Carnitine

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Carnitine
Carnitine.svg
Carnitine-3D-structure.png
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Routes of
administration 		Oral, intravenous
ATC code
  • A16AA01 ( WHO )(l-form)
Legal status
Legal status
Pharmacokinetic data
Bioavailability <10%
Protein binding None
Metabolism slightly [ clarification needed ]
Excretion Urine (>95%)
Identifiers
  • 3-hydroxy-4-(trimethylazaniumyl)butanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.343 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C7H15NO3
Molar mass 161.201 g·mol−1
3D model (JSmol)
  • C[N+](C)(C)CC(CC(=O)[O-])O
  • InChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3 Yes check.svgY
  • Key:PHIQHXFUZVPYII-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. [1] [2] [3] [4] 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. [3] Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. [3] Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo. [1]

Contents

Carnitine exists as one of two stereoisomers: the two enantiomers d-carnitine (S-(+)-) and l-carnitine (R-(−)-). [5] Both are biologically active, but only l-carnitine naturally occurs in animals, and d-carnitine is toxic as it inhibits the activity of the l-form. [6] At room temperature, pure carnitine is a whiteish powder, and a water-soluble zwitterion with relatively low toxicity. Derived from amino acids, [7] carnitine was first extracted from meat extracts in 1905, leading to its name from Latin, "caro/carnis" or flesh. [2]

Some individuals with genetic or medical disorders (such as preterm infants) cannot make enough carnitine, requiring dietary supplementation. [1] [3] [4] Despite common carnitine supplement consumption among athletes for improved exercise performance or recovery, there is insufficient high-quality clinical evidence to indicate it provides any benefit. [3] [4]

Biosynthesis and metabolism

Carnitine biosynthesis Biosynthesis L-carnitine.pdf
Carnitine biosynthesis

Many eukaryotes have the ability to synthesize carnitine, including humans. [1] [3] Humans synthesize carnitine from the substrate TML (6-N-trimethyllysine), which is in turn derived from the methylation of the amino acid lysine. [1] TML is then hydroxylated into hydroxytrimethyllysine (HTML) by trimethyllysine dioxygenase (TMLD), requiring the presence of ascorbic acid and iron. HTML is then cleaved by HTML aldolase (HTMLA, a pyridoxal phosphate requiring enzyme), yielding 4-trimethylaminobutyraldehyde (TMABA) and glycine. TMABA is then dehydrogenated into gamma-butyrobetaine in an NAD+-dependent reaction, catalyzed by TMABA dehydrogenase. [1] Gamma-butyrobetaine is then hydroxylated by gamma butyrobetaine hydroxylase (a zinc binding enzyme [8] ) into l-carnitine, requiring iron in the form of Fe2+. [1] [9]

Carnitine is involved in transporting fatty acids across the mitochondrial membrane, by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase I and carnitine palmitoyltransferase II. [10] Carnitine also plays a role in stabilizing acetyl-CoA and coenzyme A levels through the ability to receive or give an acetyl group. [1]

Tissue distribution of carnitine-biosynthetic enzymes

The tissue distribution of carnitine-biosynthetic enzymes in humans indicates TMLD to be active in the liver, heart, muscle, brain and highest in the kidneys. [1] HTMLA activity is found primarily in the liver. The rate of TMABA oxidation is greatest in the liver, with considerable activity also in the kidneys. [1]

Carnitine shuttle system

The free-floating fatty acids, released from adipose tissues to the blood, bind to carrier protein molecule known as serum albumin that carry the fatty acids to the cytoplasm of target cells such as the heart, skeletal muscle, and other tissue cells, where they are used for fuel. But before the target cells can use the fatty acids for ATP production and β oxidation, the fatty acids with chain lengths of 14 or more carbons must be activated and subsequently transported into mitochondrial matrix of the cells in three enzymatic reactions of the carnitine shuttle. [11]

