Glyceric Acid

Optimal Result: 3.5 - 16.4 mmol/mol creatinine.

Glyceric acid is an organic acid that stems from the catabolism of the amino acid serine. Severe elevations in glyceric acid are an indication of a rare inborn error of metabolism known as glyceric aciduria. One form of glyceric aciduria is the result of a defect in the enzyme glycerate kinase which removes glyceric acid from the system. While many case studies have linked this disorder with severe developmental abnormalities, there is some debate as to whether glycerate kinase deficiency is the cause or rather a confounding variable. Another glyceric aciduria is referred to as primary hyperoxaluria type 2 (PH2). This rare genetic condition results in excessive production of oxalates in the system in the form of oxalic acid. Over time, systemic deposition of oxalates in body tissues can occur which is a process known as oxalosis. This disease is characterized by urolithiasis, nephrocalcinosis, and deposition of oxalates in other body tissues.

References:

- Rashed MS, Aboul-Enein HY, AlAmoudi M, et al. Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of glyceric acid in urine of patients with D-glyceric and L-glyceric acidurias. Biomed Chromatog. 2002;16(3):191-198.

- Van Schaftingen E. D-glycerate kinase deficiency as a cause of D-glyceric aciduria. FEBS Lett. 1989;243(2):127-131.

- Wadman S, Duran M, Ketting D, et al. D-Glyceric acidemia in a patient with chronic metabolic acedosis. Clinica Chimica Acta. 1976;71(3):477-484.

- Kalim A, Fitzsimons P, Till C, et al. Further evidence that d-glycerate kinase (GK) deficiency is a benign disorder. Brain Dev. 2017;39(6):536-538.

- Madsen RK, Lundstedt T, Gabrielsson J, et al. Diagnostic properties of metabolic perturbations in rheumatoid arthritis. Arthr Res Ther. 2011;13(1):R19.

- Yang J, Chen T, Sun L, et al. Potential metabolite markers of schizophrenia. Mol Psych. 2013;18(1):67-78.

- Kemper MJ, Conrad S, Müller-Wiefel DE. Primary hyperoxaluria type 2. Eur J Ped. 1997;156(7):509-512.

What does it mean if your Glyceric Acid result is too low?

The clinical relevance of low urinary glyceric acid has not been studied in the peer-reviewed literature. However, knowing that glyceric acid accumulation is the result of breakdown of both serine and fructose, it is possible that low glyceric acid may be caused by low amino acid status and/or low fructose intake.

What does it mean if your Glyceric Acid result is too high?

Aside from the rare inborn errors of metabolism, elevated levels of glyceric acid have been demonstrated in a few metabolomic studies. One study demonstrated that glyceric acid was among 3 metabolites that correlated in patients with rheumatoid arthritis. Furthermore, correlation between glyceric acid was amongst a small handful of metabolites that were able to effectively identify patients with schizophrenia and bipolar as compared to controls. These profiles suggest that more subtle metabolic abnormalities may result in elevated urinary glyceric acid excretion.

It is known that a deficiency in the enzyme glyoxylate reductase leads to excessive levels of glyceric acid resulting in primary hyperoxaluria type 2 and oxalosis. This enzyme requires vitamin B3 in the form of NAD as a cofactor. Whether subclinical elevations in glyceric acid could be an indication of a functional need for vitamin B3 has not been studied in the literature. Interestingly, niacin has been shown to be effective in clinical trials with patients suffering from schizophrenia. Glycerate kinase requires magnesium as a cofactor to convert glyceric acid. Therefore, magnesium deficiency may play a role in glyceric acid levels.

Lastly, glyceric acid is formed during metabolism of fructose and serine. The contribution of fructose intake to total urinary glyceric acid excretion has not been fully elucidated. A careful dietary recall should be considered with increased glyceric acid in the absence of suspected metabolic defects.

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