Organic Acids, Comprehensive, Quantitative, Urine [Quest Diagnostics]

4-Hydroxyphenylpyruvic

Optimal Result: 0 - 6 mmol/mol creatinine.

Other names: 4-Hydroxyphenylpyruvate, 4-HPPA

4-hydroxyphenylpyruvic acid is an intermediate in the breakdown of phenylalanine.

4-hydroxyphenylpyruvic acid is converted to homogentisate; a blockage at this step results in increased homogentisate, which can be diagnostic of alkaptonuria.

If the pathway is not blocked, 4-HPPA ends up in the Krebs cycle converted into fumaric acid.

4-Hydroxyphenylpyruvic acid (4-HPPA) is a keto acid. It is a product of the enzyme (R)-4-hydroxyphenyllactate dehydrogenase and is formed during tyrosine metabolism.

Tyrosine can be metabolized to produce hormones such as thyroxine and triiodothyronine or it can be metabolized to produce neurotransmitters such as L-DOPA, dopamine, adrenaline, or noradrenaline. Tyrosine can also serve as a precursor of the pigment melanin and for the formation of Coenzyme Q10.

There are two isomers of HPPA, specifically 4HPPA and 3HPPA, of which 4HPPA is the most common. The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD is known to lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been shown that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency.

References:

PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Pathway Summary for Pathway SMP0000006, Tyrosine Metabolism, Source: PathBank; [cited 2023 May 24]. Available from: https://pubchem.ncbi.nlm.nih.gov/pathway/PathBank:SMP0000006

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