3-Hydroxypropionic Acid

Optimal Result: 5 - 22 mmol/mol creatinine.

3-Hydroxypropionic Acid (3-HPA) is a major urinary metabolite of propionic acid. Propionic acid is derived from dietary branched-chain amino acids, oddchain fatty acids, and can be produced in the gut by bacterial fermentation of fiber. The biotin-dependent enzyme propionyl CoA carboxylase is responsible for metabolizing propionic acid to methylmalonyl CoA, which is subsequently isomerized to succinyl CoA. Decreased activity of this enzyme shunts propionyl CoA into alternative pathways which form 3-HPA.


- Tong L. Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci. 2013;70(5):863-891.

- Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM. Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency. Am J Clin Nutr. 1997;65(4):951-958.

- Surtees RAH, Matthews EE, Leonard JV. Neurologic outcome of propionic acidemia. Ped Neurol. 1992;8(5):333-337.

- Baumgartner MR, Hörster F, Dionisi-Vici C, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orph J Rare Dis. 2014;9(1):130.

- Xiong X, Liu D, Wang Y, Zeng T, Peng Y. Urinary 3-(3-hydroxyphenyl)-3-hydroxypropionic acid, 3-hydroxyphenylacetic acid, and 3-hydroxyhippuric acid are elevated in children with autism spectrum disorders. BioMed Res Int. 2016;2016.

- Chapman KA, Gropman A, MacLeod E, et al. Acute management of propionic acidemia. Mol Genet Metab. 2012;105(1):16-25.

What does it mean if your 3-Hydroxypropionic Acid result is too low?

Low levels of urinary 3-hydroxypropionic acid may be seen with decreased amino acid and fatty acid precursors from maldigestion, malabsorption or impaired fatty acid oxidation. Because the propionic acid precursor is also made in the GI tract, decreased fiber intake or antibiotic use can result in lower urinary 3-hydroxypropionic acid as well. In fact, low protein diets and antibiotics are used acutely to treat inborn errors of metabolism which cause propionic acidemia.

What does it mean if your 3-Hydroxypropionic Acid result is too high?

Biotin is a cofactor in the propionyl-CoAcarboxylase enzyme. Reduced activity of this enzyme due to functional biotin deficiency can cause elevations of the urinary organic acid 3-hydroxypropionic acid. However, in isolation, it may not be as sensitive a marker as 3-hydroxyisovaleric acid to diagnose marginal biotin deficiency.

There are inborn errors of metabolism associated with this organic acid. When the propionyl-CoA-carboxylase enzyme is deficient, the result is propionic acidemia and elevated urinary 3-hydroxypropionic acid. Some isolated case reports reveal the possibility of a later onset in this enzyme deficiency.

Because of the relationship between propionyl-CoA and methylmalonyl CoA, 3-HPA elevations have also been observed in inborn errors causing methylmalonic acidemia.

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