Unknown enzyme(s) process 4-HMA to 4-Hbz

Stable Identifier
R-HSA-9856737
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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Unknown enzyme(s) process 4-HMA to 4-Hbz
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It is unknown how (S)-4-hydroxymandelate (4-HMA) gets processed to 4-hydroxybenzaldehyde (4-HBz). In yeast, the dehydrogenases DLD1 and DLD2 were shown to be necessary for these step(s) (Valera et al., 2020; reviewed in Fernández-del-Río & Clarke, 2021). In humans, the closest homologs of DLD1/2 are mitochondrial LDHD and D2HGDH whose known functions are in D-malate and D-lactate metabolism (Yang et al., 2021; Jin et al., 2023). Hypothetically, they could dehydrogenate 4-hydroxymandelate to 4-hydroxybenzoylformate (4-HBF, 4-hydroxyphenylglyoxylate), and in a second step 4-HBF would be decarboxylated by an unknown enzyme to 4-HBz. Alternatively, 4-HMA could be directly decarboxylated in one step to 4-HBz (Husain et al., 2020; reviewed in Staiano et al., 2023).
Literature References
PubMed ID Title Journal Year
32561586 The Mandelate Pathway, an Alternative to the Phenylalanine Ammonia Lyase Pathway for the Synthesis of Benzenoids in Ascomycete Yeasts

Valera, MJ, Boido, E, Ramos, JC, Manta, E, Radi, R, Dellacassa, E, Carrau, F

Appl Environ Microbiol 2020
34198496 Coenzyme Q Biosynthesis: An Update on the Origins of the Benzenoid Ring and Discovery of New Ring Precursors

Fernández-Del-Río, L, Clarke, CF

Metabolites 2021
37508007 Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

Staiano, C, García-Corzo, L, Mantle, D, Turton, N, Millichap, LE, Brea-Calvo, G, Hargreaves, I

Antioxidants (Basel) 2023
37863926 Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis

Jin, S, Chen, X, Yang, J, Ding, J

Nat Commun 2023
33431826 Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations

Yang, J, Zhu, H, Zhang, T, Ding, J

Cell Discov 2021
34471290 The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway

Banh, RS, Kim, ES, Spillier, Q, Biancur, DE, Yamamoto, K, Sohn, ASW, Shi, G, Jones, DR, Kimmelman, AC, Pacold, ME

Nature 2021
Participants
Input
Output
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Catalyst Activity

carboxy-lyase activity of Unknown carboxylyase [mitochondrial matrix]

Physical Entity
Unknown carboxylyase [mitochondrial matrix] (Homo sapiens)
Activity
carboxy-lyase activity (GO:0016831)
Authored
Stephan, R  (2023-12-22)
Reviewed
Pierrel, F  (2024-05-02)
Marchi, M  (2024-05-14)
Tonello, F  (2024-05-15)
Hill, DP  (2025-08-12)
Created
Stephan, R  (2023-12-22)
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