Heterocyclic amines

Abstract

Heterocyclic amines (HAs), also known as heterocyclic aromatic amines (HAAs), include many carcinogenic compounds produced during cooking. Heterocyclic amines (HA) are potent mutagens and potential carcinogens. Cooking of flesh foods, including beef, pork, poultry, and fish, produces microgram amounts of HAs per serving from the pyrolytic rearrangement of creatine and amino acids. The site, mechanism, and effectiveness of HA uptake from the intestinal lumen has not been understood completely. More is known about several transporters that pump HAs back into the lumen, some of it from circulating blood. At equal concentrations, the basolateral to apical efflux is several-fold greater than the apical to basolateral influx. Metabolism of xenobiotics often involves two types of metabolic processes, mainly in the liver, and to a lesser extent, in the kidney and other organs. The first, activating reactions, are referred to as phase I reactions. Phase I reactions most often involve hydroxylation or oxidation of the compound; a variety of other reactions are also possible. The second type, the phase II reactions, include conjugating and other modifying reactions. These molecular modifications tend to make the original compound more polar and enhance their renal excretion. Phase I reactions often increase the reactivity of xenobiotics towards DNA and proteins. Phase II enzymes, on the other hand, tend to decrease the potential for harm by speeding up their elimination. The bulk of HAs is excreted with urine as glucuronide conjugates that are freely filtered.