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CARNITINE
DL-Carnitine=Carnitine=406-76-8
CAS: 406-76-8
European Community (EC) Number: 206-976-6
Formula: C7H15NO3
Molar mass: 161.199 g/mol
IUPAC Name: 3-hydroxy-4-(trimethylazaniumyl)butanoate
Carnitine is an amino-acid betaine that is butanoate substituted with a hydroxy group at position C-3 and a trimethylammonium group at C-4.
Carnitine has a role as a human metabolite and a mouse metabolite.
Carnitine derives from a butyrate.
Carnitine is a conjugate base of a carnitinium.
L-carnitine is a chemical that is made in the human brain, liver, and kidneys.
L-carnitine helps the body turn fat into energy.
L-carnitine is important for heart and brain function, muscle movement, and many other body processes.
The body can convert L-carnitine to other chemicals called acetyl-L-carnitine and propionyl-L-carnitine.
But it's not clear whether the benefits of these other carnitines are the same.
L-carnitine is used to increase L-carnitine levels in people whose natural level of L-carnitine is too low.
Some people also use L-carnitine for conditions of the heart and blood vessels, serious kidney disease, and many other conditions.
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 into mitochondria to be oxidized for 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.
Healthy individuals, including strict vegetarians, synthesize enough L-carnitine in vivo to not require supplementation.
Carnitine exists as one of two stereoisomers (the two enantiomers d-carnitine (S-(+)-) and l-carnitine (R-(-)-)).
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.
At room temperature, pure carnitine is a white powder, and a water-soluble zwitterion with low toxicity.
Derived from amino acids, carnitine was first extracted from meat extracts in 1905, leading to its name from Latin, "caro/carnis" or flesh.
Some individuals with genetic or medical disorders (such as preterm infants) cannot make enough carnitine, requiring dietary supplementation.
Many eukaryotes have the ability to synthesize carnitine, including humans.
Humans synthesize carnitine from the substrate TML (6-N-trimethyllysine), which is in turn derived from the methylation of the amino acid lysine.
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 (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.
Gamma-butyrobetaine is then hydroxylated by gamma butyrobetaine hydroxylase (a zinc binding enzyme) into l-carnitine, requiring iron in the form of Fe2+.
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.
Carnitine also plays a role in stabilizing Acetyl-CoA and coenzyme A levels through the ability to receive or give an acetyl group.
The tissue distribution of carnitine-biosynthetic enzymes in humans indicates TMLD to be active in the liver, heart, muscle, brain and highest in kidney.
HTMLA activity is found primarily in the liver.
The rate of TMABA oxidation is greatest in the liver, with considerable activity also in the kidney.
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.
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.
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 molecule 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.
In the second reaction, acyl-CoA is transiently attached to the hydroxyl group of carnitine to form fatty acyl–carnitine.
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).
The fatty acyl–carnitine ester formed then diffuses across the intermembrane space and enters the matrix by facilitated diffusion through carnitine-acylcarnitine translocase (CACT) located on inner mitochondrial membrane.
This antiporter return one molecule of carnitine from the matrix to the intermembrane space for every one molecule of fatty acyl–carnitine that moves into the matrix.
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.
L-Carnitine inner salt has been used as a component of an assay medium for Seahorse XF mitochondrial stress assay.
Carnitine biosynthesized from lysine.
Carnitine facilitates fatty acid transport into the mitochondrial compartment.
In skeletal and cardiac muscle tissue carnitine acts as a metabolic cofactor.
Carnitine might be associated with the energy production from branched chain amino acids.
Carnitine is a quaternary amine that occurs naturally in most mammalian tissue.
Carnitine is present in relatively high concentrations in skeletal muscle and heart where it is involved in regulating energy metabolism.
Carnitine shifts glucose metabolism from glycolysis to glycogen storage and enhances the transport of long chain fatty acids into the mitochondria where they are oxidized for energy production.
Carnitine, or transliteration carnitine, is an amino acid that belongs to the quaternary ammonium cation complex and can be biosynthetically synthesized from lysine and methionine amino acids.
There are two stereoisomeric isomers of carnitine: including biologically active L-carnitine, and its non-biologically active enantiomeric D-carnitine.
Compounds that are chemically synthesized and both L and D carnitine are present are generally labeled as "DL-carnitine."
In China, L-carnitine has a more common trade name: L-carnitine or L-carnitine.
L-Carnitine was originally discovered as a growth factor for Tenebrio molitor, which was once named Vitamin Bt.
In living cells, when fat metabolism produces energy, carnitine is required to transport fatty acids from the cytosol to the mitochondria to prevent fatty acids from accumulating in the cells.
