Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

Abstract

Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients’ quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases.

Cytochrome P450 Enzymes and Drug Metabolism in Humans

“…In addition to smoking, some dietary chemicals may regulate the catalytic activity of CYPs. For example, an increase of unsaturated fatty acids in food can enhance the expression of CYPs in the liver [ 80 ], and lacking protein, vitamin C, calcium, or magnesium in food may reduce the activity of CYPs in the process of metabolizing some drugs [ 81 , 82 , 83 ]. CYP3A can be induced by some brassicaceous vegetable, such as turnips and spinach, causing the enhancement of the first-pass effect of phenacetin [ 84 ].…”

Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A2

“…Four regio-isomeric EETs (5,8,11, under both physiological and pathological conditions (Karara et al, 1991). A high regio-and stereoselectivity has also been observed when testing the effects of chemically synthesized epoxides from AA and EPA in renal arteries (Karara et al, 1991;Lucas et al, 2010;Sarparast et al, 2020). Each regioisomer can exist as S/R-and R/S-enantiomers, and both the production and vascular activity of these enantiomers can vary between vascular beds and species (Karara et al, 1991;Lucas et al, 2010).…”

Relationship between Nutrition, Lifestyle, and Neurodegenerative Disease: Lessons from ADH1B, CYP1A2 and MTHFR

“…Concerning the four SNPs of interest and the disease-related factors, cognitive impairment (SNPs of APOE , ADH1B , MTHFR ), alcohol abuse ( ADH1B variant), caffeine consumption (SNPs of CYP2A1 , MTHFR ), and homocysteine levels ( MTHFR variant) appeared as the mostly represented traits. Indeed, this result reflects the biological functions of these genes in human health and disease and point to ADH1B , CYP1A2, and MTHFR as candidate nutrigenomic factors able to influence the susceptibility and progression to NDDs [ 61 , 62 , 63 ]. Moreover, these genes and their related variants deserve further investigation because of their possible application to optimize and personalize the treatment to such conditions.…”