The first reaction of the carnitine shuttle is a two-step process catalyzed by a family of isozymes of acyl-CoA synthetase that are found in the outer mitochondrial membrane, where they promote the activation of fatty acids by forming a thioester bond between the fatty acid carboxyl group and the thiol group of coenzyme A to yield a fatty acyl–CoA. [11]

In the first step of the reaction, acyl-CoA synthetase catalyzes the transfer of adenosine monophosphate group (AMP) from an ATP molecule onto the fatty acid generating a fatty acyl–adenylate intermediate and a pyrophosphate group (PPi). The pyrophosphate, formed from the hydrolysis of the two high-energy bonds in ATP, is immediately hydrolyzed to two molecules of Pi by inorganic pyrophosphatase. This reaction is highly exergonic which drives the activation reaction forward and makes it more favorable. In the second step, the thiol group of a cytosolic coenzyme A attacks the acyl-adenylate, displacing AMP to form thioester fatty acyl-CoA. [11]

In the second reaction, acyl-CoA is transiently attached to the hydroxyl group of carnitine to form fatty acylcarnitine. This transesterification is catalyzed by an enzyme found in the outer membrane of the mitochondria known as carnitine acyltransferase 1 (also called carnitine palmitoyltransferase 1, CPT1). [11]

The fatty acylcarnitine ester formed then diffuses across the intermembrane space and enters the matrix by facilitated diffusion through carnitine-acylcarnitine translocase (CACT) located on the inner mitochondrial membrane. This antiporter returns one molecule of carnitine from the matrix to the intermembrane space for every one molecule of fatty acyl–carnitine that moves into the matrix. [11]

In the third and final reaction of the carnitine shuttle, the fatty acyl group is transferred from fatty acyl-carnitine to coenzyme A, regenerating fatty acyl–CoA and a free carnitine molecule. This reaction takes place in the mitochondrial matrix and is catalyzed by carnitine acyltransferase 2 (also called carnitine palmitoyltransferase 2, CPT2), which is located on the inner face of the inner mitochondrial membrane. The carnitine molecule formed is then shuttled back into the intermembrane space by the same cotransporter (CACT) while the fatty acyl-CoA enters β-oxidation. [11]

Regulation of fatty acid β oxidation

The carnitine-mediated entry process is a rate-limiting factor for fatty acid oxidation and is an important point of regulation. [11]

Inhibition

The liver starts actively making triglycerides from excess glucose when it is supplied with glucose that cannot be oxidized or stored as glycogen. This increases the concentration of malonyl-CoA, the first intermediate in fatty acid synthesis, leading to the inhibition of carnitine acyltransferase 1, thereby preventing fatty acid entry into the mitochondrial matrix for β oxidation. This inhibition prevents fatty acid breakdown while synthesis occurs. [11]

Activation

Carnitine shuttle activation occurs due to a need for fatty acid oxidation which is required for energy production. During vigorous muscle contraction or during fasting, ATP concentration decreases and AMP concentration increases leading to the activation of AMP-activated protein kinase (AMPK). AMPK phosphorylates acetyl-CoA carboxylase, which normally catalyzes malonyl-CoA synthesis. This phosphorylation inhibits acetyl-CoA carboxylase, which in turn lowers the concentration of malonyl-CoA. Lower levels of malonyl-CoA disinhibit carnitine acyltransferase 1, allowing fatty acid import to the mitochondria, ultimately replenishing the supply of ATP. [11]

Transcription factors

Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that functions as a transcription factor. It acts in muscle, adipose tissue, and liver to turn on a set of genes essential for fatty acid oxidation, including the fatty acid transporters carnitine acyltransferases 1 and 2, the fatty acyl–CoA dehydrogenases for short, medium, long, and very long acyl chains, and related enzymes. [11]

PPARα functions as a transcription factor in two cases; as mentioned before when there is an increased demand for energy from fat catabolism, such as during a fast between meals or long-term starvation. Besides that, the transition from fetal to neonatal metabolism in the heart. In the fetus, fuel sources in the heart muscle are glucose and lactate, but in the neonatal heart, fatty acids are the main fuel that require the PPARα to be activated so it is able in turn to activate the genes essential for fatty acid metabolism in this stage. [11]

