Table 3.
Many of the heavily studied major classes of human enzymic metabolism genes
| Mechanism | Encoded enzymes (gene root symbols, where applicable) | Families, classes, groups* | Representative reference(s) |
|---|---|---|---|
| Oxidation | |||
| Hydroxylases | Dozens of classes; > 1000 genes in genome | [295, 296] | |
| CYP monooxygenases (CYP; P450s) | Total of 18 families; 57 genes in human genome versus 102 in mouse | [206, 213, 297] | |
| CYP1 (3 in Homo; 3 in Mus) | [206] | ||
| CYP2 (16 in Homo; 50 in Mus) | [206] | ||
| CYP3 (4 in Homo; 9 in Mus) | [206] | ||
| CYP4 (12 in Homo; 20 in Mus) | [206] | ||
| CYP5, 7, 8, 11, 17, 19, 20, 21, 24, 26, 27, 39, 46, 51 | [213] | ||
| Flavin-dependent monooxygenases (FMO) | 6 genes | [298, 299] | |
| Alcohol dehydrogenases (ADH) | 8 genes | [300, 301] | |
| Aldehyde dehydrogenases (ALDH) | 11 families, 4 subfamilies, 19 genes | [302, 303] | |
| Lysine (histone) demethylases (KDM) | 8 groups; 24 genes | [304, 305] | |
| Monoamine oxidases (MAO) | Two genes | [306] | |
| Other amine oxidases | > 50 genes | [307] | |
| Peroxidases (PEX) | > 30 genes | [308, 309] | |
| Catalase | Three main groups; one gene in human | [310, 311] | |
| Oxidoreductases | < 40 genes, subunits | [312, 313] | |
| Reduction | |||
| CYP reductive reactions (CYP) | CYP1, 2, 3, and 4 families | [314] | |
| NADPH-quinone oxidoreductases (NQO) | Two genes | [315] | |
| Aldo-keto reductases (AKR) | Two families, 7 subfamilies, 19 genes | [316] | |
| Carbonyl reductases (CBR) | Three genes | [316, 317] | |
| Short-chain dehydrogenases/reductases (SDR) | Up to 77 protein-coding genes | [318] | |
| Oxidoreductases | > 50 | [318, 319] | |
| Hydrolysis | |||
| Epoxide hydrolases (EPHX) | Up to 7 genes | [320, 321] | |
| Amidases | Three genes | [322] | |
| Esterases | At least 8 genes | [323, 324] | |
| Lipases (LIP) | 22 genes | [325] | |
| Conjugation | |||
| UDP glucuronosyltransferases (UGT) | 4 families; 5 subfamilies; 23 genes† | [326, 327] | |
| Glutathione S-transferases (GST) | 8 families; 21 genes | [328] | |
| Soluble sulfotransferases (SULT) | 4 families; 9 subfamilies; 14 genes | [329] | |
| Membrane-bound sulfotransferases | 37 genes | [330] | |
| N-acetyltransferases (NAT) | 26 genes; two groups; GCN5-related (24 genes) and arylamine-related (2 genes) | [331, 332] | |
| Other transferases | Up to 41 groups; 265 protein-coding genes | HGNC | |
*Virtually all these enzyme classes, and members of each gene group with their chromosomal locations, can be found in genenames.org (HGNC)
†The “number of UGT genes” is debatable, because of the complex structures of the UGT1 and UGT2 loci
Details of the CYP gene family are perhaps the most studied on this list. The mammalian CYP2, CYP3, and CYP4 families each have many genes encoding plant-metabolizing enzymes, and the number of genes in each family varies widely among mammals [206]. The CYP1 family is involved in some plant-metabolizing enzymes but also arachidonic acid pathway-associated lipid mediator substrates [333], steroids, pigments, polycyclic aromatic hydrocarbons, polyhalogenated biphenyls, etc. The remaining 14 CYP families encode evolutionarily highly conserved enzymes with much more highly specific endogenous substrates (ablation of many or most of these is lethal), and the number of genes in each family is virtually identical among all mammalian genomes [213, 334]