Limonin metabolism

A. Hasegawa, S. Metabolism of limonoids Limonin D-ring lactone hydrolase activity in Pseudomonas. J. Agri. Food Chem., 1976, 2A, 2A-26. 

Biosynthesis and metabolism of limonin and its closely related limonoids... 

Limonin appears to be the predominant end product of the limonin pathway. However, some limonin is further metabolized to 17-dehydrolimonoate A-ring lactone (7), deoxylimonin (8), limonol (9) and other compounds (18-21). These metabolites are all nonbitter and only occur in seeds in low amounts. 

Specific target enzymes Based on the metabolic and catabolic pathways of limonin in Citrus, several enzymes have been identified for possible genetic manipulation. Specifically, we are currently looking at three enzyme systems 1) limonoate dehydrogenase, 2) limonin UDP-D-glucose transferase and 3) nomilin deacetylase. 

Limonoid UDP-D>glucose transferase Limonin bitterness is a problem in juices extracted from early-season to mid-season winter fruit, but not a problem in juice extracted from the late season fruit. As the fruit ripens, the concentration of limonoate A-ring lactone (2) decreases (23,24). This natural limonin debittering process has been known for over a century, but the mechanism of this metabolism was not understood until the recent discovery that limonoid glucosides are present in mature fruit tissues and seeds. We observed that in navel orange the initial... 

Mechanism-based inhibition of the drug-metabolizing isoenzyme CYP3A4 was observed in human liver microsomes treated with the compounds rutaecarpine or limonin, with activity reported as preincubation time dependent (Iwata et al. 2005). 

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