ArticleThe Biochemical journal2015
Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
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- Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.Archives of biochemistry and biophysics · 2025Article
- Metabolic reprogramming in bone metastasis of human cancers.Frontiers in cell and developmental biology · 2025Review
- The new insight into the role of hydroxyproline in metabolism of cancer cells.Frontiers in cell and developmental biology · 2025Review
- Noncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs ofBiochemistry · 2024Article
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
- 4-hydroxy-2-oxoglutarate metabolism in a mouse model of Primary Hyperoxaluria Type 3.Biochemistry and biophysics reports · 2024Article
- Article
- Therapeutic targeting of HYPDH/PRODH2 with N-propargylglycine offers a Hyperoxaluria treatment opportunity.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Hydroxyproline metabolism enhances IFN-γ-induced PD-L1 expression and inhibits autophagic flux.Cell chemical biology · 2023Article
- Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression.Nature cancer · 2023Article
- Transcriptome Analysis of Redox Systems and Polyamine Metabolic Pathway in Hepatoma and Non-Tumor Hepatocyte-like Cells.Biomolecules · 2023Article
- Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?Frontiers in oncology · 2023Review
- CoQNutrients · 2022Review
- Article
- Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NADIUBMB life · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
The primary hyperoxalurias (PH), types 1-3, are disorders of glyoxylate metabolism that result in increased oxalate production and calcium oxalate stone formation. The breakdown of trans-4-hydroxy-L-proline (Hyp) from endogenous and dietary sources of collagen makes a significant contribution to the cellular glyoxylate pool. Proline dehydrogenase 2 (PRODH2), historically known as hydroxyproline oxidase, is the first step in the hydroxyproline catabolic pathway and represents a drug target to reduce the glyoxylate and oxalate burden of PH patients. This study is the first report of the expression, purification, and biochemical characterization of human PRODH2. Evaluation of a panel of N-terminal and C-terminal truncation variants indicated that residues 157-515 contain the catalytic core with one FAD molecule. The 12-fold higher k(cat)/K(m) value of 0.93 M⁻¹·s⁻¹ for Hyp over Pro demonstrates the preference for Hyp as substrate. Moreover, an anaerobic titration determined a K(d) value of 125 μM for Hyp, a value ~1600-fold lower than the K(m) value. A survey of ubiquinone analogues revealed that menadione, duroquinone, and CoQ₁ reacted more efficiently than oxygen as the terminal electron acceptor during catalysis. Taken together, these data and the slow reactivity with sodium sulfite support that PRODH2 functions as a dehydrogenase and most likely utilizes CoQ₁₀ as the terminal electron acceptor in vivo. Thus, we propose that the name of PRODH2 be changed to hydroxyproline dehydrogenase (HYPDH). Three Hyp analogues were also identified to inhibit the activity of HYPDH, representing the first steps toward the development of a novel approach to treat all forms of PH.
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