---
pmid: '20207735'
title: Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular
  defense against hyperosmotic stress.
authors:
- Brocker C
- Lassen N
- Estey T
- Pappa A
- Cantore M
- Orlova VV
- Chavakis T
- Kavanagh KL
- Oppermann U
- Vasiliou V
journal: J Biol Chem
year: '2010'
full_text_available: false
pmcid: PMC2881771
doi: 10.1074/jbc.M109.077925
pubmed_publication_types:
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
publication_type: PRIMARY_RESEARCH
---

# Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.
**Authors:** Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V
**Journal:** J Biol Chem (2010)
**DOI:** [10.1074/jbc.M109.077925](https://doi.org/10.1074/jbc.M109.077925)
**PMC:** [PMC2881771](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881771/)

## Abstract

1. J Biol Chem. 2010 Jun 11;285(24):18452-63. doi: 10.1074/jbc.M109.077925. Epub 
2010 Mar 5.

Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular 
defense against hyperosmotic stress.

Brocker C(1), Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, 
Kavanagh KL, Oppermann U, Vasiliou V.

Author information:
(1)Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, 
Colorado 80045, USA.

Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects 
against various forms of stress, such as salinity, dehydration, and osmotic 
stress. It is known that mutations in the human ALDH7A1 gene cause 
pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the 
first time that human ALDH7A1 protects against hyperosmotic stress by generating 
osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese 
hamster ovary cells attenuated osmotic stress-induced apoptosis caused by 
increased extracellular concentrations of sucrose or sodium chloride. Purified 
recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, 
including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived 
aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic 
semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate 
specificities. Tissue distribution studies in mice showed the highest expression 
of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. 
ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it 
unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse 
cDNA sequences revealed mitochondrial and cytosolic transcripts that are 
differentially expressed in a tissue-specific manner in mice. In conclusion, 
ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular 
compartments that protects against hyperosmotic stress by generating osmolytes 
and metabolizing toxic aldehydes.

DOI: 10.1074/jbc.M109.077925
PMCID: PMC2881771
PMID: 20207735 [Indexed for MEDLINE]