Apolipoprotein A-IV is plasma protein that is the product of the human 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...

 APOA4.

Gene

APOA4 resides on chromosome 11 in close linkage to APOA1 and APOC3. APOA4 contains 3 exon

Exon

An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s separated by two intron

Intron

An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...

s, and is polymorphic

Polymorphism (biology)

Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...

, although most of the reported sequence polymorphisms occur in exon 3. The best validated and studied non-synonymous SNPs are a glutamine

Glutamine

Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...

 → histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 substitution at codon 360 and a threonine

Threonine

Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

 → serine

Serine

Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

 substitution at codon 347; a sequence polymorphism has also been identified in the 3'UTR of the third exon. Intra-species comparative gene sequence analysis suggests that the APOA4 gene arose from APOA1 by gene duplication approximately 270 MYA.

Function

The primary translation product of the APOA4 gene is a 396-residue preprotein, which undergoes proteolytic processing to yield apo A-IV, a 376-reside mature O-linked glycoprotein. In most mammals, including humans, apo A-IV synthesis is confined to the intestine

Intestine

In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...

; however in mice and rats hepatic synthesis also occurs. Apo A-IV is secreted into circulation on the surface of newly synthesized chylomicron

Chylomicron

Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...

 particles. Intestinal fat absorption dramatically increases the synthesis and secretion of apo A-IV. Although its primary function in human lipid metabolism has not been established, apo A-IV has been found to: 1) activate lecithin-cholesterol acyltransferase

Lecithin-cholesterol acyltransferase

Lecithin-cholesterol acyltransferase is an enzyme that converts free cholesterol into cholesteryl ester , which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become...

 and cholesterylester transfer protein

Cholesterylester transfer protein

Cholesteryl ester transfer protein , also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins...

 in vitro; 2) play a role in the regulation of appetite

Appetite

The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

 and satiety in rodent models; 3) display anti-oxidant and anti-atherogenic

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

 properties in vitro and in rodent models; 4) modulate the efficiency of enterocyte and hepatic transcellular lipid

Lipid

Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

transport in vitro. Human apo A-IV deficiency has not been reported.

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