Human liver fatty aldehyde dehydrogenase: microsomal localization, purification, and biochemical characterization

Kelson, Todd L.; McVoy, Julie R. Secor; Rizzo, William B.

doi:10.1016/s0304-4165(96)00126-2

Cited by 127 publications

(136 citation statements)

References 52 publications

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“…On the other hand, the activity of ALDH3A1 was much higher toward octanal than hexadecanal, reflecting its localization in the cytosol. These substrate preferences of ALDH3A1, ALDH3A2, and ALDH3B1 were consistent with previous studies [9,17,25]. These results indicate that ALDH3A2, ALDH3B1, ALDH3B2, and ALDH3B3 have activity toward medium-and long-chain aldehydes in common.…”

Section: Aldh3b2 and Aldh3b3 Exhibit Enzymatic Activity Toward Mediumsupporting

confidence: 92%

“…Although ALDH3A1, ALDH3A2, and ALDH3B1 have already been biochemically analyzed [9,17,25], little research has been conducted on ALDH3B2 or ALDH3B3. In the present study, we characterized both ALDH3B2 and ALDH3B3 with respect to their enzyme activity, intracellular localization, tissue distribution, and lipid modification, and compared them with the other ALDH3 subfamily members.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, Aldh3a1-knockout mice develop lens opacification and cataracts in response to UV exposure [8]. ALDH3A2 is expressed ubiquitously and exhibits activity toward saturated and unsaturated aliphatic aldehydes of C6 to C24 in length [9]. The major splicing isoform of ALDH3A2 is a type II endoplasmic reticulum (ER) membrane protein, whereas its minor isoform is localized to peroxisomes [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

Kitamura

Takagi

Naganuma

et al. 2014

Biochemical Journal

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Short title: Lipid droplet localization of ALDH3B2Summary statement: The mouse aldehyde dehydrogenases ALDH3B2 and ALDH3B3 exhibit similar substrate specificity but distinct intracellular localization (ALDH3B2, lipid droplets; ALDH3B3, plasma membrane). The C-terminal prenylation and two Trp residues are important for the lipid droplet localization of ALDH3B2.2 ABSTRACT Aldehyde dehydrogenases (ALDHs) catalyze the conversion of toxic aldehydes to non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ALDH3B3 have yet to be characterized.Here, we examined the enzyme activity, tissue distribution, and subcellular localization of ALDH3B2 and ALDH3B3. Both were found to exhibit broad substrate preferences from medium-chain to long-chain aldehydes, resembling ALDH3A2 and ALDH3B1. Although ALDH3B2 and ALDH3B3 share extremely high sequence similarity, their localizations differed, with ALDH3B2 found in lipid droplets and ALDH3B3 localized to the plasma membrane. Both ALDH3B2 and ALDH3B3 were modified by prenylation at their C-termini; this modification greatly influenced their membrane localization and enzymatic activity toward hexadecanal. We found that their C-terminal regions, particularly the two Trp residues (Trp462 and Trp469) of ALDH3B2 and the two Arg residues (Arg462 and Arg463) of ALDH3B3, were important for the determination of their specific localization. Abnormal quantity and perhaps quality of lipid droplets are implicated in several metabolic diseases. We speculate that ALDH3B2 acts to remove lipid-derived aldehydes in lipid droplets generated via oxidative stress as a quality control mechanism.

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Section: Aldh3b2 and Aldh3b3 Exhibit Enzymatic Activity Toward Mediumsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

Kitamura

Takagi

Naganuma

et al. 2014

Biochemical Journal

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“…The FALDH enzyme activity in cultured fibroblasts was measured as previously described (Kelson et al 1997). …”

Section: Faldh Enzyme Activitymentioning

confidence: 99%

Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren–Larsson syndrome

et al. 2007

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Sjögren-Larsson syndrome (SLS; MIM#270200) is an autosomal recessive neurocutaneous disease caused by mutations in the ALDH3A2 gene for fatty aldehyde dehydrogenase (FALDH), a microsomal enzyme that catalyzes the oxidation of medium-and long-chain aliphatic aldehydes to fatty acids. We studied two unrelated Italian SLS patients with ichthyosis, developmental delay, spastic diplegia and brain white matter disease. One patient was homozygous for a novel ALDH3A2 insertion mutation (c.767insA) in exon 5. The other SLS patient was a compound heterozygote for two previously reported mutations: a splice-site mutation (c.471 + 2T [ G) in intron 3 and a missense mutation (c.1094C [ T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the splice-site mutation caused skipping of exons 2 and 3. The c.1094C [ T mutation, previously associated with two ALDH3A2 haplotypes, was found on a third distinct haplotype in our patient, which indicates that it arose independently in this kindred. These results add to understanding of the genetic basis of SLS and will be useful for DNA diagnosis of this disease.