Around the world, carnitine is often packaged as a nutritional supplement and is claimed to help burn fat and help lose weight.
L-Carnitine (β-hydroxy-γ-N-trimethylaminobutyric acid) is a derivative of the amino acid, lysine.
L-Carnitine was first isolated from meat (carnus in Latin) in 1905.
Only the L-isomer of carnitine is biologically active.
L-Carnitine appeared to act as a vitamin in the mealworm (Tenebrio molitor) and was therefore termed vitamin BT.
Vitamin BT, however, is a misnomer because humans and other higher organisms can synthesize L-carnitine.
Under certain conditions, the demand for L-carnitine may exceed an individual's capacity to synthesize it, making it a conditionally essential nutrient.
In healthy people, carnitine homeostasis is maintained through endogenous biosynthesis of L-carnitine, absorption of carnitine from dietary sources, and reabsorption of carnitine by the kidneys.
Humans can synthesize L-carnitine from the amino acids lysine and methionine in a multi-step process occurring across several cell compartments (cytosol, lysosomes, and mitochondria).
Across different organs, protein-bound lysine is methylated to form ε-N-trimethyllysine in a reaction catalyzed by specific lysine methyltransferases that use S-adenosyl-methionine (derived from methionine) as a methyl donor.
ε-N-Trimethyllysine is released for carnitine synthesis by protein hydrolysis.
Four enzymes are involved in endogenous L-carnitine biosynthesis.
They are all ubiquitous except γ-butyrobetaine hydroxylase is absent from cardiac and skeletal muscle.
This enzyme is, however, highly expressed in human liver, testes, and kidney.
L-carnitine is primarily synthesized in the liver and transported via the bloodstream to cardiac and skeletal muscle, which rely on L-carnitine for fatty acid oxidation yet cannot synthesize it.
The rate of L-carnitine biosynthesis in humans was studied in strict vegetarians (i.e., in people who consume very little dietary carnitine) and estimated to be 1.2 µmol/kg of body weight/day.
The rate of L-carnitine synthesis depends on the extent to which peptide-linked lysines are methylated and the rate of protein turnover.
There is some indirect evidence to suggest that excess lysine in the diet may increase endogenous L-carnitine synthesis; however, changes in dietary carnitine intake level or in renal reabsorption do not appear to affect the rate of endogenous L-carnitine synthesis.
The bioavailability of L-carnitine from food can vary depending on dietary composition.
For instance, one study reported that bioavailability of L-carnitine in individuals adapted to low-carnitine diets (i.e., vegetarians) was higher (66%-86%) than in those adapted to high-carnitine diets (i.e., regular red meat eaters; 54%-72%).
The remainder is degraded by colonic bacteria.
L-Carnitine and short-chain acylcarnitine derivatives are excreted by the kidneys.
Renal reabsorption of free L-carnitine is normally very efficient; in fact, an estimated 95% is thought to be reabsorbed by the kidneys.
Therefore, carnitine excretion by the kidney is usually very low.
However, several conditions can decrease the efficiency of carnitine reabsorption and, correspondingly, increase carnitine excretion.
Such conditions include high-fat, low-carbohydrate diets; high-protein diets; pregnancy; and certain disease states.
In addition, when circulating L-carnitine concentration increases, as in the case of oral supplementation, renal reabsorption of L-carnitine may become saturated, resulting in increased urinary excretion of L-carnitine.
Dietary or supplemental L-carnitine that is not absorbed by enterocytes is degraded by colonic bacteria to form two principal products, trimethylamine and γ-butyrobetaine.
γ-Butyrobetaine is eliminated in the feces; trimethylamine is efficiently absorbed and metabolized to trimethylamine-N-oxide, which is excreted in the urine.
L-Carnitine is synthesized primarily in the liver but also in the kidneys and then transported to other tissues.
L-Carnitine is most concentrated in tissues that use fatty acids as their primary fuel, such as skeletal and cardiac muscle.
In this regard, L-carnitine plays an important role in energy production by conjugating to fatty acids for transport from the cytosol into the mitochondria.
L-Carnitine is required for mitochondrial β-oxidation of long-chain fatty acids for energy production.
Long-chain fatty acids must be esterified to L-carnitine (acylcarnitine) in order to enter the mitochondrial matrix where β-oxidation occurs.
On the outer mitochondrial membrane, CPTI (carnitine-palmitoyl transferase I) catalyzes the transfer of medium/long-chain fatty acids esterified to coenzyme A (CoA) to L-carnitine.
This reaction is a rate-controlling step for the β-oxidation of fatty acid.
A transport protein called CACT (carnitine-acylcarnitine translocase) facilitates the transport of acylcarnitine across the inner mitochondrial membrane.
