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Human lactate dehydrogenase and malate dehydrogenase possess the catalytic properties to produce aromatic α-hydroxy acid

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Abstract

Lactate dehydrogenase and malate dehydrogenase are the two main alpha-hydroxy acid dehydrogenases in the human body. We investigated the catalytic properties of human lactate dehydrogenase LDHC, LDHL6A and malate dehydrogenase MDH1 on aromatic α-keto acids phenylpyruvic acid, p-hydroxyphenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid. The optimum temperatures for LDHC, LDHL6A, and MDH1 are 37 °C, 35 °C, and 45 °C, respectively; and the optimum pH is 6.5, 6.5, and 5.5, respectively. The Km of LDHC for phenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid were 0.90 mM and 0.92 mM, respectively. LDHL6A has a high affinity for phenylpyruvic acid and 3,4-dihydroxyphenylpyruvic acid with Km of 0.77 mM and 0.80 mM, respectively; MDH1 has an extremely high affinity (Km = 0.46 mM) and catalytic efficiency (kcat/Km = 23.87 s−1·mM−1) for p-hydroxyphenylpyruvic acid. It also has a high affinity for 3,4-dihydroxyphenylpyruvic acid with a Km of 0.90 mM, but with a low affinity for phenylpyruvic acid (Km = 3.76 mM). The catalytic properties of human LDHC, LDHL6A, and MDH1 for the abovementioned aromatic α-keto acids may be one of the sources of L-phenyllactic acid, L-p-hydroxyphenyllactic acid, and L-3,4-dihydroxyphenyllactic acid in humans.

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Data availability statement

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, China

    Litong Wang & Yujie Cai

  2. Department of Pharmacology, University of Cambridge, Cambridge, CB2 1T, UK

    Tai-Ping Fan & Xiaohui Zheng

  3. Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE, Leiden, The Netherlands

    Mei Wang

  4. College of Life Sciences, Northwest University, Xi’an, 710069, Shanxi, China

    Yajun Bai & Xiaohui Zheng

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  1. Litong Wang
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Correspondence to Xiaohui Zheng or Yujie Cai.

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Wang, L., Fan, TP., Wang, M. et al. Human lactate dehydrogenase and malate dehydrogenase possess the catalytic properties to produce aromatic α-hydroxy acid. Syst Microbiol and Biomanuf 3, 627–633 (2023). https://doi.org/10.1007/s43393-022-00154-z

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