Disease relevance of ALDH4A1

• The conceptual translation of human P5CDh has 89% sequence identity with the published human P5CDh peptide sequences and 42 and 26% identity with Saccharomyces cerevisiae and Escherichia coli P5CDhs, respectively, as well as homology to several other aldehyde dehydrogenases [1].
• We have confirmed the P5CDh activity of the Thermus thermophilus protein TT0033 (TtP5CDh), and determined the crystal structure of the enzyme in the ligand-free form at 1.4 A resolution [2].
• Our research could be a further understanding of the biological significance of this P5CDh-ANF enzyme, with important potential applications in the treatment of HPII and liver diseases and in liver transplantation [3].

High impact information on ALDH4A1

• To test the functional consequences of three of these, we expressed them in a P5CDh-deficient strain of Saccharomyces cerevisiae . In contrast to wild-type human P5CDh, yeast expressing S352L and G521fs(+1) failed to grow on proline and had no detectable P5CDh activity [4].
• As an initial step in understanding the biochemistry of human P5CDh and molecular basis of HPII, we utilized published peptide sequence data and degenerate primer polymerase chain reaction to clone two full-length human P5CDh cDNAs, differing in length by 1 kilobase pair (kb) [1].
• The P5CDh structural gene appears to be single copy with a size of about 20 kb localized to chromosome 1 [1].
• In this paper we report an 800-fold purification P5C dehydrogenase from rat liver mitochondria to yield an essentially homogenous protein [5].
• The fis1 gene has 73% homology with an Arabidopsis gene which encodes delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH) which is a part of the proline degradation pathway [6].

Biological context of ALDH4A1

• These results suggest that p53 might play a protective role against cell damage induced by generation of intracellular ROS, through transcriptional activation of ALDH4 [7].
• Inhibition of ALDH4 expression by antisense oligonucleotides was able to enhance cell death induced by infection with Ad-p53 [7].
• Expression of ALDH4 mRNA was induced in HCT116 cells in response to DNA damage caused by adriamycin treatment, in a p53-dependent manner [7].
• The activity of P5C metabolizing enzymes: OAT, P5CR, PO, and P5CD, in the camel tick Hyalomma dromedarii has been followed throughout embryogenesis [8].

Associations of ALDH4A1 with chemical compounds

• Human liver high Km aldehyde dehydrogenase (ALDH4): properties and structural relationship to the glutamic gamma-semialdehyde dehydrogenase [9].
• Cr(III) at 32 mg/L altered the expression of five genes, including GSTtau, GSTalpha, and ALDH4 [10].

Other interactions of ALDH4A1

• The second origin was activated in the second hour of S and was mapped to a CpG island near the promoter of the aldehyde dehydrogenase 4A1 (ALDH4A1) gene [11].

Analytical, diagnostic and therapeutic context of ALDH4A1

• Both P5CDh cDNA clones detect a single 3.2-kb transcript on Northern blots of multiple human tissues, indicating the long cDNA containing the 3'-untranslated intron represents the predominant transcript [1].
• H1299 cells transformed to over-express ALDH4 showed significantly lower intracellular reactive oxygen species (ROS) levels than parental or control cells after treatment with hydrogen peroxide or UV [7].

References