Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''AFP''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The ''AFP'' gene is located on the ''q'' arm of

chromosome 4 Chromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 190 million base pairs (the building material of DNA) and represents between 6 and 6.5 percent of the to ...

(4q13.3). Maternal AFP serum level is used to screen for Down syndrome,

neural tube defect Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo ...

s, and other chromosomal abnormalities. AFP is a major

plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

produced by the

yolk sac The yolk sac is a membranous wikt:sac, sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac' ...

and the fetal liver during fetal development. It is thought to be the fetal analog of

serum albumin Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chem ...

. AFP binds to copper,

nickel Nickel is a chemical element; it has symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive, but large pieces are slo ...

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

s and

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

and is found in

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

ic, dimeric and trimeric forms.

Structure

AFP is a

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...

of 591 amino acids and a carbohydrate moiety.

Function

The function of AFP in adult humans is unknown. AFP is the most abundant plasma protein found in the human fetus. In the fetus, AFP is produced by both the liver and the yolk sac. It is believed to function as a carrier protein (similar to albumin) that transports materials such as fatty acids to cells. Maternal plasma levels peak near the end of the first trimester, and begin decreasing prenatally at that time, then decrease rapidly after birth. Normal adult levels in the newborn are usually reached by the age of 8 to 12 months. While the function in humans is unknown, in rodents it binds

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

to prevent the transport of this hormone across the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

to the fetus. The main function of this is to prevent the

virilization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is a medical term commonly used in three medical a ...

of female fetuses. As human AFP does not bind estrogen, its function in humans is less clear. In human liver cancer, AFP is found to bind glypican-3 (GPC3), another oncofetal antigen. The rodent AFP system can be overridden with massive injections of estrogen, which overwhelm 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 Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

and

anti-Müllerian hormone Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to Activin and inhibin, inhibin and activin from the transforming growth factor beta superfamily, whose key roles a ...

, are required to cause development of a phenotypic male. Without these hormones, the fetus will develop into a phenotypic female even if genetically XY. The conversion of testosterone into estradiol by

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze man ...

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 In chemistry, ''de novo'' synthesis () is the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can ...

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.

Serum levels

Maternal

In pregnant women, fetal AFP levels can be monitored in the urine of the pregnant woman. Since AFP is quickly cleared from the mother's serum via her kidneys, maternal urine AFP correlates with fetal serum levels, although the maternal urine level is much lower than the fetal serum level. AFP levels rise until about week 32. Maternal serum alpha-fetoprotein (MSAFP) screening is performed at 16 to 18 weeks of gestation. If MSAFP levels indicate an anomaly,

amniocentesis Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ...

may be offered to the patient.

Infants

The normal range of AFP for adults and children is variously reported as under 50, under 10, or under 5 ng/mL. At birth, normal infants have AFP levels four 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 two 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 A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, s ...

), 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

Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

amniotic fluid The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...

as a

screening test In medicine, screening is a strategy used to look for as-yet-unrecognised conditions or risk markers. This testing can be applied to individuals or to a whole population without symptoms or signs of the disease being screened. Screening interv ...

for certain developmental abnormalities, such as

aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell (biology), cell, for example a human somatic (biology), somatic cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more plo ...

. Second, serum AFP level is elevated in people with certain tumors, and so it is used as a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

to follow these diseases. Some of these diseases are listed below: * ''Developmental birth defects associated with elevated AFP'' **

Omphalocele An omphalocele or omphalocoele, also known as an exomphalos, is a rare abdominal wall defect. Beginning at the 6th week of development, rapid elongation of the gut and increased liver size reduces intra abdominal space, which pushes intestinal lo ...

Gastroschisis Gastroschisis is a birth defect in which the baby's intestines extend outside of the abdomen through a hole next to the belly button. The size of the hole is variable, and other organs including the stomach and liver may also occur outside the b ...

Neural tube defect Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo ...

s: ↑ α-fetoprotein in amniotic fluid and maternal serum * ''Tumors associated with elevated AFP'' **

Hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

Le, Tao. First Aid for the USMLE Step 1 2013. New York: McGraw-Hill Medical, 2013. Print. ** Metastatic disease affecting the liver ** Nonseminomatous

germ cell tumor A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary and testis), but can arise in other areas of the body. Extragon ...

s ** Yolk sac tumor * ''Other conditions associated with elevated AFP'' ** Ataxia telangiectasia: elevated AFP is used as one factor in diagnosis A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties. In the treatment of

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...

it is paramount to differentiate seminomatous and nonseminomatous tumors. This is typically done pathologically after removal of the testicle and confirmed by tumor markers. However, if the pathology is pure

seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a Malignancy, malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if di ...

but the AFP is elevated, the tumor is treated as a nonseminomatous tumor because it contains yolk sac (nonseminomatous) components.

References

External links

* * {{NLM content Glycoproteins Tumor markers Obstetrics Midwifery