Food Biochemistry and Food Processing (2 edition)

BLBS102-c07 BLBS102-Simpson March 21, 2012 11:12 Trim: 276mm X 219mm Printer Name: Yet to Come

156 Part 2: Biotechnology and Enzymology

Table 7.10.The Main Enzymes Involved in Xenobiotic Metabolism

Reactions

Phase I enzymes

Cytochrome P450 (CYPs) Epoxidation/hydroxylation

N-,O-,S-dealkylation

N-,S-,P-oxidation

Desulfuration

Dehalogenation

Azo reduction

Nitro reduction

Flavin-containing monooxygenases (FMOs) N-,S-,P-oxidation

Desulfuration

Alcohol dehydrogenase Oxidation

Reductions

Aldehyde dehydrogenase Oxidation

Prostaglandin synthetase co-oxidation Dehydrogenation

N-dealkylation

Epoxidation/hydroxylation

Oxidation

Molybdenum hydroxylases Oxidation

Reductions

Esterases and amidases Hydrolysis

Epoxide hydrolase Hydrolysis

Phase II enzymes

UDP (uridine diphospho) glucuronosyl transferase

(UGT)

Glucuronide conjugation

Sulfotransferases Sulfation reaction

Sulfatases Hydrolysis of sulfate esters

Methyltransferases N-,O-,S-methylation,

GlutathioneS-transferase Alkyltransferase, aryltransferase, aralkyltransferase,

alkenetransferase, epoxidetransferase

γ-Glutamyltranspeptidase Hydrolysis

Transpeptidation

N-acetyltransferase Acetylation

Aminopeptidases Hydrolysis of peptides

N,O-Acyltransferase Acylation

Cysteine conjugateβ-lyase Methylation

Phase III enzymes

MRP (multi-drug resistance – associated protein)

MDR (multi-drug resistance family/P-glycoprotein)

MXR (mitoxantrone-resistance protein) efflux

Transport and excretion of soluble products from phase I and II

metabolic pathways

Source:Rommel and Richard 2002, Hodgson 2004, Josephy and Mannervik 2006.

risk of developing papillary thyroid cancer in Middle Eastern

population (Siraj et al. 2008).

Another studied genetic polymorphic enzyme is superoxide

dismutase-2 (SOD). The heterozygosity 9Val-allele of MnSOD

is associated with a higher risk and severity of orofaciolin-

gual dyskinesias (TDof) in Russian psychiatric inpatients from

Siberia (Al Hadithy et al. 2010). In addition, there are several

studies that have reported and showed that the 9Val/9Val geno-

type confer great susceptibility to tardive dyskinesia (Zhang

et al. 2003, Akyol et al. 2005, Galecki et al. 2006, Hitzeroth

et al. 2007). In addition, human MnSOD gene encoding alanine

(A) or valine at codon 16 (Shimoda-Matsubayashi et al. 1996)

can be a risk factor for several malignancies (Iguchi et al. 2009).

Phase II

Polymorphisms of human UGT correlate with diseases and side

effects of drugs, for example the isoform UGT1A1 is asso-

ciated with diseases of bilirubin metabolism (Hodgson 2004).

N-Acetyltransferases (NAT) are important enzymes that par-

ticipate in metabolic activation of carcinogenic aromatic and

heterocyclic amines that are present in cigarette smoke (Wang