Alpha-fetoprotein

Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4 (4q25).

AFP is a major plasma protein produced by the yolk sac and the liver during fetal development. It is thought to be the fetal form of serum albumin. AFP binds to copper, nickel, fatty acids and bilirubin and is found in monomeric, dimeric and trimeric forms.

Structure
AFP is a glycoprotein of 591 amino acids and a carbohydrate moiety.

Function
AFP is the most abundant plasma protein found in the human fetus. Plasma levels decrease rapidly after birth but begin decreasing prenatally starting at the end of the first trimester. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adults is unknown; however, in rodent fetuses it binds estradiol to prevent the transport of this hormone across the placenta. The main function of this is to prevent the masculinization of female fetuses. As human AFP does not bind estrogen, its function in human fetuses is less clear.

The rodent AFP system can be overridden with massive injections of estrogen, which swamp the AFP system and will masculinize the fetus. The masculinizing effect of estrogens may seem counter-intuitive since estrogens are critical for the proper development of female secondary characteristics during puberty. However, this is not the case prenatally. Gonadal hormones from the testes, such as testosterone and antimullerian hormone are required to cause development of a phenotypic male. Without these hormones the fetus will develop into a phenotypic female even if genetically XY. Interestingly, the conversion of testosterone into estradiol by aromatase in many tissues may be an important step in masculinization of that tissue. Masculinization of the brain is thought to occur both by conversion of testosterone into estradiol by aromatase, but also by de novo synthesis of estrogens within the brain. Thus, AFP may protect the fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus, but its exact role is still controversial.

Maternal
In pregnant women, fetal AFP levels can be monitored in urine. AFP is cleared strongly from the kidneys allowing AFP to tend to mirror fetal serum levels. In contrast, maternal serum AFP levels are much lower but continue to rise until about week 32. This is thought to be because the mother is not utilising the AFP, and therefore clears it from her system without issue.

Infants
The normal range of AFP for adults and children is variously reported as under 50, under 10, and under 5 ng/mL. At birth, normal infants have AFP levels 4 or more orders of magnitude above this normal range, that decreases to a normal range over the first year of life.

During this time, the normal range of AFP levels spans approximately 2 orders of magnitude. Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns.

Very high AFP levels may be subject to hooking (see Tumor marker), which results in the level being reported significantly lower than the actual concentration. This is important for analysis of a series of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer survivors, where the rate of decrease of AFP has diagnostic value.

Clinical significance
AFP is measured in pregnant women through the analysis of maternal blood or amniotic fluid, as a screening test for a subset of developmental abnormalities. Some of the diseases in which AFP will be elevated in a person are listed below:
 * Omphalocele
 * Down Syndrome (decrease)
 * Hepatocellular carcinoma/hepatoma: ↑ α-fetoprotein
 * Neural tube defects: ↑ α-fetoprotein in amniotic fluid and maternal serum
 * Nonseminomatous germ cell tumors
 * Yolk sac tumor
 * Ataxia telangectasia: Elevation of AFP is used as one factor in the diagnosis of ataxia telangiectasia.
 * Tumors: AFP can also be used as a biomarker to detect a subset of tumors in non-pregnant women, men, and children. A level above 500 nanograms/milliliter of AFP in adults can be indicative of hepatocellular carcinoma, germ cell tumors, and metastatic cancers of the liver.

A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties.