Biomarker: free carnitine

Histology type: endometrial carcinoma

Stage: risk

Country: ten European countries

Region: EPIC study

Study type: Observational Study

Followed up time :

Cohort statistics: Average

Description: These findings suggest that variation in levels of free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

Sample type : serum

Sample method: liquid chromatography-mass spectrometry

Subgroup 1 age: 63.0±7.9

Expression figure legend: Odds ratios (ORs) and P-values for the associations between metabolites and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models&Odds ratios (ORs) and P-values for the associations between metabolite ratios and risk of endometrial cancer in (A) unadjusted models (B) BMI-adjusted models.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336647/figure/f0005/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336647/figure/f0010/

Status: Detected and Quantified

HMDB ID: HMDB0000062

Secondary accession numbers: HMDB0001467 HMDB00062 HMDB01467

Common name: L-Carnitine

Description: Carnitine is a non-essential amino acid and a quaternary ammonium compound. Carnitine is also classified as an alcohol (specifically, a trimethylated carboxy-alcohol). Carnitine exists as one of two stereoisomers (the two enantiomers D-carnitine and L-carnitine. 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. Carnitine is involved in the metabolism in most mammals, plants, and some bacteria. Carnitine plays a key role in lipid metabolism and beta-oxidation. It is used to transport long-chain fatty acids into the mitochondria to be oxidized for energy production. This is done by forming a long chain acetylcarnitine esters which are then transported by carnitine palmitoyltransferase I and carnitine palmitoyltransferase II. Carnitine also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in skeletal and cardiac muscle as well as other tissues that metabolize fatty acids as an energy source. A normal 70 kilogram person typically produces 11-34 mg of carnitine per day. Adults eating mixed diets of red meat and other animal products ingest 60-180 mg of carnitine per day, while vegans consume about 10-12 mg per day. Most 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 in a person weighing 70 kilograms, with nearly all of it contained within skeletal muscle cells. Carnitine is so important in providing energy to muscles (including the heart) that some researchers are now recommending carnitine supplements in the diet, particularly for people who do not consume much red meat (the main food source for carnitine). Carnitine has been described as a vitamin, an amino acid, or a metabimin (i.e. an essential metabolite). Like the B vitamins, carnitine contains nitrogen and is very soluble in water. However, most animals, including humans, make their own carnitine; thus, carnitine cannot be considered to be a vitamin. In certain circumstances, such as methionine deficiency, lysine deficiency, vitamin C deficiency or kidney dialysis, carnitine shortages can develop. Under these conditions, carnitine must be absorbed from food, and for this reason, it is sometimes referred to as a "metabimin" or a conditionally essential metabolite. In humans, about 25% of carnitine is synthesized in the liver, kidney, and brain from lysine and methionine. Most of the carnitine in the body comes from dietary sources such as red meat and dairy products. Inborn errors of carnitine metabolism such as Reye’s syndrome can lead to brain deterioration gradually worsening muscle weakness, Duchenne-like muscular dystrophy, and extreme muscle weakness with fat accumulation in muscles. Carnitine is an essential nutrient for pre-term babies and individuals who are unable to eat a normal diet (e.g. non-ketotic hypoglycemics, kidney dialysis patients) (PMID: 115309 ). In conditions such as kwashiorkor, cirrhosis, and heart muscle disease (cardiomyopathy) as well as in inborn errors of metabolism such as type IV hyperlipidemia and propionic aciduria, carnitine is essential to life and carnitine supplements are critically important. Carnitine therapy may also be useful in a wide variety of clinical conditions. Carnitine supplementation has improved some patients who have angina secondary to coronary artery disease. Carnitine supplements may also be useful in many forms of metabolic liver diseases and heart muscle disease. Hearts undergoing severe arrhythmia quickly deplete their stores of carnitine. Athletes, particularly in Europe, have used carnitine supplements for improved endurance. Carnitine may improve muscle building by improving fat utilization and may even be useful in treating obesity. Carnitine may be of value in treating pregnant women, hypothyroid individuals, and male infertility due to the low motility of sperm. Carnitine deficiency is noted in abnormal liver function, renal dialysis patients, and severe to moderate muscular weakness with associated anorexia. Carnitine is a biomarker for the consumption of meat. In fact, carnitine was first extracted from meat extracts in 1905, leading to its name from Latin, "caro/carnis" or flesh.

Chemical formula: C7H15NO3

Chemical taxonomy description: Belongs to the class of organic compounds known as carnitines. These are organic compounds containing the quaternary ammonium compound carnitine.