On the inner mitochondrial membrane, CPTII (carnitine-palmitoyl transferase II) catalyzes the transfer of fatty acids from L-carnitine to free CoA.
Fatty acyl-CoA is then metabolized through β-oxidation in the mitochondrial matrix, ultimately yielding propionyl-CoA and acetyl-CoA.
Carnitine is eventually recycled back to the cytosol.
Endogenous biosynthesis of L-carnitine is catalyzed by the concerted action of four different enzymes.
This process requires two essential amino acids (lysine and methionine), iron (Fe2+), vitamin B6 in the form of pyridoxal 5’-phosphate, niacin in the form of nicotinamide adenine dinucleotide (NAD), and may also require vitamin C (ascorbate).
One of the earliest symptoms of vitamin C deficiency is fatigue, thought to be related to decreased synthesis of L-carnitine.
L-carnitine, also known as levocarnitine, is a naturally occurring amino acid structure that the body produces.
People can also get L-Carnitine from their diet or take it in the form of an oral supplement.
L-carnitine plays a critical role in energy production, as it converts fat into energy.
Most people will get enough L-carnitine from their diet or their body’s production of this compound.
Those with low L-carnitine levels may benefit from taking an oral supplement, though.
As well as supporting energy production, L-carnitine may help some other functions in the body, such as maintaining general brain function and reducing the risk of certain disorders.
L-carnitine is a type of carnitine, which is a derivative of amino acids.
Amino acids combine to make proteins, which carry out many essential tasks in the body.
Carnitine helps the body break down fatty acids and turn them into energy to power the cells.
L-carnitine is a conditionally essential nutrient, meaning that the body can generally make enough of it, but, in some cases, a person may have to get the compound from food or oral supplements if they cannot make enough.
In the body, the liver and kidneys create L-carnitine from the amino acids lysine and methionine.
The kidneys can also store L-carnitine for later use and eliminate the excess through the urine stream.
Carnitine is a broad term that describes a few different compounds.
L-carnitine is a more common form of carnitine, present in the body and many supplements.
Other forms of carnitine include:
Acetyl L-carnitine: This form, sometimes known as ALCAR, also plays a role in metabolism.
Acetyl L-carnitine possesses neuroprotective properties that may help protect the nervous system.
D-carnitine: This type is the optical isomer (mirror image) of L-carnitine.
D-carnitine is toxic to the body, as it may inhibit the absorption of other forms of carnitine.
L-carnitine L-tartrate: Athletes may use this type in the form of sports supplements.
Research suggests that L-carnitine L-tartrate may be useful in minimizing muscle soreness and aiding recovery.
Propionyl-L-carnitine: This form displays pain relieving and antirheumatic properties, and it may benefit heart health.
L-carnitine, and carnitine in general, is a key component in creating energy for the cells.
L-carnitine's main function, helping break down fatty acids for use as energy, keeps the body’s cells powered and working efficiently.
L-carnitine also has a secondary function of helping remove some waste products from the cells to prevent them from accumulating and causing problems.
Supplementation may help improve L-carnitine levels in a failing heart, which could boost heart health and circulation in the short term following a heart attack.
Supplementation may also help with symptoms of heart failure, such as chest pain and arrhythmia.
At times, cancer treatments, such as chemotherapy, may cause a person to become deficient in L-carnitine.
In these cases, L-carnitine supplements may help reduce symptoms such as fatigue and weakness.
As the kidneys and liver help create and use L-carnitine, disease in these organs or organ failure may lead to L-carnitine deficiency.
Doctors may recommend L-carnitine supplementation in these cases to support the function of the kidneys and liver and prevent deficiency.
The carnitine-mediated entry process is a rate-limiting factor for fatty acid oxidation and is an important point of regulation.
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.
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 disinhibits carnitine acyltransferase 1, allowing fatty acid import to the mitochondria, ultimately replenishing the supply of ATP.
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.
Infants, especially premature infants, have low stores of carnitine, necessitating use of carnitine-fortified infant formulas as a replacement for breast milk, if necessary.
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.
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 use of antibiotics, malnutrition, and poor absorption following digestion.
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.
Red meats tend to have higher levels of l-carnitine.
Adults eating diverse diets that contain animal products attain about 23-135 mg of carnitine per day.
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.
Even carnitine-poor diets have little effect on total carnitine content, as the kidneys conserve carnitine.
In general, omnivorous humans each day consume between 2 and 12 µmol kg−1 of body weight, accounting for 75% of carnitine in the body.
Humans endogenously produce 1.2 µmol kg−1 of body weight of carnitine on a daily basis, accounting for 25% of the carnitine in the body.
