Fig. 1: Biochemical pathway and cross-species conservation of BBOX1/GBH-1.
From: Biallelic variants in BBOX1 cause L-Carnitine deficiency and elevated γ-butyrobetaine
A L-Carnitine Biosynthesis Pathway: Four steps of the L-carnitine biosynthesis pathway, catalyzed by respective conserved orthologous enzymes in humans (Hs) and C. elegans (Ce), ended by the production of L-carnitine by BBOX1/GBH-1; Pathway was generated and adapted from MetaCyc database28 (https://metacyc.org/pathway?orgid=META&id=PWY-6100&ENZORG=TAX-9606&detail-level=3). B Patient pedigrees; C BBOX1/GBH-1 sequence conservation and variant modeling. The sequence alignment suggests the conservation of the BBOX1 across various species, including humans, mice, zebrafish, fruit flies, and C. elegans (GBH-1) (from top to bottom). The positions of amino acid residues altered in patient-derived variants are invariant. CRISPR/Cas9-assisted gene editing in C. elegans models the human variants p.Asp59Gly, p.Gly263Arg, and p.Gly227Valfs*6, corresponding to D59G, G283R, and G247Vfs*6 in GBH-1, to examine their impact on the function of the L-carnitine biosynthesis pathway.