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“…Effect of Insulin on FALDH Activity in Isolated Hepatocytes-To determine whether insulin increased FALDH activity, we performed FALDH activity measurements on isolated hepatocytes after insulin stimulation (10 Ϫ7 M, 16 h) as described previously (28). As a positive control for FALDH activity, hepatocytes were infected with adenovirus expressing FALDH, and the associated FALDH activity was measured as described under "Experimental Procedures."…”

Section: Identification Of Differentially Expressed Genes By Insulinimentioning

confidence: 99%

Fatty Aldehyde Dehydrogenase

Demozay¹,

Rocchi²,

Más

et al. 2004

Journal of Biological Chemistry

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Phosphatidylinositol 3-kinase signaling regulates the expression of several genes involved in lipid and glucose homeostasis; deregulation of these genes may contribute to insulin resistance and progression toward type 2 diabetes. By employing RNA arbitrarily primed-PCR to search for novel phosphatidylinositol 3-kinase-regulated genes in response to insulin in isolated rat adipocytes, we identified fatty aldehyde dehydrogenase (FALDH), a key component of the detoxification pathway of aldehydes arising from lipid peroxidation events. Among these latter events are oxidative stresses associated with insulin resistance and diabetes. Upon insulin injection, FALDH mRNA expression increased in rat liver and white adipose tissue and was impaired in two models of insulin-resistant mice, db/db and high fat diet mice. FALDH mRNA levels were 4-fold decreased in streptozotocin-treated rats, suggesting that FALDH deregulation occurs both in hyperinsulinemic insulin-resistant state and hypoinsulinemic type 1 diabetes models. Moreover, insulin treatment increases FALDH activity in hepatocytes, and expression of FALDH was augmented during adipocyte differentiation. Considering the detoxifying role of FALDH, its deregulation in insulin-resistant and type 1 diabetic models may contribute to the lipid-derived oxidative stress. To assess the role of FALDH in the detoxification of oxidized lipid species, we evaluated the production of reactive oxygen species in normal versus FALDH-overexpressing adipocytes. Ectopic expression of FALDH significantly decreased reactive oxygen species production in cells treated by 4-hydroxynonenal, the major lipid peroxidation product, suggesting that FALDH protects against oxidative stress associated with lipid peroxidation. Taken together, our observations illustrate the importance of FALDH in insulin action and its deregulation in states associated with altered insulin signaling.Phosphatidylinositol 3-kinase (PI3K) 1 is a key component of the intracellular insulin signaling machinery. PI3K activation occurs after binding of the Src homology 2 domains of its p85 regulatory subunit to specific tyrosine-phosphorylated sites of the insulin receptor substrates (1, 2). By phosphorylating the D3 position of the inositol ring of phosphoinositides, PI3K generates the second messenger phosphatidylinositol 3,4,5-triphosphate (3-5) that participates in the recruitment and/or activation of downstream kinases such as 3-phosphoinositidedependent protein kinase-1, protein kinase B (PKB), and atypical protein kinases C and (3, 4). By activating these kinases, PI3K generates several insulin-dependent actions on metabolism such as glucose transport, glycogen synthesis, glycolysis, and lipogenesis. Moreover, PI3K acts by modulating the expression of a number of genes involved in lipid and glucose homeostasis, including phosphoenolpyruvate carboxykinase (5-7) and glucose-6-phosphatase (8), two enzymes that control key steps of gluconeogenesis in liver and the expression of which is repressed by insulin via activation of ...

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Human liver fatty aldehyde dehydrogenase: microsomal localization, purification, and biochemical characterization

Cited by 127 publications

References 52 publications

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren–Larsson syndrome

Fatty Aldehyde Dehydrogenase

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