Strict vegetarians obtain little carnitine from dietary sources (0.1 µmol kg−1 of body weight daily), as it is mainly found in animal-derived foods.
Effective for
L-carnitine deficiency.
Taking L-carnitine by mouth or by IV is effective for treating L-carnitine deficiency caused by certain genetic diseases or other disorders.
It's approved by the FDA for this use.
IV products can only be given by a healthcare provider.
Possibly Effective for
Chest pain (angina).
Taking L-carnitine by mouth or by IV seems to improve exercise tolerance in people with chest pain.
Taking L-carnitine along with standard treatment also seems to reduce chest pain and improve exercise ability in people with cardiac syndrome X.
People with this condition have chest pain but not blocked arteries. IV products can only be given by a healthcare provider.
Heart failure and fluid build up in the body (congestive heart failure or CHF). Taking L-carnitine by mouth or by IV seems to improve symptoms and increase exercise ability in people with heart failure. IV products can only be given by a healthcare provider.
High levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia). Taking L-carnitine by mouth or by IV can improve cholesterol and triglyceride levels by a small amount. IV products can only be given by a healthcare provider.
Kidney failure. The FDA has approved giving L-carnitine by IV, but not by mouth, for kidney failure. This can only be given by a healthcare provider.
Conditions in a male that prevent a female partner from getting pregnant (male infertility). Taking L-carnitine by mouth, alone or together with acetyl-L-carnitine, increases sperm count and sperm movement in males with fertility problems. Some research shows that this increases the chance of pregnancy.
Swelling (inflammation) of the heart (myocarditis). Some children who have had diphtheria can develop myocarditis. Taking DL-carnitine by mouth seems to reduce the risk of myocarditis and death in these children.
A hormonal disorder that causes enlarged ovaries with cysts (polycystic ovary syndrome or PCOS). Taking L-carnitine by mouth can increase ovulation and the chance of getting pregnant in people who don't respond to the medication clomiphene. Also, taking L-carnitine might help with weight loss and improving blood sugar levels.
Toxic side effects caused by the drug valproic acid. Toxicity caused by valproic acid seems to be linked with L-carnitine deficiency. Taking L-carnitine by mouth or by IV can prevent liver toxicity from valproic acid. IV products can only be given by a healthcare provider.
Functions and Applications
1. Infant food: L-carnitine can be added to milk powder to improve the nutrition.
2. Weight loss: L-carnitine can burn the redundant adipose in our body, then transmit to energy, which can help us lose weight.
3. Athletes food: L-carnitine is good for improve the explosive force and resist fatigue, which can enhance our sports ability.
4. Important nutritional supplement for human body: With the growth of our age, the content of L-carnitine in our body is decreasing, so we should supplement L-carnitine to maintain the health of our body.
5. L-Carnitine is proved to be safe and healthy food after security experiments in many countries.
SYNONYMS:
DL-Carnitine
Carnitine
406-76-8
Carnitine DL-form
Carnitina
3-hydroxy-4-(trimethylammonio)butanoate
3-hydroxy-4-(trimethylazaniumyl)butanoate
L(-)-Carnitine
461-06-3
Carnitine [INN]
D,L-carnitine
Levocarnitine;Vitamin B(T)
(+/-)-Carnitin
Carnicor
CHEBI:17126
MFCD00038747
(+-)-Carnitine
Excitine
Miotonal
Novaine
Vitacarn
Carnum
Miocor
Novain
EINECS 206-976-6
Prestwick_877
L-Carnitine Complex
L-Carnitine (Base)
L-Carnitine Base27
ACMC-209ld6
SCHEMBL21971
CHEMBL172513
DTXSID3022744
HY-B0399A
(1)-(3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide
BCP02286
BCP07697
5526AB
STL356005
AKOS006229283
AM82464
CS-4771
MCULE-6432281267
NSC 757390
AMMONIUM, (3-CARBOXY-2-HYDROXYPROPYL)TRIMETHYL-, HYDROXIDE, inner salt, DL-
SY076118
AB0011079
DB-052482
DB-052484
FT-0603460
FT-0625449
FT-0632349
11102-EP2269610A2
11102-EP2289510A1
11102-EP2316457A1
11102-EP2316458A1
11102-EP2316825A1
11102-EP2316826A1
11102-EP2316827A1
11102-EP2316828A1
Q243309
F0001-2377
(R)-(3-Carboxy-2-hydroxypropyl)trimethylammonium, inner salt
(R)-3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium, inner salt
1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, inner salt,(2R)-
1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, hydroxide, inner salt, (+-)- (9CI)
