Drug metabolism conjugation

Han TH, Zhao B. ADME considerations for the development of antibody-drug conjugates. Drug Metabolism and Disposition The Biological Fate of Chemicals. 2014 42 1914-20. 

Guyan et al. 1990) have used several markers of lipid peroxidation (9-cis-, 11-tmns-isomer of linoleic acid, conjugated dienes and ultraviolet fluorescent products) to demonstrate significant increases in the duodenal aspirate after secretin stimulation in patients with acute and clinic pancreatitis. They interpreted this as indicating induction of hepatic and pancreatic drug-metabolizing enzymes in the face of a shortfidl of antioxidant defences, more marked in chronic pancreatitis. Subsequent studies in patients with chronic pancreatitis have confirmed decreased serum concentrations of selenium, -carotene and vitamin E compared with healthy controls (Uden et al., 1992). Basso aol. (1990) have measured increases in lipid peroxides in the sera of patients with chronic... 

Testa B (2006) Principles of drug metabolism 2 hydrolysis and conjugation reactions. In Taylor JB, Triggle DJ (eds) Comprehensive medicinal chemistry II. Elsevier, Oxford, Sect 5.06... 

Jakokby, W.B. (1981). Detoxification and drug metabolism conjugation and related systems. In Methods in Enzymology, Vol. 77. Academic Press, New York... 

Another study by McChesney and co-workers on the metabolism of nalidixic acid in the immature calf(23) demonstrated a pattern of metabolism very different than in man. The half-life of nalidixic acid was found to be about 24 hours and a large amount was excreted into the feces. The immature calves were also unable to excrete nalidixic acid into the urine at concentrations greater than found in the plasma and conjugated drug was present at low levels only. Calves seven months old had metabolic patterns much closer to man the plasma half-life was about 1.5 hours, the concentration of excretion into the urine was at least ten times that in plasma and the extent of conjugation was increased. The inability to metabolize nalidixic acid by the immature calf was considered to be due to incomplete development of its metabolic system. 

Conjugation Reactions in Drug Metabolism , Ed. G. J. Mulder, Taylor Francis, London, 1990. 

Conjugation-Deconjugation Reactions in Drug Metabolism and Toxicity , Ed. F. C. Kauffman, Springer Verlag, Berlin, 1994. 

B. Ketterer, The Role of Nonenzymatic Reactions of Glutathione in Xenobiotic Metabolism , Drug Metab. Rev. 1982, 13, 161 - 187 B. Ketterer, G. J. Mulder, Glutathione Conjugation , in Conjugations Reactions in Drug Metabolism , Ed. G. J. Mulder, Taylor and Francis, London, 1990, p. 307 - 364. 

Gietl YS, Anders MW. 1991. Biosynthesis and biliary excretion of S-conjugates of hexachlorobuta-1,3-diene in the perfused rat liver. Drug Metabolism and Disposition 19 274-277. 

Kauffman FC (1994) Conjugation-deconjugation reactions in drug metabolism and toxicity. 

Put very simply two sorts of drug-metabolizing enzymatic processes occur in the microsomes of the smooth endoplasmic reticulum or in the cytosol of liver cells. The first, so-called Phase F, reactions may add or subtract a small portion of the drug molecule, commonly by oxidation. This by itself may make a product more water-soluble, but, more commonly, a second step - Phase IF- process is required in which the altered drug is coupled (conjugated - literally married ) to compounds already existing in the liver cells to form salts such as glu-curonides and sulphates (Fig. 3). 

Phase II conjugative enzymes metabolize drugs by attaching (conjugating) a more polar molecule to the original drug molecule to increase water solubility,... 

---