p-Hydroxyphenylacetic acid, also known as 4-hydroxybenzeneacetate, is classified as a member of the 1-hydroxy-2-unsubstituted benzenoids. 1-Hydroxy-2-unsubstituted benzenoids are phenols that are unsubstituted at the 2-position. p-Hydroxyphenylacetic acid is considered to be slightly soluble (in water) and acidic. p-Hydroxyphenylacetic acid can be synthesized from acetic acid. It is also a parent compound for other transformation products, including but not limited to, methyl 2-(4-hydroxyphenyl)acetate, ixerochinolide, and lactucopicrin 15-oxalate. p-Hydroxyphenylacetic acid can be found in numerous foods such as olives, cocoa beans, oats, and mushrooms. p-Hydroxyphenylacetic acid can be found throughout all human tissues and in all biofluids. Within a cell, p-hydroxyphenylacetic acid is primarily located in the cytoplasm and in the extracellular space. p-Hydroxyphenylacetic acid is also a microbial metabolite produced by Acinetobacter, Clostridium, Klebsiella, Pseudomonas, and Proteus. Higher levels of this metabolite are associated with an overgrowth of small intestinal bacteria from Clostridia species including C. difficile, C. stricklandii, C. lituseburense, C. subterminale, C. putrefaciens, and C. propionicum. l-tyrosine, derived from diet and endogenous proteins and peptides, can be converted to phenol and 4-hydroxyphenylpyruvate. Tyrosine phenol-lyase (EC 4.1.99.2.), previously named β–tyrosinase, is responsible for the reversible deamination of l-tyrosine, requiring pyridoxyl phosphate as a cofactor, into phenol ammonia and pyruvate. This reaction is also reversible by the same enzyme using l-serine and phenol as substrates. In addition, the reversible reaction of l-tyrosine with 2-oxoglutarate in 4-hydroxyphenylpyruvate and L-glutamate is catalysed by tyrosine transaminase (EC 2.6.1.5.) or by aromatic-amino-acid transaminase (EC 2.6.1.57.). To a small extent, 4-hydroxyphenylpyruvate and ammonia can also be formed by the enzyme phenylalanine dehydrogenase (EC 1.4.1.20.) from l-tyrosine. -Hydroxyphenylpyruvate is the precursor of 4-hydroxyphenylacetate, catalysed by p-hydroxyphenylpyruvate oxidase (EC 1.2.3.13.).

Metabolism and Physiological Effects of 4-Hydroxyphenylacetic acid References