A novel pyrroline-5-carboxylic acid and acetoacetic acid adduct in hyperprolinaemia type II

Walker, Valerie, Mills, Graham A., Mellor, John M., Langley, G. John and Farrant, R. Duncan (2003) A novel pyrroline-5-carboxylic acid and acetoacetic acid adduct in hyperprolinaemia type II. Clinica Chimica Acta, 331 (1-2), 7-17. (doi:10.1016/S0009-8981(03)00077-9).

Abstract

Background: From investigations of a child with hyperprolinaemia type II, we demonstrated in vitro that pyridoxal phosphate forms a novel adduct with a proline metabolite, pyrroline-5-carboxylic acid, through Claisen condensation. Studies indicated that this was a previously unsuspected generic reaction of aldehydes and some ketones. We have subsequently found the acetoacetic acid adduct in both plasma and urine from the affected child.
Methods: Mixtures of acetoacetic acid and pyrroline-5-carboxylic acid were co-incubated at pH 7.4 and 37 C, dried, or extracted and dried, derivatised and analysed by gas chromatography/mass spectrometry (GC/MS). Urine and plasma from the child were analysed.
Results: Fourteen new peaks were found in derivatised pyrroline-5-carboxylic acid/acetoacetic acid co-incubates. From accurate molecular mass data, the four largest peaks were probably diastereoisomers of tri-trimethylsilyl (tri-TMS) derivatives of alcohol adducts formed by Claisen condensation. Eight other peaks were mono- and di-trimethylsilyl derivatives of the adduct and a decarboxylated product. The adduct was demonstrated unequivocally in the child's acute urine and traces in plasma.
Conclusions: Pyrroline-5-carboxylic acid forms an adduct with acetoacetic acid, which was present in urine of a sick child with hyperprolinaemia type II. Evidence suggests it formed in vivo. The biological significance of this novel reaction of aldehydes and ketones merits investigation.

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Contributors

Author: G. John Langley

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