Metabolic defects of fatty acid oxidation

More than 20 human genetic defects in fatty acid transport or oxidation have been identified. In case of fatty acid oxidation defects, acyl-carnitines accumulate in mitochondria and are transferred into the cytosol, and then into the blood. Plasma levels of acylcarnitine in newborn infants can be detected in a small blood sample by tandem mass spectrometry. [11]

When β oxidation is defective because of either mutation or deficiency in carnitine, the ω (omega) oxidation of fatty acids becomes more important in mammals. The ω oxidation of fatty acids is another pathway for F-A degradation in some species of vertebrates and mammals that occurs in the endoplasmic reticulum of the liver and kidney, it is the oxidation of the ω carbon—the carbon farthest from the carboxyl group (in contrast to oxidation which occurs at the carboxyl end of fatty acid, in the mitochondria). [1] [11]

Physiological effects

As an example of normal synthesis, a 70-kilogram (150 lb) person would produce 11–34 mg of carnitine per day. [1] Adults eating mixed diets of red meat and other animal products ingest some 60–180 mg of carnitine per day, while vegans consume about 10–12 mg per day. [3] Most (54–86%) carnitine obtained from the diet is absorbed in the small intestine before entering the blood. [3] The total body content of carnitine is about 20 grams (0.71 oz) in a person weighing 70 kilograms (150 lb), with nearly all of it contained within skeletal muscle cells. [3] Carnitine metabolizes at rates of about 400 μmol (65mg) per day, an amount less than 1% of total body stores. [1]

Deficiency

Carnitine deficiency is rare in healthy people without metabolic disorders, indicating that most people have normal, adequate levels of carnitine normally produced through fatty acid metabolism. [1] One study found that vegans showed no signs of carnitine deficiency. [12] Infants, especially premature infants, have low stores of carnitine, necessitating use of carnitine-fortified infant formulas as a replacement for breast milk, if necessary. [1]

Two types of carnitine deficiency states exist. Primary carnitine deficiency is a genetic disorder of the cellular carnitine-transporter system that typically appears by the age of five with symptoms of cardiomyopathy, skeletal-muscle weakness, and hypoglycemia. [1] [3] Secondary carnitine deficiencies may happen as the result of certain disorders, such as chronic kidney failure, or under conditions that reduce carnitine absorption or increase its excretion, such as the use of antibiotics, malnutrition, and poor absorption following digestion. [1] [3]

Supplementation

Despite widespread interest among athletes to use carnitine for improvement of exercise performance, inhibit muscle cramps, or enhance recovery from physical training, the quality of research for these possible benefits has been low, prohibiting any conclusion of effect. [1] [3] Despite some studies suggest that carnitine may improve high-intensity physical performance, [13] and facilitate recovery after such performance, [14] the results of these studies are inconclusive, since various studies used various regimens of carnitine supplementation and intensity of exercise. [15] [16] At supplement amounts of 2–6 grams (0.071–0.212 oz) per day over a month, there was no consistent evidence that carnitine affected exercise or physical performance on moderate-intensity exercises, whereas on high-intensity exercises results were mixed. [3] Carnitine supplements does not seem to improve oxygen consumption or metabolic functions when exercising, nor do they increase the amount of carnitine in muscle. [1] [3] The underlying mechanisms on how carnitine can improve physical performance, if at all, are not clearly understood. [17] There is no evidence that L-carnitine influences fat metabolism or aids in weight loss. [3] [18] [19]

Male fertility

The carnitine content of seminal fluid is directly related to sperm count and motility, suggesting that the compound might be of value in treating male infertility. [1]

Diseases

Carnitine has been studied in various cardiometabolic conditions, indicating it is under preliminary research for its potential as an adjunct in heart disease and diabetes, among numerous other disorders. [1] Carnitine has no effect on preventing all-cause mortality associated with cardiovascular diseases, [20] and has no significant effect on blood lipids. [1] [21]

