Fatty acid transport proteins

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Fatty acid transport proteins (FATPs, SLC27, SLC27A) are a family of trans-membrane transport proteins, which allow and enhance the uptake of long chain fatty acids into cells. [1] This subfamily is part of the solute carrier protein family. Within humans this family contains six very homologous proteins, which are expressed in all tissues of the body which use fatty acids: [2]

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Coenzyme A Coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle

Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).

Beta oxidation Process of fatty acid breakdown

In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.

Acyl carrier protein

The acyl carrier protein (ACP) is an important component in both fatty acid and polyketide biosynthesis with the growing chain bound during synthesis as a thiol ester at the distal thiol of a 4'-phosphopantetheine moiety. The ACPs are related in structure and mechanism to the peptidyl carrier proteins (PCP) from nonribosomal peptide synthases.

Long-chain-fatty-acid—CoA ligase

The long chain fatty acyl-CoA ligase is an enzyme of the ligase family that activates the oxidation of complex fatty acids. Long chain fatty acyl-CoA synthetase catalyzes the formation of fatty acyl-CoA by a two-step process proceeding through an adenylated intermediate. The enzyme catalyzes the following reaction,

Beta-ketoacyl-ACP synthase

In molecular biology, Beta-ketoacyl-ACP synthase EC 2.3.1.41, is an enzyme involved in fatty acid synthesis. It typically uses malonyl-CoA as a carbon source to elongate ACP-bound acyl species, resulting in the formation of ACP-bound β-ketoacyl species such as acetoacetyl-ACP.

In enzymology, a long-chain-fatty-acid-[acyl-carrier-protein] ligase is an enzyme that catalyzes the chemical reaction

Fatty-acyl-CoA synthase

Fatty-acyl-CoA Synthase, or more commonly known as yeast fatty acid synthase, is an enzyme complex responsible for fatty acid biosynthesis, and is of Type I Fatty Acid Synthesis (FAS). Yeast fatty acid synthase plays a pivotal role in fatty acid synthesis. It is a 2.6 MDa barrel shaped complex and is composed of two, unique multi-functional subunits: alpha and beta. Together, the alpha and beta units are arranged in an α6β6 structure. The catalytic activities of this enzyme complex involves a coordination system of enzymatic reactions between the alpha and beta subunits. The enzyme complex therefore consists of six functional centers for fatty acid synthesis.

ACSL1

Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.

ACSL5

Long-chain-fatty-acid—CoA ligase 5 is an enzyme that in humans is encoded by the ACSL5 gene.

Very long-chain acyl-CoA synthetase

Very long-chain acyl-CoA synthetase is an enzyme that in humans is encoded by the SLC27A2 gene.

Long-chain fatty acid transport protein 4

Long-chain fatty acid transport protein 4 is a protein that in humans is encoded by the SLC27A4 gene. This membrane protein is also called FATP4 or ACSVL5. The purified protein shows enzyme activity, esterifying long and very long chain fatty acids with Coenzyme A. It is debated whether it is also a fatty acid transporter at the plasma membrane.

ACSBG1

Acyl-CoA Synthetase, Bubblegum Family, member 1 (ACSBG1) is an enzyme that in humans is encoded by the ACSBG1 gene.

ACOT11

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene. This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.

SLC27A5

Bile acyl-CoA synthetase is an enzyme that in humans is encoded by the SLC27A5 gene.

SLC27A6

Long-chain fatty acid transport protein 6 is a protein that in humans is encoded by the SLC27A6 gene.

Long-chain fatty acid transport protein 1

Long-chain fatty acid transport protein 1 (FATP1) is a protein that in humans is encoded by the SLC27A1 gene.

SLC27A3

Long-chain fatty acid transport protein 3 is a protein that in humans is encoded by the SLC27A3 gene.

Ketoacyl synthase

Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the resulting acyl chain is two carbon atoms longer than before. KSs exist as individual enzymes, as they do in type II fatty acid synthesis and type II polyketide synthesis, or as domains in large multidomain enzymes, such as type I fatty acid synthases (FASs) and polyketide synthases (PKSs). KSs are divided into five families: KS1, KS2, KS3, KS4, and KS5.

ACOT13

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene. This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.

The amino acid-polyamine-organocation (APC) superfamily is the second largest superfamily of secondary carrier proteins currently known, and it contain several Solute carriers. Originally, the APC superfamily consisted of subfamilies under the transporter classification number 2.A.3. This superfamily has since been expanded to include eighteen different families.

References

  1. Houten, Sander Michel; Wanders, Ronald J. A. (October 2010). "A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation". Journal of Inherited Metabolic Disease. 33 (5): 469–477. doi:10.1007/s10545-010-9061-2. ISSN   1573-2665. PMC   2950079 . PMID   20195903.
  2. Doege, Holger; Stahl, Andreas (August 2006). "Protein-mediated fatty acid uptake: novel insights from in vivo models". Physiology. 21 (4): 259–268. doi:10.1152/physiol.00014.2006. ISSN   1548-9213. PMID   16868315.