Metabolism of phenolics in coffee and plant-based foods by canonical pathways: an assessment of the role of fatty acid β-oxidation to generate biologically-active and -inactive intermediates

Abstract

ω-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with ω-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous β-oxidation. 3′,5′-Dihydroxy-derivatives (from alkyl-resorcinols, flavanols, proanthocyanidins), and 4′-hydroxy-phenolic acids (from tyrosine, p-coumaric acid, naringenin) are β-oxidation substrates yielding benzoic acids. In contrast, 3′,4′,5′-tri-substituted-derivatives, 3′,4′-dihydroxy-derivatives and 3′-methoxy-4′-hydroxy-derivatives (from coffee, tea, cereals, many fruits and vegetables) are poor β-oxidation substrates with metabolism diverted via gut microbiota dehydroxylation, phenylvalerolactone formation and phase-2 conjugation, possibly a strategy to conserve limited pools of coenzyme A. 4′-Methoxy-derivatives (citrus fruits) or 3′,4′-dimethoxy-derivatives (coffee) are susceptible to hepatic “reverse” hydrogenation suggesting incompatibility with enoyl-CoA-hydratase. Gut microbiota-produced 3′-hydroxy-4′-methoxy-derivatives (citrus fruits) and 3′-hydroxy-derivatives (numerous (poly)phenols) are excreted as the phenyl-hydracrylic acid β-oxidation intermediate suggesting incompatibility with hydroxy-acyl-CoA dehydrogenase, albeit with considerable inter-individual variation. Further investigation is required to explain inter-individual variation, factors determining the amino acid to which C6–C3 and C6–C1 metabolites are conjugated, the precise role(s) of l-carnitine, whether glycine might be limiting, and whether phenolic acid-modulation of β-oxidation explains how phenolic acids affect key metabolic conditions, such as fatty liver, carbohydrate metabolism and insulin resistance.