symbol mol, is the unit of amount of substance in the International System of Units (SI). The quantity amount of substance is a measure of how many elementary entities of a given substance are in an object or sample. The mole is define ...

in the urine is over 0.7 mg/mmol. A test for

preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...

, where A1M serves as the diagnostic marker, has been proposed. It is based upon the fact that oxidative stress in the placenta tissue triggers the endogenous synthesis and plasma concentration of the protein.

Therapeutic potential

A1M is a candidate for a number of therapeutic applications which includes the treatment or alleviation of preeclampsia, tissue damage caused by bleeding in brain, and chronic leg ulcers.

References

{{reflist Lipocalins