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1.

Cytochrome P450 - arranged by substrate type

The P450 isozyme system is the major phase 1 biotransforming system in man, accounting for more than 90% of drug biotransformations. This system has huge catalytic versatility and a broad substrate specificity, acting upon xenobiotica and endogenous compounds. It is also called the...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
2.

Phase 1 - Functionalization of compounds

Phase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
3.

Endogenous sterols

A number of CYPs take part in cholesterol biosynthesis and elimination, thus playing an important role in maintaining cholesterol homeostasis. Under normal physiological conditions, cholesterol intake (diet or synthesized de novo from acetyl CoA) equals cholesterol elimination (degraded...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
4.

Xenobiotics

Of the 50 microsomal CYPs, 15 act on xenobiotics. They all possess wide substrate specificity to cater for most foreign compounds that find their way into the body.

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
5.

Biological oxidations

All organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ingestion but inhalation and transdermal routes are also common.The very nature of...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
6.

Fatty acids

The CYP4 family are the main CYPs involved in the metabolism of long-chain fatty acids.

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
7.

Steroid hormone biosynthesis

Steroid hormones derived from cholesterol are a class of biologically active compounds in vertebrates. The cholesterol side-chain cleavage enzyme CYP11A1 catalyzes conversion of cholesterol, a C27 compound, to the first C21 steroid, pregnenolone, which is converted by a bifunctional...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
8.

Metabolism of steroid hormones

Steroid hormones are synthesized primarily in the adrenal gland and gonads. They regulate energy metabolism and stress responses (glucocorticoids), salt balance (mineralocorticoids), and sexual development and function (androgens and estrogens). All steroids are synthesized from cholesterol....

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
9.

CYP2E1 reactions

CYP2E1 can metabolize and activate a large number of solvents and industrial monomers as well as drugs. This quality of CYP2E1 may make it an important determinant of human susceptibility to the toxic effects of industrial and environmental chemicals. Typical CYP2E1 substrates include...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
10.

Arachidonic acid metabolism

Eicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth muscle contraction and relaxation, and the release of gastric acid. Eicosanoids are...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
11.

Miscellaneous substrates

Approximately a quarter of the 57 human CYPs still remain "orphans" in the sense that their function, expression sites, and regulation are largely not elucidated. While there is enough experimental evidence to know that all these proteins get made and can catalyze CYP-like reactions...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
12.

Eicosanoids

Arachidonic acid is metabolized via three major enzymatic pathways: cyclooxygenase, lipoxygenase, and cytochrome P450. The cytochrome P450 pathway metabolites are oxygenated metabolites of arachidonic acid.

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
13.

Glucocorticoid biosynthesis

Cortisol, the major human glucocorticoid, is synthesized in the zona fasciculata of the adrenal cortex from pregnenolone. Pregnenolone is converted to 17alpha-hydoxyprogesterone in two reactions, both catalyzed by 3-beta-hydroxysteroid dehydrogenase/isomerase. 17Alpha-hydroxyprogesterone...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
14.

Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)

Similar to the lipoxygenases, cytochrome P450 (CYP) enzymes catalyse the hydroxylation and epoxygenation of arachidonic acid. However, whereas lipoxygenases use an active non-heme iron to abstract hydrogen directly from arachidonic acid, CYPs contain a heme-iron active site that...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
15.

Metabolism of xenobiotics by cytochrome P450

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
16.

Chemical carcinogenesis

It has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens act through a variety of genotoxic and non-genotoxic mechanisms. Genotoxic carcinogens...

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
17.

C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone

Pathway module; Carbohydrate and lipid metabolism; Sterol biosynthesis

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
18.

C21-Steroid hormone biosynthesis, progesterone => corticosterone/aldosterone

Pathway module; Carbohydrate and lipid metabolism; Sterol biosynthesis

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
19.

Arachidonic acid metabolism

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens
20.

Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)

The epoxidation of arachidonic acid by cytochrome P450s (CYPs) results in the formation of unique bioactive lipid mediators termed epoxyeicosatrienoic acids (EETs). Each double bond has been shown to be susceptible to oxidation, resulting in 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET....

Type
:
pathway
Taxonomic scope
:
organism-specific biosystem
Organism
:
Homo sapiens

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