Metabolism of Prostaglandins

Earlier studies on the metabolism of PG s have revealed that they are metabolized largely by (i) oxidation of the allylic C-15 OH-group, (ii) reduction of the A -double bond, (iii) tu-hydroxylation and co-oxidation, and (iv) one or two steps of /S-oxidation of the original C,-carboxylic side-chain. In the human, PGEa and PGFag were found to be metabolized mainly to the Cj, 9,10-dihydro-ll-oxo-diacids (217) and (218), respectively. Several 

Urinary metabolites of Fg have also been investigated in the guinea-pig, the rat, and the rabbit, and of the metabolites found in human urine only three have been found elsewhere—(218) in the rat and rabbit, (226) in the rabbit, and (223) in the rat. Additional metabolites of Fga found in rabbit 

Hamberg and Samuelsson have published full details on the structure of the main urinary metabolite of PCEj and PGEg in guinea-pig, which was determined as (235). The main urinary metabolite of PGEg in the rat was 

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Aitken AE, Roman LJ, Loughran PA, et al. Expressed CYP4A4 metabolism of prostaglandin E(l) and arachidonic acid. Arch Biochem Biophys 2001 393(2) 329-338. 

During cooxidation, some substrates are activated to become more toxic than they were originally. In some cases substrate oxidation results in the production of free radicals, which may initiate lipid peroxidation or bind to cellular proteins or DNA. Another activation pathway involves the formation of a peroxyl radical from subsequent metabolism of prostaglandin G2. This reactive molecule can epoxidize many substates including polycyclic aromatic hydrocarbons, generally resulting in increasing toxicity of the respective substrates. 

Fatty acid w-hydroxylation is involved in the.metabolism of prostaglandins and leukotrienes, and is the first step of dicarboxylic acid formation in the cell. In this assay, lauric acid is hydroxylated to form 12-hydroxylauric acid, which is then fluorescence-labeled on the carboxyl group with 3-bromomethyl-7-methoxy-l,4-benzoxazin-2-one. 

Kozak KR, Crews BC, Ray JL, Tai HH, Morrow JD, Marnett LJ (2001) Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in vitro and in vivo. J Biol Chem 276 36993-36998... 

Appreciation of capillary columns is shown in the most recent papers. As noted by Fitzpatrick [472], many different metabolites originating from arachidonic acid may occur in various samples. Thus, sample complexity appears to be a major deterrent to clarification of the metabolism of prostaglandins and thromboxanes. Impressive chromatograms were shown in glass capillary colunms connected to both the electron capture detector [458,464] and a mass spectrometer [459,469]. Fig. 3.24 seems representative of the recent advances in this area. Moreover, it has been noted [469] that capillary columns may also provide superior quantitation. 

Fletcher, J.R. and Ramwell, P.W. (1977). Altered lung metabolism of prostaglandins during hemorrhagic and endotoxin shock. Surg. Forum, 28, 184-186... 

Diczfalusy, U., Kase, B.F., Alexson, S.E. Bjorkhem, I. (1991) J. Clin. Invest. 8 978-984. Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importanee for in vivo degradation of prostaglandins in humans. 

Monooxygenase metabolism of prostaglandins and essential fatty acids... 

A number of studies on the occurrence, release, and metabolism of prostaglandins and their role in gastric secretion and gastrointestinal motility have been completed or are in progress.52 The implication of CAMP in their mode of action remains of interest, and this topic has been the subject of recent reviews. ... 

Sampling of biological fluids (blood, urine, amniotic fluid, etc. ..) or tissues should be carried out according to a standard procedure adapted for each biological medium. Biosynthesis and metabolism of prostaglandins in the sample must be inhibited. In the case of urine, for example, each miction was collected in a clean vessel and immediately transferred to a bottle at 4 C containing meclofenamic acid. The total volume was measured after 24 hours and a fraction stored at -20 C. 

Granstrem E, Sairoielsson B On tlie metabolism of prostaglandin F2a in female subjects. J Btot Chm 246 5254, 1971. 

Sun FF, Stafford JE Metabolism of prostaglandin 2 in Rhesus monkeys. BtochMn Biophy Acta 369 95, 1974. 

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