Abstract

Mitochondrial aldehyde dehydrogenase is isolated as a tetrameric enzyme but can in the presence of divalent ion cations be transformed into a more active dimericenzyme. Cytosolic enzymes are not activated. The basis for the differences in response to physiological concentrations of Mg2+ and Ca+ ions will be investigated with horse liver enzymes. Experiments to determine the in vivo state of the enzyme will be performed with rat and beef liver mitochondrial enzymes. These studies will include the use of in vivo inhibitors and in vitro hybridization of the isolated enzyme. The interrelationships between the concentration of mitochondrial aldehyde dehydrogenase and rates of aldehyde metabolism will be determined in liver slices which contain partially inactivated aldehyde dehydrogenase. An investigation of the mode of inhibition of the enzyme by various propargyl derivatives will be undertaken in order to develop potential suicide or affinity inhibitors. Lastly, the effect of alcohol on the liver isozyme pattern and molecular aggregation of aldehyde dehydrogenase will be determined in rats made dependent upon alcohol.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005812-05
Application #
3109095
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1983-04-01
Project End
1988-11-30
Budget Start
1987-04-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Earth Sciences/Resources
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Mukhopadhyay, Abhijit; Wei, Baoxian; Weiner, Henry (2013) Mitochondrial NAD dependent aldehyde dehydrogenase either from yeast or human replaces yeast cytoplasmic NADP dependent aldehyde dehydrogenase for the aerobic growth of yeast on ethanol. Biochim Biophys Acta 1830:3391-8
Weiner, Henry; Duester, Greg; Maser, Edmund et al. (2009) Enzymology and molecular biology of carbonyl metabolism. Introduction. Chem Biol Interact 178:1
Ho, Kwok Ki; Mukhopadhyay, Abhijit; Li, Yi Feng et al. (2008) A point mutation produced a class 3 aldehyde dehydrogenase with increased protective ability against the killing effect of cyclophosphamide. Biochem Pharmacol 76:690-6
Mukhopadhyay, Abhijit; Weiner, Henry (2007) Delivery of drugs and macromolecules to mitochondria. Adv Drug Deliv Rev 59:729-38
Mukhopadhyay, Abhijit; Yang, Chun-song; Wei, Baoxian et al. (2007) Precursor protein is readily degraded in mitochondrial matrix space if the leader is not processed by mitochondrial processing peptidase. J Biol Chem 282:37266-75
Brichac, Jiri; Ho, Kwok Ki; Honzatko, Ales et al. (2007) Enantioselective oxidation of trans-4-hydroxy-2-nonenal is aldehyde dehydrogenase isozyme and Mg2+ dependent. Chem Res Toxicol 20:887-95
Rodriguez-Zavala, Jose Salud; Allali-Hassani, Abdellah; Weiner, Henry (2006) Characterization of E. coli tetrameric aldehyde dehydrogenases with atypical properties compared to other aldehyde dehydrogenases. Protein Sci 15:1387-96
Ho, Kwok Ki; Hurley, Thomas D; Weiner, Henry (2006) Selective alteration of the rate-limiting step in cytosolic aldehyde dehydrogenase through random mutagenesis. Biochemistry 45:9445-53
Mukhopadhyay, Abhijit; Zullo, Steven J; Weiner, Henry (2006) Factors that might affect the allotopic replacement of a damaged mitochondrial DNA-encoded protein. Rejuvenation Res 9:182-90
Ho, Kwok Ki; Allali-Hassani, Abdellah; Hurley, Thomas D et al. (2005) Differential effects of Mg2+ ions on the individual kinetic steps of human cytosolic and mitochondrial aldehyde dehydrogenases. Biochemistry 44:8022-9

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