HPDL dioxygenates HPPA

Stable Identifier
R-HSA-9856718
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Mitochondrial 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) was shown to process 4-hydroxphenylpyruvate (HPPA) to (S)-4-hydroxymandelate (4-HMA). HPDL defects lead to CoQ10 deficiency, and the HPDL product 4-hydroxymandelate apparently is a precursor for the synthesis of 4-hydroxybenzoate, which is a prerequisite for the assembly of the CoQ10 head group (Banh et al., 2021). Because HPDL is a mitochondrial protein, cytosolic HPPA from tyrosine catabolism must be imported by an unknown transport mechanism (Husain et al., 2020; reviewed in Staiano et al., 2023).
Literature References
PubMed ID Title Journal Year
32707086 Bi-allelic HPDL Variants Cause a Neurodegenerative Disease Ranging from Neonatal Encephalopathy to Adolescent-Onset Spastic Paraplegia

Bakhtiari, S, Brandl, U, Meitinger, T, Sturm, M, Kobeleva, X, Ghasemi Firouzabadi, S, Husain, RA, Krageloh-Mann, I, Mane, S, Riess, O, Hübner, CA, Bolduc, F, Deschauer, M, Feichtinger, RG, Döbler-Neumann, M, Hennings, JC, Klopstock, T, Beck-Woedl, S, Grimmel, M, Rostásy, K, Strom, TM, Laugwitz, L, Bevot, A, Darvish, H, Mayr, JA, Nägele, T, Huebner, AK, Ng, AC, Besse, A, Kruer, MC, Saadi, A, Marx, C, Bonnen, PE, Klockgether, T, Colleaux, L, Hartmann, H, Chiang, D, Radelfahr, F, Wortmann, SB, Haack, TB, Buchert, R, Tafakhori, A, Cordts, I, Wagner, M, Müller, AJ, Wang, ZQ

Am J Hum Genet 2020
37508007 Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

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

Antioxidants (Basel) 2023
34471290 The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway

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

Nature 2021
Participants
Participates
Catalyst Activity

4-hydroxymandelate synthase activity of HPDL:Fe2+ [mitochondrial matrix]

Orthologous Events
Cross References
RHEA
Rhea
Authored
Reviewed
Created
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