Enzymes are protein catalysts facilitating the conversion of substrates into products. The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) classifies enzymes into families, using a four number code, on the basis of the reactions they catalyse. There are six main families:

EC 1.-.-.- Oxidoreductases;
EC 2.-.-.- Transferases;
EC 3.-.-.- Hydrolases;
EC 4.-.-.- Lyases;
EC 5.-.-.- Isomerases;
EC 6.-.-.- Ligases.

Although there are many more enzymes than receptors in biology, and many drugs that target prokaryotic enzymes are effective medicines, overall the number of enzyme drug targets is relatively small [1-2], which is not to say that they are of modest importance.

The majority of drugs which act on enzymes act as inhibitors; one exception is ingenol mebutate, which is a non-selective protein kinase C activator approved for the topical treatment of actinic keratoses. Kinetic assays allow discrimination of competitive, non-competitive, and un-competitive inhibitors. The majority of inhibitors are competitive (acting at the enzyme's ligand recognition site), non-competitive (acting at a distinct site; potentially interfering with co-factor or co-enzyme binding) or of mixed type. One rare example of an uncompetitive inhibitor is lithium ions, which are effective inhibitors at inositol monophosphatase only in the presence of high substrate concentrations. Some inhibitors are irreversible, including a group known as suicide substrates, which bind to the ligand recognition site and then couple covalently to the enzyme. It is beyond the scope of the Guide to give mechanistic information about the inhibitors described, although generally this information is available from the indicated literature.

Many enzymes require additional entities for functional activity. Some of these are used in the catalytic steps, while others promote a particular conformational change. Co-factors are tightly bound to the enzyme and include metal ions and heme groups. Co-enzymes are typically small molecules which accept or donate functional groups to assist in the enzymatic reaction. Examples include ATP, NAD, NADP and S-adenosylmethionine, as well as a number of vitamins, such as riboflavin (vitamin B1) and thiamine (vitamin B2). Where co-factors/co-enzymes have been identified, the Guide indicates their involvement.

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1. Overington JP, Al-Lazikani B, Hopkins AL. (2006) How many drug targets are there?. Nat Rev Drug Discov, 5 (12): 993-6. [PMID:17139284]

2. Rask-Andersen M, Masuram S, Schiöth HB. (2014) The druggable genome: Evaluation of drug targets in clinical trials suggests major shifts in molecular class and indication. Annu Rev Pharmacol Toxicol, 54: 9-26. [PMID:24016212]