Introduction
Main research field of this group is the study of properties of main enzymes of drug metabolism, cytochromes P450. These enzymes metabolize, generally speaking, most of the xenobiotics (drugs, environmental pollutants etc.). Cytochromes P450 are hemoproteins known to bind molecular oxygen and nonpolar substrates. Molecular oxygen is in the majority of P450-catalyzed reactions activated and subsequently splitted to two atoms, one of them is then incorporated (by monooxygenation reaction) into substrate molecule forming mostly hydroxylated products and the second forms water molecule.
The reaction is conditioned by uptake of two electrons from the
respective coenzymes (NADPH+ or NADP+). Cytochromes P450 are responsible for
metabolism of more than three thirds of drugs with known metabolic pathways.
This is also why they are often responsible for bioavailability of a drug,
in other words, for effective concentration level in the target tissue.
Also, drug interactions at the level of drug metabolism are in most cases due to
competition, inhibition or induction of P450 enzymes. These enzymes are not only
metabolizing drugs, they also participate in biosynthetic pathways leading to
production of many important endogenous compounds as e.g. steroid hormones,
prostaglandins, thromboxanes. NO synthase, an enzyme of the last decade of the
20th century, is by its enzyme mechanism also a P450.
Studies on P450s begun with its discovery in1958; in former Czechoslovakia, a pioneer in drug metabolism studies was the late Prof. Antonín Jindra (Charles U., in Prague, then Comenius University in Bratislava).