Chemical taxonomy kingdom: Organic nitrogen compounds

Chemical taxonomy super class: Organonitrogen compounds

Chemical taxonomy class: Quaternary ammonium salts 

Chemical taxonomy sub class: Quaternary ammonium salts

Direct parent: Carnitines

Alternative parents: Short-chain hydroxy acids and derivatives Beta hydroxy acids and derivatives Fatty acids and conjugates Tetraalkylammonium salts Secondary alcohols Carboxylic acid salts 1,2-aminoalcohols Monocarboxylic acids and derivatives Carboxylic acids Organopnictogen compounds Organic zwitterions Organic salts Organic oxides Hydrocarbon derivatives Carbonyl compounds

Substituents: Carnitine Beta-hydroxy acid Short-chain hydroxy acid Fatty acid Hydroxy acid Tetraalkylammonium salt 1,2-aminoalcohol Carboxylic acid salt Secondary alcohol Carboxylic acid derivative Carboxylic acid Monocarboxylic acid or derivatives Organic oxygen compound Organooxygen compound Organic zwitterion Organic salt Hydrocarbon derivative Organic oxide Carbonyl group Organopnictogen compound Amine Alcohol Aliphatic acyclic compound

Molecular framework: Aliphatic acyclic compounds

Physiological effect: Adverse health effect Genetic disorder Inborn errors of metabolism Adrenoleukodystrophy Carnitine-acylcarnitine translocase deficiency (PMID: 1598097 , PMID: 7472823 ) Ethylmalonic encephalopathy (PMID: 10731506 , PMID: 27012787 , PMID: 3571488 , +12 More ) Mitochondrial trifunctional protein deficiency - Concentration is decreased compared to control group (PMID: 22492562 , PMID: 12215968 , PMID: 172850 , +14 More ) Nontypified gene mutations Organic acidemia L-2-hydroxyglutaric aciduria (PMID: 8134166 , PMID: 8412012 , PMID: 8134166 , +24 More ) Propionic acidemia (PMID: 24023812 , PMID: 6321058 , PMID: 20971021 , +65 More ) Digestive system disorder Gastrointestinal disorder Lower GI Disorder Colorectal cancer (PMID: 25037050 , PMID: 24023812 , PMID: 6321058 , +145 More ) Upper GI Disorder Eosinophilic esophagitis (PMID: 17334708 , PMID: 32966057 , PMID: 22623390 , +128 More ) Metabolic disorder Obesity (PMID: 4434100 , PMID: 1481808 , PMID: 2044610 , +66 More )

Disposition: Biological location Cellular substructure:Cytoplasm Organelle:Endoplasmic reticulum,Peroxisome Extracellular Non-excretory biofluid: Blood,Breast milk,Saliva,Semen Excreta:Feces,Urine,Tissue Connective tissue: Adipose tissue,Muscle tissue,Skeletal muscle Organ: Bladder,Brain,Heart,Intestine,Kidney,Liver,Lung,Placenta,Prostate,Cell Hematocyte:Erythrocyte,Platelet,Neuron

Associated disorders diseases: 114500 (Colorectal cancer) 236792 (L-2-Hydroxyglutaric aciduria) 605911 (3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency) 231530 (3-Hydroxyacyl-CoA dehydrogenase deficiency) 246450 (3-Hydroxy-3-methylglutaryl-CoA lyase deficiency) 616034 (2,4-dienoyl-CoA reductase deficiency) 212160 (Myopathic carnitine deficiency) 255120 (Carnitine palmitoyltransferase I deficiency) 212140 (Carnitine transporter defect; primary systemic carnitine deficiency) 609015 (Mitochondrial trifunctional protein deficiency) 603376 (Long-chain Fatty Acids, Defect in Transport of) 309000 (Oculocerebrorenal syndrome) 170650 (Periodontal disease) 260350 (Pancreatic cancer) 125853 (Diabetes mellitus type 2) 211980 (Lung Cancer) 610247 (Eosinophilic esophagitis) 606054 (Propionic acidemia) 601665 (Obesity)

KEGG compound ID: C00318

CPD link: https://www.genome.jp/dbget-bin/www_bget?cpd:C00318

Process: Beta oxidation of very long chain fatty acids Carnitine synthesis Mitochondrial beta-oxidation of long chain saturated fatty acids Mitochondrial beta-oxidation of short chain saturated fatty acids Oxidation of branched chain fatty acids Biochemical process Fatty acid metabolism System process Pregnancy (PMID: 21359215 , PMID: 23313728 , PMID: 22494326 , +145 More )

HMDB link: https://hmdb.ca/metabolites/HMDB0000062