Heterocyclic amines
Encyclopedia
Heterocyclic amines, also sometime referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, plus the compound has at least one amine
group. While some heterocycles are amines themselves, the amines indicated in the name are those attached to the heterocyclic ring. The biological function of heterocyclic amines can range from those of vitamin
s to carcinogen
s. Carcinogenic heterocyclic amines are created by high temperature cooking of meat, for example.
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 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, which are amines found in nature and produce physiological changes in animals.
Pyrrole
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
.
The rings of porphyrin
are components of hemoglobin
, myoglobin
, vitamin B12
, chlorophyll
and cytochromes. In the centers of heme
in hemoglobin, myoglobin and cytochromes, iron is an ion, in the first two iron ion is bound to oxygen.
is similar to that of benzene
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: niacin
and pyridoxine
.
Niacin, also called nicotinic acid, is found in most organisms. Via metabolism, it becomes nicotinamide adenine dinucleotide NAD, a coenzyme which is involved in oxidation and reduction in metabolic cells. A deficiency of niacin leads to a disease called pellagra
.
Pyridoxine or vitamin B6, it becomes a major compound in the metabolism of amino acid
s.
Pyrimidine
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
, which is also known as vitamin B1. Thiamine decifiency produces beriberi
.
Pyrimidine is a component of the nucleobases cytosine, uracil and thymine. The other two nucleobases, adenine
and guanine
, are also heterocyclic amines called purines; they are composed of a fused pyrimidine and imidazole
.
s. Research has shown that heterocyclic amine formation in meat
occurs at high cooking temperatures. For example, heterocyclic amines are the carcinogenic chemicals formed from the cooking of muscle meats such as beef
, pork
, fowl
, and fish
. HCAs form when amino acids and creatine
(a chemical found in muscles) react at high cooking temperatures. Researchers have identified 17 different HCAs resulting from the cooking of muscle meats that may pose human cancer risk. NCI's Division of Cancer Epidemiology and Genetics found a link between individuals with stomach cancer
and the consumption of cooked meat, and other studies for colorectal, pancreatic, and breast cancer
is associated with high intakes of well-done, fried, or barbecue
d meats. People who eat medium-well or well done beef were more than three times as likely to suffer stomach cancer as those who ate rare or medium-rare beef. Other sources of protein
(milk
, eggs
, tofu
, and organ meats such as liver
) have very little or no HCA content naturally or when cooked.
Harmane has been found in roughly 50% higher concentrations in patients with essential tremor
than in controls; essential tremor is a condition 20 times more prevalent than Parkinson's disease
. 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.
and processed meat is to eat less of it overall".
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
group. While some heterocycles are amines themselves, the amines indicated in the name are those attached to the heterocyclic ring. The biological function of heterocyclic amines can range from those of vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s to carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s. Carcinogenic heterocyclic amines are created by high temperature cooking of meat, for example.
Five-membered heterocyclic amines
The compound pyrrolidinePyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula C4H9N. It is a cyclic secondary amine with a five-membered heterocycle containing four carbon atoms and one nitrogen atom...
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 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, which are amines found in nature and produce physiological changes in animals.
Pyrrole
Pyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...
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
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
.
The rings of porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
are components of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
, vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
, chlorophyll
Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria. Its name is derived from the Greek words χλωρος, chloros and φύλλον, phyllon . Chlorophyll is an extremely important biomolecule, critical in photosynthesis, which allows plants to obtain energy from light...
and cytochromes. In the centers of heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
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 pyridinePyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
is similar to that of benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
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: niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
and pyridoxine
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
.
Niacin, also called nicotinic acid, is found in most organisms. Via metabolism, it becomes nicotinamide adenine dinucleotide NAD, a coenzyme which is involved in oxidation and reduction in metabolic cells. A deficiency of niacin leads to a disease called pellagra
Pellagra
Pellagra is a vitamin deficiency disease most commonly caused by a chronic lack of niacin in the diet. It can be caused by decreased intake of niacin or tryptophan, and possibly by excessive intake of leucine. It may also result from alterations in protein metabolism in disorders such as carcinoid...
