Alpha-fetoprotein
Encyclopedia
Alpha-fetoprotein is a protein
that in humans is encoded by the AFP gene
.
AFP is a major plasma protein produced by the yolk sac and the liver during fetal development that is thought to be the fetal form of serum albumin
. The AFP gene
is located on the q arm of chromosome 4 (4q25). AFP binds to copper, nickel, fatty acid
s and bilirubin
and is found in monomeric, dimeric and trimeric forms.
The human fetus has the highest amount of AFP levels found in humans. At the end of the first trimester, fetal AFP levels decrease. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adults is unknown; however, in fetuses it binds estradiol
to prevent the transport of this hormone across the placenta. 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: it is principally increased in open neural tube defects
and omphalocele
& decreased in Down syndrome
. It 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 tumor
s, and metastatic cancers of the liver.
In rats, AFP binds maternal estrogen, preventing its passage through the placenta. The main function of this is to prevent the masculinization of female fetuses. The system can be overridden with massive injections of estrogen, which swamp the AFP system and masculinize female fetuses.
of 591 amino acids and a carbohydrate moiety. Many functions have been proposed for AFP such as an anti-cancer active site peptide has been identified and is referred to as AFPep
. 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.
, a large US
clinical laboratory testing company, began offering AFP screening tests in the early 1980s.
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
), resulting in a reported high level that is nonetheless significantly lower than the actual level. 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the AFP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
AFP is a major plasma protein produced by the yolk sac and the liver during fetal development that is thought to be the fetal form of serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
. The AFP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
is located on the q arm of chromosome 4 (4q25). AFP binds to copper, nickel, fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s and bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
and is found in monomeric, dimeric and trimeric forms.
The human fetus has the highest amount of AFP levels found in humans. At the end of the first trimester, fetal AFP levels decrease. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adults is unknown; however, in fetuses it binds estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
to prevent the transport of this hormone across the placenta. AFP is measured in pregnant women through the analysis of maternal blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
or amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
, as a screening test for a subset of developmental abnormalities: it is principally increased in open neural tube defects
Neural tube defects
Neural tube defects are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 2nd week of pregnancy called gastrulation, specialized cells...
and omphalocele
Omphalocele
An omphalocele is a type of abdominal wall defect in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall.-Presentation:The sac, which is formed from an outpouching of...
& decreased in Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
. It 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
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
, germ cell tumor
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...
s, and metastatic cancers of the liver.
In rats, AFP binds maternal estrogen, preventing its passage through the placenta. The main function of this is to prevent the masculinization of female fetuses. The system can be overridden with massive injections of estrogen, which swamp the AFP system and masculinize female fetuses.
Structure and levels
AFP is a glycoproteinGlycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
of 591 amino acids and a carbohydrate moiety. Many functions have been proposed for AFP such as an anti-cancer active site peptide has been identified and is referred to as AFPep
AFPep
AFPep is an orally active cyclic peptide with molecular weight of 969 Daltons and is derived from the anti-oncogenic active site of alpha fetoprotein . Using the standard amino acid abbreviations, AFPep has the sequence cyclo-, where O is hydroxyproline...
. 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.
History
LabCorpLabCorp
Laboratory Corporation of America Holdings , more commonly known as LabCorp, is an S&P 500 company headquartered in Burlington, North Carolina. It operates one of the largest clinical laboratory networks in the world, with a United States network of 36 primary laboratories. Before a merger with...
, a large US
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
clinical laboratory testing company, began offering AFP screening tests in the early 1980s.
AFP in normal 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 magnitudeOrder of magnitude
An order of magnitude is the class of scale or magnitude of any amount, where each class contains values of a fixed ratio to the class preceding it. In its most common usage, the amount being scaled is 10 and the scale is the exponent being applied to this amount...
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
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...
), resulting in a reported high level that is nonetheless significantly lower than the actual level. 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.