Carnitine-acylcarnitine translocase

Last updated
SLC25A20
Identifiers
Aliases SLC25A20 , CAC, CACT, Carnitine-acylcarnitine translocase, solute carrier family 25 member 20
External IDs OMIM: 613698 MGI: 1928738 HomoloGene: 331 GeneCards: SLC25A20
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000387

NM_020520

RefSeq (protein)

NP_000378

NP_065266

Location (UCSC) Chr 3: 48.86 – 48.9 Mb Chr 9: 108.54 – 108.56 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
solute carrier family 25 (carnitine/acylcarnitine translocase), member 20
Identifiers
SymbolSLC25A20
Alt. symbolsCACT
NCBI gene 788
HGNC 1421
OMIM 212138
RefSeq NM_000387
UniProt O43772
Other data
Locus Chr. 3 p21.31
Search for
Structures Swiss-model
Domains InterPro

Carnitine-acylcarnitine translocase (CACT) is responsible for passive transport of carnitine and carnitine-fatty acid complexes and across the inner mitochondrial membrane as part of the carnitine shuttle system.

Contents

Function

Fatty acyl–carnitine can diffuse from the cytosol across the porous outer mitochondrial membrane to the intermembrane space, but must utilize CACT to cross the nonporous inner mitochondrial membrane and reach the mitochondrial matrix. CACT is a cotransporter, returning one molecule of carnitine from the matrix to the intermembrane space as one molecule of fatty acyl–carnitine moves into the matrix. [5]

Clinical significance

A disorder is associated with carnitine-acylcarnitine translocase deficiency. This disorder disrupts the carnitine shuttle system from moving fatty acids across the mitochondrial membrane, leading to a decrease in fatty acid catabolism. The result is an accumulation of fatty acid within muscles and liver, decreased tolerance to long term exercise, inability to fast for more than a few hours, muscle weakness and wasting, and a strong acidic smell on the breath (due to protein catabolism).

Acyl-CoA from cytosol to the mitochondrial matrix Acyl-CoA from cytosol to the mitochondrial matrix.svg
Acyl-CoA from cytosol to the mitochondrial matrix

Related Research Articles

<span class="mw-page-title-main">Carnitine</span> Amino acid active in mitochondria

Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for free energy production, and also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo.

Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.

<span class="mw-page-title-main">Intermembrane space</span>

The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. It also refers to the space between the inner and outer nuclear membranes of the nuclear envelope, but is often called the perinuclear space. The IMS of mitochondria plays a crucial role in coordinating a variety of cellular activities, such as regulation of respiration and metabolic functions. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function.

<span class="mw-page-title-main">Beta oxidation</span> Process of fatty acid breakdown

In biochemistry and metabolism, beta oxidation (also β-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.

<span class="mw-page-title-main">Inborn error of lipid metabolism</span> Medical condition

Numerous genetic disorders are caused by errors in fatty acid metabolism. These disorders may be described as fatty oxidation disorders or as a lipid storage disorders, and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types.

<span class="mw-page-title-main">Carnitine palmitoyltransferase II deficiency</span> Medical condition

Carnitine palmitoyltransferase II deficiency, sometimes shortened to CPT-II or CPT2, is an autosomal recessively inherited genetic metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. The disorder presents in one of three clinical forms: lethal neonatal, severe infantile hepatocardiomuscular and myopathic.

<span class="mw-page-title-main">Carnitine-acylcarnitine translocase deficiency</span> Medical condition

Carnitine-acylcarnitine translocase deficiency is a rare, autosomal recessive metabolic disorder that prevents the body from converting long-chain fatty acids into energy, particularly during periods without food. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty enzyme that prevents long-chain fatty acids from being transported into the innermost part of the mitochondria for processing.

<span class="mw-page-title-main">ACADVL</span> Protein-coding gene in the species Homo sapiens

Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (VLCAD) is an enzyme that in humans is encoded by the ACADVL gene.

<span class="mw-page-title-main">Inner mitochondrial membrane</span>

The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.