.
Pyridoxine or vitamin B6, it becomes a major compound in the metabolism of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s.
Pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
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
Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...
, which is also known as vitamin B1. Thiamine decifiency produces beriberi
Beriberi
Beriberi is a nervous system ailment caused by a thiamine deficiency in the diet. Thiamine is involved in the breakdown of energy molecules such as glucose and is also found on the membranes of neurons...
.
Pyrimidine is a component of the nucleobases cytosine, uracil and thymine. The other two nucleobases, adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
and guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
, are also heterocyclic amines called purines; they are composed of a fused pyrimidine and imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
.
Heterocyclic amines and cancer
Some heterocyclic amines (HCAs) found in cooked and especially burned meat are known carcinogenCarcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s. Research has shown that heterocyclic amine formation in meat
Heterocyclic amine formation in meat
- Heterocyclic Amines, Meat, and Cancer :After scientists discovered the carcinogenic components in cigarette smoke, they questioned whether carcinogens could also be found in foods that were smoked or burned, such as meats In 1977, cancer-causing compounds, now known to be heterocyclic amine, were...
occurs at high cooking temperatures. For example, heterocyclic amines are the carcinogenic chemicals formed from the cooking of muscle meats such as beef
Beef
Beef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...
, pork
Pork
Pork is the culinary name for meat from the domestic pig , which is eaten in many countries. It is one of the most commonly consumed meats worldwide, with evidence of pig husbandry dating back to 5000 BC....
, fowl
Fowl
Fowl is a word for birds in general but usually refers to birds belonging to one of two biological orders, namely the gamefowl or landfowl and the waterfowl...
, and fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
. HCAs form when amino acids and creatine
Creatine
Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
(a chemical found in muscles) react at high cooking temperatures. Researchers have identified 17 different HCAs resulting from the cooking of muscle meats that may pose human cancer risk. NCI's Division of Cancer Epidemiology and Genetics found a link between individuals with stomach cancer
Stomach cancer
Gastric cancer, commonly referred to as stomach cancer, can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs, lymph nodes, and the liver...
and the consumption of cooked meat, and other studies for colorectal, pancreatic, and breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
is associated with high intakes of well-done, fried, or barbecue
Barbecue
Barbecue or barbeque , used chiefly in the United States, Canada, the United Kingdom, New Zealand and Australia is a method and apparatus for cooking meat, poultry and occasionally fish with the heat and hot smoke of a fire, smoking wood, or hot coals of...
d meats. People who eat medium-well or well done beef were more than three times as likely to suffer stomach cancer as those who ate rare or medium-rare beef. Other sources of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
(milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
, eggs
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...
, tofu
Tofu
is a food made by coagulating soy milk and then pressing the resulting curds into soft white blocks. It is part of East Asian and Southeast Asian cuisine such as Chinese, Japanese, Korean, Indonesian, Vietnamese, and others. There are many different varieties of tofu, including fresh tofu and tofu...
, and organ meats such as liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
) have very little or no HCA content naturally or when cooked.
Heterocyclic amines and neurological disorders
Harmane, a β-carboline alkaloid found in meats, has been shown to have strong neurotoxic characteristics, and in particular, is 'highly tremorogenic.' 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.Harmane has been found in roughly 50% higher concentrations in patients with essential tremor
Essential tremor
Essential tremor is a slowly progressive neurological disorder whose most recognizable feature is a tremor of the arms that is apparent during voluntary movements such as eating and writing...
than in controls; essential tremor is a condition 20 times more prevalent than Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. 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.
Heterocyclic amines and cooking
Research has shown that an olive oil, lemon juice and garlic marinade cut HCA levels in chicken by as much as 90%. 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. However, researchers say that "It may seem appetising to marinate steak in beer or wine, but this will have a minimal impact on the effect of the meat on your cancer risk and the best way to reduce your risk of cancer from eating redRed meat
Red meat in traditional culinary terminology is meat which is red when raw and not white when cooked. In the nutritional sciences, red meat includes all mammal meat. Red meat includes the meat of most adult mammals and some fowl ....
and processed meat is to eat less of it overall".