Historical Perspective

The P450s were recognized and defined as a distinct class of hemoproteins only ~50 years ago. The enzymes form reduced (ferrous) iron-carbon monoxide ad-ducts in which the major heme absorption band (the Soret band) shifts to ~450 nm for the native form of the enzyme [3, 4]. Pivotal to this spectral characteristic is the axial coordination of the heme iron by a cysteine thiolate in all the P450s. The phylogenetically conserved cysteinate is termed the proximal ligand to the heme iron, with the distal ligand generally considered to be a weakly bound water molecule [5]. In early studies of P450 enzymes, two types of model system were characterized in detail. The first of these were membranous P450s derived from mammalian liver microsomes, which source their electrons from the diflavin (FAD- and FMN-containing enzyme NADPH-cytochrome P450 reductase (CPR) [6] (Fig. 5.1a). The second model system characterized from the 1960s onwards was the Pseudomonas putida camphor hydroxylase P450cam (now formally classified in the P450 gene superfamily as CYP101A1) [7]. P450cam participates in a catabolic pathway that facilitates the breakdown of camphor in the pseudomonad, and its use as a sole source of carbon for energetic requirements [8]. P450cam obtains its electrons from the iron-sulfur (2Fe-2S cluster-containing) protein putidaredoxin (Pd), which in turn sources electrons from the FAD-containing, NADH-dependent protein putidaredoxin reductase (PdR) [9, 10] (Fig. 5.1b). These two types of apparatus have come to be known as class I (CPR) and class II (PdR/Pd-type) P450 reductase systems, although (as discussed in more detail

Fig. 5.1 Protein components of class I and class II P450 redox systems. (a) Membrane-associated components of a class II P450 redox system. These are represented by the structure of mammalian CYP2C5 (PDB code 1DT6) and that of rat cytochrome P450 reductase (1AMO) [48, 146]. (b) The three components of the best-characterized class I P450 redox systems - Pseudomonas putida

Fig. 5.1 Protein components of class I and class II P450 redox systems. (a) Membrane-associated components of a class II P450 redox system. These are represented by the structure of mammalian CYP2C5 (PDB code 1DT6) and that of rat cytochrome P450 reductase (1AMO) [48, 146]. (b) The three components of the best-characterized class I P450 redox systems - Pseudomonas putida

P450cam. These are (from left) the P450 itself (CYP101A1, 1DZ6), the 2Fe-2S cluster-containing putidaredoxin (1PDX) and the FAD-binding putidaredoxin reductase (1Q1R) [5, 9, 10]. Helical and sheet segments of the proteins are distinctly colored. Bound cofactors are shown in spacefill representation: heme (red), FMN (orange), FAD (yellow) and 2Fe-2S (orange-blue)

P450cam. These are (from left) the P450 itself (CYP101A1, 1DZ6), the 2Fe-2S cluster-containing putidaredoxin (1PDX) and the FAD-binding putidaredoxin reductase (1Q1R) [5, 9, 10]. Helical and sheet segments of the proteins are distinctly colored. Bound cofactors are shown in spacefill representation: heme (red), FMN (orange), FAD (yellow) and 2Fe-2S (orange-blue)

below) far more diverse types of P450 redox systems have been identified in recent years.

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Heal Yourself With Qi Gong

Qigong also spelled Ch'i Kung is a potent system of healing and energy medicine from China. It's the art and science of utilizing breathing methods, gentle movement, and meditation to clean, fortify, and circulate the life energy qi.

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