Although there is some evidence from meta-analyses that L-carnitine supplementation improved cardiac function in people with heart failure, there is insufficient research to determine its overall efficacy in lowering the risk or treating cardiovascular diseases. [1] [20]

There is only preliminary clinical research to indicate the use of L-carnitine supplementation for improving symptoms of type 2 diabetes, such as improving glucose tolerance or lowering fasting levels of blood glucose. [1] [22]

The kidneys contribute to overall homeostasis in the body, including carnitine levels. In the case of renal impairment, urinary elimination of carnitine increasing, endogenous synthesis decreasing, and poor nutrition as a result of disease-induced anorexia can result in carnitine deficiency. [1] Carnitine has no effect on most parameters in end-stage kidney disease, although it may lower C-reactive protein, a biomarker for systemic inflammation. [23] Carnitine blood levels and muscle stores can become low, which may contribute to anemia, muscle weakness, fatigue, altered levels of blood fats, and heart disorders. [1] Some studies have shown that supplementation of high doses of l-carnitine (often injected) may aid in anemia management. [1]

Sources

The form present in the body is l-carnitine, which is also the form present in food. Food sources rich in l-carnitine are animal products, particularly beef and pork. [1] Red meats tend to have higher levels of l-carnitine. [1] [21] Adults eating diverse diets that contain animal products attain about 23-135 mg of carnitine per day. [1] [24] Vegans get noticeably less (about 10–12 mg) since their diets lack these carnitine-rich animal-derived foods. Approximately 54% to 86% of dietary carnitine is absorbed in the small intestine, then enters the blood. [1] Even carnitine-poor diets have little effect on total carnitine content, as the kidneys conserve carnitine. [21]

Selected food sources of carnitine [1]
FoodMilligrams (mg)
Beef steak, cooked, 4 ounces (110 g)56–162
Ground beef, cooked, 4 ounces (110 g)87–99
Milk, whole, 1 cup (237 g)8
Codfish, cooked, 4 ounces (110 g)4–7
Chicken breast, cooked, 4 ounces (110 g)3–5
Ice cream, 1⁄2 cup (125 mL)3
Cheese, cheddar, 2 ounces (57 g)2
Whole–wheat bread, 2 slices0.2
Asparagus, cooked, 1⁄2 cup (62 g)0.1

In general, omnivorous humans each day consume between 2 and 12  μmol/kg of body weight, accounting for 75% of carnitine in the body. Humans endogenously produce 1.2 μmol/kg of body weight of carnitine on a daily basis, accounting for 25% of the carnitine in the body. [1] [3] Strict vegetarians obtain little carnitine from dietary sources (0.1 μmol/kg of body weight daily), as it is mainly found in animal-derived foods. [1] [12]

L-Carnitine, acetyl-l-carnitine, and propionyl-l-carnitine are available in dietary supplement pills or powders, with a daily amount of 0.5 to 1 g considered to be safe. [1] [3] It is also a drug approved by the Food and Drug Administration to treat primary and certain secondary carnitine-deficiency syndromes secondary to inherited diseases. [1] [3]

Drug interactions and adverse effects

Carnitine interacts with pivalate-conjugated antibiotics such as pivampicillin. Chronic administration of these antibiotics increases the excretion of pivaloyl-carnitine, which can lead to carnitine depletion. [1] Treatment with the anticonvulsants valproic acid, phenobarbital, phenytoin, or carbamazepine significantly reduces blood levels of carnitine. [4]

When taken in the amount of roughly 3 grams (0.11 oz) per day, carnitine may cause nausea, vomiting, abdominal cramps, diarrhea, and body odor smelling like fish. [1] [4] Other possible adverse effects include skin rash, muscle weakness, or seizures in people with epilepsy. [4]

History

Levocarnitine was approved by the U.S. Food and Drug Administration as a new molecular entity under the brand name Carnitor on December 27, 1985. [4] [5]

See also

Related Research Articles

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

Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain isobutyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, and beans and other legumes. It is encoded by the codons UUA, UUG, CUU, CUC, CUA, and CUG. Leucine is named after the Greek word for "white": λευκός (leukós, "white"), after its common appearance as a white powder, a property it shares with many other amino acids.

