Niacin, essential to many types of life, is an example of a heterocyclic amine.

Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic (e.g., pyridine), though compounds exist in which this is not the case (e.g., the drug Zileuton). The biological functions of heterocyclic amines vary, including vitamins and carcinogens. Carcinogenic heterocyclic amines are created by high temperature cooking of meat and smoking of plant matter like tobacco. Some well known heterocyclic amines are niacin (vitamin B3), nicotine (psychoactive alkaloid and recreational drug), and the nucleobases that encode genetic information in DNA.

Five-membered heterocyclic amines

The compound pyrrolidine 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 naturally occurring organic compounds with nitrogen in them. 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.

Six-membered heterocyclic amines

The structure of pyridine 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 acids.

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 deficiency 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.

Heterocyclic amines and cancer

High-temperature cooking (particularly charring) of meat forms some cancer-causing heterocyclic amines.

Some heterocyclic amines (HCAs) found in cooked and especially burned meat are known carcinogens. Research has shown that heterocyclic amine formation in meat occurs at high cooking temperatures.[1] Heterocyclic amines are the carcinogenic chemicals formed from the cooking of muscle meats such as beef, lamb, pork, fish and poultry.[1][2] HCAs form when amino acids and creatine (a chemical found in muscles) react at high cooking temperatures.[1]

Several studies found that gastric[3], colorectal[4][5], pancreatic[6][7], prostate[8][9], and breast cancer[10] are associated with high intakes of well-done, fried, grilled, or barbecued meats. In particular, a 1997 study by the United States National Cancer Institute's Division of Cancer Epidemiology and Genetics found that people who eat well-done beef were more than three times as likely to suffer stomach cancer as those who ate rare or medium-rare beef.[3] Other sources of protein (milk, eggs, tofu, and organ meats such as liver) have very little or no HCA content naturally or when cooked.

Heterocyclic amines and neurological disorders

Harmane, a β-carboline alkaloid found in meats is "highly tremorogenic" (tremor inducing).[11][12] While harmane has been found in roughly 50% higher concentrations in patients with essential tremor than in controls,[13] 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.[12] 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.[14][15]

Heterocyclic amines and cooking

Research has shown that olive oil, lemon juice, and garlic marinade cut HCA levels in chicken by as much as 90%.[citation needed] 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.[16]

See also


  1. ^ a b c "National Cancer Institute – Heterocyclic Amines in Cooked Meats". September 15, 2004. Archived from the original on December 21, 2010. Retrieved May 1, 2010.
  2. ^ "Does eating processed and red meat cause cancer?". Retrieved 14 December 2022.
  3. ^ a b Ward MH, Sinha R, Heineman EF, Rothman N, Markin R, Weisenburger DD, Correa P, Zahm SH (March 1997). "Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference". Int J Cancer. 71 (1): 14–9. doi:10.1002/(sici)1097-0215(19970328)71:1<14::aid-ijc4>;2-6. PMID 9096659.
  4. ^ Cross AJ, Ferrucci LM, Risch A, Graubard BI, Ward MH, Park Y, Hollenbeck AR, Schatzkin A, Sinha R (March 2010). "A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association". Cancer Res. 70 (6): 2406–14. doi:10.1158/0008-5472.CAN-09-3929. PMC 2840051. PMID 20215514.
  5. ^ Chiavarini M, Bertarelli G, Minelli L, Fabiani R (May 2017). "Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis". Nutrients. 9 (5): 514. doi:10.3390/nu9050514. PMC 5452244. PMID 28524104.
  6. ^ Anderson KE, Sinha R, Kulldorff M, Gross M, Lang NP, Barber C, Harnack L, DiMagno E, Bliss R, Kadlubar FF (September 2002). "Meat intake and cooking techniques: associations with pancreatic cancer". Mutat Res. 506–507: 225–31. doi:10.1016/s0027-5107(02)00169-0. PMID 12351162.
  7. ^ Stolzenberg-Solomon RZ, Cross AJ, Silverman DT, Schairer C, Thompson FE, Kipnis V, Subar AF, Hollenbeck A, Schatzkin A, Sinha R (December 2007). "Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort". Cancer Epidemiol Biomarkers Prev. 16 (12): 2664–75. doi:10.1158/1055-9965.EPI-07-0378. PMID 18086772.
  8. ^ Cross AJ, Peters U, Kirsh VA, Andriole GL, Reding D, Hayes RB, Sinha R (December 2005). "A prospective study of meat and meat mutagens and prostate cancer risk". Cancer Res. 65 (24): 11779–84. doi:10.1158/0008-5472.CAN-05-2191. PMID 16357191.
  9. ^ Sinha R, Park Y, Graubard BI, Leitzmann MF, Hollenbeck A, Schatzkin A, Cross AJ (November 2009). "Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States". Am J Epidemiol. 170 (9): 1165–77. doi:10.1093/aje/kwp280. PMC 2781742. PMID 19808637.
  10. ^ Parada H, Steck SE, Bradshaw PT, Engel LS, Conway K, Teitelbaum SL, Neugut AI, Santella RM, Gammon MD (June 2017). "Grilled, Barbecued, and Smoked Meat Intake and Survival Following Breast Cancer". J Natl Cancer Inst. 109 (6): djw299. doi:10.1093/jnci/djw299. PMC 5214623. PMID 28052933.
  11. ^ Guan Y, Louis ED, Zheng W (December 2001). "Toxicokinetics of tremorogenic natural products, harmane and harmine, in male Sprague-Dawley rats". Journal of Toxicology and Environmental Health, Part A. 64 (8): 645–60. Bibcode:2001JTEHA..64..645G. doi:10.1080/152873901753246241. PMC 4992346. PMID 11766171.
  12. ^ a b Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P (August 2005). "Blood harmane concentrations and dietary protein consumption in essential tremor". Neurology. 65 (3): 391–6. doi:10.1212/01.wnl.0000172352.88359.2d. PMC 4993192. PMID 16087903.
  13. ^ Louis ED, Jiang W, Pellegrino KM, et al. (March 2008). "Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor". Neurotoxicology. 29 (2): 294–300. doi:10.1016/j.neuro.2007.12.001. PMC 2291546. PMID 18242711.
  14. ^ Chemicals in Meat Cooked at High Temperatures and Cancer Risk: NCI (accessed 13 February 2011).
  15. ^ Louis ED, Zheng W, Jiang W, Bogen KT, Keating GA (June 2007). "Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness". Journal of Toxicology and Environmental Health, Part A. 70 (12): 1014–9. Bibcode:2007JTEHA..70.1014L. doi:10.1080/15287390601172015. PMC 4993204. PMID 17497412.
  16. ^ Melo A, Viegas O, Petisca C, Pinho O, Ferreira IM (November 2008). "Effect of beer/red wine marinades on the formation of heterocyclic aromatic amines in pan-fried beef". Journal of Agricultural and Food Chemistry. 56 (22): 10625–32. doi:10.1021/jf801837s. PMID 18950185.