China
Africa
Explore chapters and articles related to this topic
Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Most CYPs are monooxygenases or mixed function oxidases, and electrons for reduction of the heme and later the oxygen substrate are provided by protein partners that bind to the face of the protein proximal to the heme (Hollenberg 1992; Iyanagi et al. 2012; Meunier et al. 2004). The heme prosthetic group is the catalytic center of the enzyme, where a reactive hypervalent oxo-iron protoporphyrin IX radical cation intermediate is formed for subsequent insertion of the iron-bound oxygen atom into a substrate bond. Substrates bind in a cavity or cleft above the surface of the heme in proximity to the reactive intermediate. The thiolate side chain of a conserved Cys residue binds to the axial coordination site of the iron opposite to the bound oxygen, giving rise to the unique spectral and functional properties of CYP enzymes. Microsomal CYPs transfer electrons from nicotinamide adenine dinucleotide phosphate (NADPH) via cytochrome P450 reductase while cytochrome b5 can also contribute reducing power to this system after being reduced by cytochrome b5 reductase (Henderson et al. 2015; Iyanagi et al. 2012; Locuson et al. 2007; Meunier et al. 2004; Pandey and Fluck 2013). Mitochondrial CYPs use adrenodoxin reductase and adrenodoxin (i.e., ferredoxin) to transfer electrons from NADPH to CYP (Neve and Ingelman-Sundberg 2010). However, CYP5A1 (thromboxane X2 synthase, TBXAS1), CYP8A1 (prostacyclin H2 synthase), and CYP74A (allene oxide synthase) do not need protein partners for their catalysis (Brash 2009). The catalytic mechanism of CYPs is similar owing to a conserved heme-thiolate functionality, but amino acid variations in the substrate binding sites confer compound selectivity, regioselectivity, and stereoselectivity of metabolism (Werck-Reichhart and Feyereisen 2000).
Gastrointestinal Function and Toxicology in Canines
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Cytochromes P450 (CYPs) are proteins of the superfamily containing the heme group as a cofactor and, therefore, are hemoproteins. CYPs use a variety of small and large molecules as substrates in enzymatic reactions. They are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term “P450” is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with carbon monoxide. CYP enzymes have been identified in all domains of life: animals, plants, fungi, protists, bacteria, archaea, and even in viruses. However, they are not omnipresent; for example, they have not been found in Escherichia coli. More than 21,000 distinct CYP proteins are known. Most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen). Based on the nature of the electron transfer proteins, CYPs can be classified into several groups: Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase (variously CPR, POR, or CYPOR). Cytochrome b5 (cyb5) can also contribute reducing power to this system after being reduced by cytochrome b5 reductase (CYB5R).Mitochondrial P450 systems, which employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450.Bacterial P450 systems, which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450.CYB5R/cyb5/P450 systems, in which both electrons required by the CYP come from cytochrome b5.FMN/Fd/P450 systems, originally found in Rhodococcus species, in which a FMN-domain-containing reductase is fused to the CYP.P450 only systems, which do not require external reducing power. Notable ones include thromboxane synthase (CYP5), prostacyclin synthase (CYP8), and CYP74A (allene oxide synthase).
Covalent immobilization of oxylipin biosynthetic enzymes on nanoporous rice husk silica for production of cis(+)-12-oxophytodienoic acid
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Thu Bao Le, Chong Soo Han, Kyoungwon Cho, Oksoo Han
Oxylipins are a group of lipid-derived signalling compounds found in both plants and animals that play important roles in defence and development. Oxylipin synthesis in plants is a multistep process initiated by the conversion of polyunsaturated fatty acids (PUFAs) into their corresponding hydroperoxides, catalyzed by lipoxygenase (LOX). One such PUFA, α-linolenic acid (LnA), is converted by LOX into 13-hydroperoxy-9,11,15-octadecatrienoic acid (HPOTE). This product is further metabolized by consecutive reactions catalyzed by allene oxide synthase (AOS) and allene oxide cyclase (AOC) to produce cis(+)-12-oxophytodienoic acid (cis(+)-12-OPDA) as part of the jasmonic acid biosynthetic pathway (Figure 1). The compound, cis(+)-12-OPDA, is a plant hormone that regulates plant growth and developmental processes [1–3]. In mammalian cells, this hormone has been shown to display cytoprotective effects [4]. Despite the importance of cis(+)-12-OPDA in both plants and animals, the in vivo regulation of oxylipin biosynthesis is difficult, due to the complicated network of signalling molecules that modulate this pathway, the unstable intermediates, and the different cellular locations of the individual enzymes required [3]. Therefore, a well-controlled in vitro synthesis of cis(+)-12-OPDA may overcome these in vivo obstacles and may benefit the agriculture and biomedicine industries.