<span class="mw-page-title-main">Ketogenesis</span> Chemical synthesis of ketone bodies

Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others.

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.

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. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. 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">Acetyl-CoA carboxylase</span> Enzyme that regulates the metabolism of fatty acids

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the cytoplasm of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. The human genome contains the genes for two different ACCs—ACACA and ACACB.

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

Malonyl-CoA is a coenzyme A derivative of malonic acid.

<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">Malonyl-CoA decarboxylase deficiency</span> Medical condition

Malonic aciduria or malonyl-CoA decarboxylase deficiency (MCD) is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-CoA decarboxylase. This enzyme breaks down Malonyl-CoA into acetyl-CoA and carbon dioxide.

<span class="mw-page-title-main">Acetylcarnitine</span> Form of L-carnitine

Acetyl-L-carnitine, ALCAR or ALC, is an acetylated form of L-carnitine. It is naturally produced by the human body, and it is available as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.

β-Hydroxybutyric acid Chemical compound

β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxybutyric acid is a chiral compound with two enantiomers: D-β-hydroxybutyric acid and L-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, D-β-hydroxybutyric acid is one of two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA2), a Gi/o-coupled G protein-coupled receptor (GPCR).

<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.

<span class="mw-page-title-main">Carnitine O-palmitoyltransferase</span>

Carnitine O-palmitoyltransferase is a mitochondrial transferase enzyme involved in the metabolism of palmitoylcarnitine into palmitoyl-CoA. A related transferase is carnitine acyltransferase.

<span class="mw-page-title-main">Acyl-CoA</span> Group of coenzymes that metabolize fatty acids

Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way, fats are converted to ATP, the universal biochemical energy carrier.

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:

Palmitoyl-CoA is an acyl-CoA thioester. It is an "activated" form of palmitic acid and can be transported into the mitochondrial matrix by the carnitine shuttle system, and once inside can participate in beta-oxidation. Alternatively, palmitoyl-CoA is used as a substrate in the biosynthesis of sphingosine.

<span class="mw-page-title-main">Carnitine palmitoyltransferase I</span> Enzyme found in humans

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.

The Randle cycle, also known as the glucose fatty-acid cycle, is a metabolic process involving the competition of glucose and fatty acids for substrates. It is theorized to play a role in explaining type 2 diabetes and insulin resistance.

<span class="mw-page-title-main">Carnitine O-octanoyltransferase</span>

Carnitine O-octanoyltransferase is a member of the transferase family, more specifically a carnitine acyltransferase, a type of enzyme which catalyzes the transfer of acyl groups from acyl-CoAs to carnitine, generating CoA and an acyl-carnitine. The systematic name of this enzyme is octanoyl-CoA:L-carnitine O-octanoyltransferase. Other names in common use include medium-chain/long-chain carnitine acyltransferase, carnitine medium-chain acyltransferase, easily solubilized mitochondrial carnitine palmitoyltransferase, and overt mitochondrial carnitine palmitoyltransferase. Specifically, CROT catalyzes the chemical reaction:

<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.

References

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  8. ↑ Tars K, Rumnieks J, Zeltins A, Kazaks A, Kotelovica S, Leonciks A, et al. (August 2010). "Crystal structure of human gamma-butyrobetaine hydroxylase". Biochemical and Biophysical Research Communications. 398 (4): 634–9. doi:10.1016/j.bbrc.2010.06.121. PMID   20599753.
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  10. ↑ Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q (April 2010). "Role of carnitine in disease". Nutrition & Metabolism. 7: 30. doi: 10.1186/1743-7075-7-30 . PMC   2861661 . PMID   20398344.
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  14. ↑ Nutrients Editorial Office (April 2018). "Erratum: l-Carnitine Supplementation in Recovery after Exercise; Nutrients 2018, 10, 349". Nutrients. 10 (5): 541. doi: 10.3390/nu10050541 . PMC   5986421 . PMID   29701693.
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