<span class="mw-page-title-main">Palmitoylcarnitine</span> Chemical compound

Palmitoylcarnitine is an ester derivative of carnitine involved in the metabolism of fatty acids. During the tricarboxylic acid cycle (TCA), fatty acids undergo a process known as β-oxidation to produce energy in the form of ATP. β-oxidation occurs primarily within mitochondria, however the mitochondrial membrane prevents the entry of long chain fatty acids (>C10), so the conversion of fatty acids such as palmitic acid is key. Palmitic acid is brought to the cell and once inside the cytoplasm is first converted to Palmitoyl-CoA. Palmitoyl-CoA has the ability to freely pass the outer mitochondrial membrane, but the inner membrane is impermeable to the Acyl-CoA and thioester forms of various long-chain fatty acids such as palmitic acid. The palmitoyl-CoA is then enzymatically transformed into palmitoylcarnitine via the Carnitine O-palmitoyltransferase family. The palmitoylcarnitine is then actively transferred into the inner membrane of the mitochondria via the carnitine-acylcarnitine translocase. Once inside the inner mitochondrial membrane, the same Carnitine O-palmitoyltransferase family is then responsible for transforming the palmitoylcarnitine back to the palmitoyl-CoA form.

Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, in the end generating acetyl-CoA, the entry molecule for the citric acid cycle, the main energy supply of living organisms, including bacteria and animals. It includes three major steps:

<span class="mw-page-title-main">Carnitine palmitoyltransferase I</span> Protein-coding gene in the species Homo sapiens

Carnitine palmitoyltransferase I (CPT1) also known as carnitine acyltransferase I, CPTI, CAT1, CoA:carnitine acyl transferase (CCAT), or palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine. The product is often Palmitoylcarnitine, but other fatty acids may also be substrates. It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria.

Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.

<span class="mw-page-title-main">TIMM8A</span> Protein-coding gene in humans

Mitochondrial import inner membrane translocase subunit Tim8 A, also known as deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the TIMM8A gene. This translocase has similarity to yeast mitochondrial proteins that are involved in the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in deafness-dystonia syndrome and it is postulated that MTS/DFN-1 is a mitochondrial disease caused by a defective mitochondrial protein import system.

<span class="mw-page-title-main">ETFDH</span> Protein-coding gene in humans

Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial is an enzyme that in humans is encoded by the ETFDH gene. This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain.

<span class="mw-page-title-main">TIMM50</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit TIM50 is a protein that in humans is encoded by the TIMM50 gene. Tim50 is a subunit of the Tim23 translocase complex in the inner mitochondrial membrane. Mutations in TIMM50 can lead to epilepsy, severe intellectual disability, and 3-methylglutaconic aciduria. TIMM50 expression is increased in breast cancer cells and decreased in hypertrophic hearts.

<span class="mw-page-title-main">Fatty-acid metabolism disorder</span> Medical condition

A broad classification for genetic disorders that result from an inability of the body to produce or utilize an enzyme or transport protein that is required to oxidize fatty acids. They are an inborn error of lipid metabolism, and when it affects the muscles also a metabolic myopathy.

<span class="mw-page-title-main">PAM16</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit TIM16 also known as presequence translocated-associated motor subunit PAM16, mitochondria-associated granulocyte macrophage CSF-signaling molecule, or presequence translocated-associated motor subunit PAM16 is a protein that in humans is encoded by the PAM16 gene.

<span class="mw-page-title-main">IMMP2L</span> Protein-coding gene in the species Homo sapiens

Inner mitochondrial membrane peptidase subunit 2 (IMMP2L) is an enzyme that in humans is encoded by the IMMP2L gene on chromosome 7. This protein catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the intermembrane space. IMMP2L processes the nuclear encoded protein DIABLO.

<span class="mw-page-title-main">Citrate–malate shuttle</span>

The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000178537 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032602 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Principles of biochemistry, 2nd edition, edited by Albert Lehninger, David Nelson, and Michael Cox, Worth Publishers, Inc., New York, 1992, 1012 pp, $67.95". Molecular Reproduction and Development. 37 (4): 477. April 1994. doi:10.1002/mrd.1080370421. ISSN   1040-452X.