Skip to main content
Fig. 8 | Orphanet Journal of Rare Diseases

Fig. 8

From: Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency

Fig. 8

Potential mechanisms leading to biomarker abnormalities in SSADHD patients. The pathway of GABA metabolism is shown, with X indicating the site of the block in patients with SSADHD. This results in accumulation of GHB, in addition to GABA and succinic semialdehyde (SSA). Under physiological conditions, GABA can undergo lactonization to form the internal γ-lactam, 2-pyrrolidone (2-pyr [12];). Structural similarities of 2-pyr with the imidazole/pyrrolidine structures of crn, pro and his may associate with alterations in EA, sarc, gly, guac, crn, figlu and pro. Brown et al. [1] first proposed that 4,5-dihydroxyhexanoate (4,5-DHHA; also solerole (sol)) derived from accumulated SSA and an “active” 2-carbon fragment (acetyl-CoA, or the acyl- moiety of pyruvic acid). 4,5-DHHA can undergo internal lactonization to at least two species in relation to its vicinal hydroxyl- groups, one of which is solerole. A potential combination of accumulated 4,5-DHHA, sol, SSA or GHB may result in interference with the distal portion of tyrosine metabolism at the level of 4-maleylacetoacetate (4-MAA) and/or fumarylacetoacetate (FA), resulting in decreased Suac. Dashed lines indicate proposed pathways of interference/inhibition

Back to article page
\