Acylpeptide hydrolase (APEH) sequence variants with potential impact on the metabolism of the antiepileptic drug valproic acid.

Acylpeptide hydrolase (APEH) is a serine protease involved in the recycling of amino acids from acylated peptides. Beyond that, APEH participates in the metabolism of the antiepileptic drug valproic acid (2-propylpentanoic acid; VPA) by catalyzing the hydrolysis of the VPA metabolite valproylglucuronide (VPA-G) to its aglycon. It has been shown that the inhibition of APEH by carbapenem antibiotics decreases therapeutic VPA levels by enhancing the urinary elimination of VPA in form of VPA-G.

Novel patient missense mutations in the HSD17B10 gene affect dehydrogenase and mitochondrial tRNA modification functions of the encoded protein.

MRPP2 (also known as HSD10/SDR5C1) is a multifunctional protein that harbours both catalytic and non-catalytic functions. The protein belongs to the short-chain dehydrogenase/reductases (SDR) family and is involved in the catabolism of isoleucine in vivo and steroid metabolism in vitro. MRPP2 also moonlights in a complex with the MRPP1 (also known as TRMT10C) protein for N1-methylation of purines at position 9 of mitochondrial tRNA, and in a complex with MRPP1 and MRPP3 (also known as PRORP) proteins for 5'-end processing of mitochondrial precursor tRNA.