Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

ring, which by definition has atoms of at least two different elements, as well as at least one

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

(nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic (e.g.,

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

), though compounds exist in which this is not the case (e.g., the drug

zileuton Zileuton (trade name Zyflo) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laborato ...

). The biological functions of heterocyclic amines vary, including

vitamin Vitamins are Organic compound, organic molecules (or a set of closely related molecules called vitamer, vitamers) that are essential to an organism in small quantities for proper metabolism, metabolic function. Nutrient#Essential nutrients, ...

s and

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

s. Carcinogenic heterocyclic amines are created by high temperature cooking of meat and smoking of plant matter like

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

. Some well known heterocyclic amines are

niacin Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

(vitamin B3), nicotine (psychoactive alkaloid and recreational drug), and the

nucleobase Nucleotide bases (also nucleobases, nitrogenous bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nuc ...

s that encode genetic information in DNA.

Five-membered heterocyclic amines

The compound

pyrrolidine Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...

is composed of molecules that contain a saturated ring of five atoms. This cyclic structure is composed of one atom of nitrogen and four carbon.

Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

is a molecule containing a pyrrolidine ring attached to a ring of pyridine (other heterocyclic amine). Nicotine belongs to a group of compounds known as

alkaloids Alkaloids are a broad class of naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large variety of organisms i ...

, which are naturally occurring organic compounds with nitrogen in them.

Pyrrole Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula . It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-methylpyrrol ...

is another compound made up of molecules with a five-membered heterocyclic ring. These molecules are unsaturated and contain a nitrogen atom in the ring. Four pyrrole rings are joined in a ring structure called a

porphyrin Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, w ...

. The rings of

are components of

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

myoglobin Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle, skeletal Muscle, muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compar ...

vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. One of eight B vitamins, it serves as a vital cofactor (biochemistry), cofactor in DNA synthesis and both fatty acid metabolism, fatty acid and amino a ...

chlorophyll Chlorophyll is any of several related green pigments found in cyanobacteria and in the chloroplasts of algae and plants. Its name is derived from the Greek words (, "pale green") and (, "leaf"). Chlorophyll allows plants to absorb energy ...

, and

cytochromes Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...

. In the centers of

heme Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...

in hemoglobin, myoglobin, and cytochromes, iron is an ion; in the first two, iron ion is bound to oxygen.

Six-membered heterocyclic amines

The structure of

is similar to that of

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

except that a nitrogen atom replaces one carbon atom. Pyridine is used as a flavoring agent. The pyridine ring is part of two B vitamins:

and

pyridoxine Pyridoxine (PN) is a form of vitamin B6 found commonly in food and used as a dietary supplement. As a supplement it is used to treat and prevent pyridoxine deficiency, sideroblastic anaemia, pyridoxine-dependent epilepsy, certain metaboli ...

. Niacin, also called nicotinic acid, is found in most organisms. Via metabolism, it becomes nicotinamide adenine dinucleotide NAD, a

coenzyme A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can ...

which is involved in oxidation and reduction in metabolic cells. A deficiency of niacin leads to a disease called

pellagra Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to friction and radiation are typically affected first. Over tim ...

. Pyridoxine or vitamin B6, it becomes a major compound in the metabolism of

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

Pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

is a heterocyclic amine that contains two nitrogen atoms in an unsaturated six-membered ring. An example of a molecule that contains pyrimidine is

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...

, which is also known as vitamin B1. Thiamine deficiency produces

beriberi Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). A severe and chronic form is known as beriberi. The name beriberi was possibly borrowed in the 18th century from the Sinhalese phrase (bæri bæri, “I canno ...

. Pyrimidine is a component of the

nucleobases Nucleotide bases (also nucleobases, nitrogenous bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nuc ...

cytosine, uracil, and thymine. The other two nucleobases,

adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...

and

guanine Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...

, are also heterocyclic amines called

purines Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which inc ...

; they are composed of a fused pyrimidine and

imidazole Imidazole (ImH) is an organic compound with the formula . It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. It can be classified as a heterocycle, specifically as a diazole. Many natural products, ...

Heterocyclic amines and cancer

Some HCAs found in cooked and especially burned meat are known

s. Research has shown that heterocyclic amine formation in meat occurs at high cooking temperatures. Heterocyclic amines are the carcinogenic chemicals formed from the cooking of muscle meats such as

beef Beef is the culinary name for meat from cattle (''Bos taurus''). Beef can be prepared in various ways; Cut of beef, cuts are often used for steak, which can be cooked to varying degrees of doneness, while trimmings are often Ground beef, grou ...

, lamb,

pork Pork is the culinary name for the meat of the pig (''Sus domesticus''). It is the most commonly consumed meat worldwide, with evidence of pig animal husbandry, husbandry dating back to 8000–9000 BCE. Pork is eaten both freshly cooke ...

, fish and poultry. HCAs form when

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

and

creatine Creatine ( or ) is an organic compound with the nominal formula . It exists in various tautomers in solutions (among which are neutral form and various zwitterionic forms). Creatine is found in vertebrates, where it facilitates recycling of ...

(a chemical found in muscles) react at high cooking temperatures.

Colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

is associated with high intakes of HCAs found in meat cooked at high temperature. Six hours of marinating in beer or red wine cut levels of two types of HCA in beef steak by up to 90% compared with unmarinated steak.

Heterocyclic amines and neurological disorders

Harmane, a β-carboline alkaloid found in meats is "highly tremorogenic" (tremor inducing). While harmane has been found in roughly 50% higher concentrations in patients with

essential tremor Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations ( oscillations or twitching movements) of certain muscle groups i ...

than in controls, there is no direct correlation between blood-levels and levels of daily meat consumption, suggesting a difference in metabolism of this chemical plays a greater role. These chemicals are formed during the cooking process of meat, particularly the longer they are cooked, and the more they are exposed to high temperatures during cooking.Chemicals in Meat Cooked at High Temperatures and Cancer Risk: NCI (accessed 13 February 2011).
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References

External links