{"id":2500,"date":"2021-02-05T06:37:02","date_gmt":"2021-02-05T06:37:02","guid":{"rendered":"https:\/\/tochtroplab.org\/?page_id=2500"},"modified":"2021-02-05T06:53:07","modified_gmt":"2021-02-05T06:53:07","slug":"metabolism-and-signaling-of-4-hydroxy-acids-and-aldehydes","status":"publish","type":"page","link":"https:\/\/tochtroplab.org\/?page_id=2500","title":{"rendered":"Metabolism and signaling of 4-hydroxy acids and aldehydes."},"content":{"rendered":"
<\/p>\n
Over the past eight years we, along with collaborators Henri Brunengraber (CWRU) and Guofang Zhang (Duke), have published 16 manuscripts detailing the metabolism of 4-hydroxy acids and aldehydes. Likely the <\/span>most important finding from our work was published in two manuscripts (JBC 2009; JACS 2010) where we <\/span>showed that the dogmatic lipid peroxidation product, 4-hydroxynonenal (4-HNE) could be metabolized through <\/span>a novel pathway that involves the recycling of the carbon framework to acetyl-CoA, propionyl-CoA, and <\/span>formate. Prior to this work, it was generally thought that the fates of 4-HNE consisted of either glutathionylation <\/span>and excretion, or adduction of proteins and DNA. In a series of five subsequent papers, we were able to prove <\/span>that the catabolic pathways we discovered are the primary route of disposal of 4-HNE under normal <\/span>physiologic conditions. Further, we were able to discover that it is only under conditions of impaired \u03b2- <\/span>oxidation that 4-HNE glutathionylation or protein adduction becomes relevant. Going forward our goal is to <\/span>prove the relevance of this hypothesis in various disease states, and argue for a more fundamental role for <\/span>LPO in normal physiology, and more clearly define how these \u2018normal\u2019 processes are disrupted during disease.<\/span><\/div>\n
a. Wilson KA, Han Y, Zhang M, Hess JP, Chapman KA, Cline GW, Tochtrop GP, Brunengraber H, Zhang GF. Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to<\/span><\/div>\n
    disorders of propionyl-CoA metabolism. Am J Physiol Endocrinol Metab. 2017;313, E413-E428. PMID:28634175<\/span><\/div>\n

<\/span><\/div>\n
b. Sadhukhan S, Han Y, Jin Z, Tochtrop GP*, Zhang GF*. Glutathionylated 4-hydroxy-2-(E)-alkenal enantiomers in rat organs and their contributions toward the disposal of 4-hydroxy-2-(E)-nonenal in rat<\/span><\/div>\n
     liver. Free Radical Biol Med. 2014;70:78-85. PMID: 4040968.<\/div>\n
<\/div>\n
c. Sadhukhan S, Zhang GF, Tochtrop GP*. Modular isotopomer synthesis of gamma-hydroxybutyric acid for a quantitative analysis of metabolic fates. ACS Chem. Biol. 2014;9:1706-11. PMID: 4136706.<\/span><\/div>\n
<\/div>\n
d. Zhang GF, Kombu RS, Kasumov T, Han Y, Sadhukhan S, Zhang J, Sayre LM, Ray D, Gibson KM, Anderson VA, Tochtrop GP, Brunengraber H. Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-<\/span>hydroxy        4-phosphoacyl-CoAs. J Biol Chem. 2009;284:33521-34. PMID: 2785196.<\/span><\/div>\n

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