Two new sulphur-containing amino acids in man

Area of Science:

• Biochemistry
• Metabolic Disorders
• Clinical Chemistry

Background:

• A severe case of infant mortality presented with major physical malformations and developmental failure.
• Unusual sulfur-containing amino acids were detected in the patient's urine, prompting further investigation.

Purpose of the Study:

• To identify and characterize novel sulfur-containing amino acids found in infant urine.
• To investigate the metabolic origin of these compounds and their potential link to the observed malformations.

Main Methods:

• Isolation and identification of urinary compounds using sensitive mass spectrometry.
• Radiolabeling studies using [14C]Valine and [35S]cysteine in fibroblast cultures.
• Analysis of metabolic pathways involving cysteine conjugation and decarboxylation.

Main Results:

• Two novel sulfur-containing amino acids, S-(2-carboxypropyl)-cysteine and S-(2-carboxypropyl)-cysteamine, were identified.
• Radioactive labeling confirmed the origin of these compounds from the conjugation of methacrylic acid with cysteine.
• Findings suggest a potential deficiency in methacrylyl-CoA hydratase, an inborn error of metabolism.

Conclusions:

• The identified amino acids and parental consanguinity strongly suggest a new inborn error of methacrylyl-CoA hydratase.
• Methacrylic acid or its derivatives are implicated as a potential cause of the infant's severe congenital malformations.