Glycerolipid Biosynthesis in Peroxisomes via the Acyl Dihydroxyacetone Phosphate Pathway*

Hajra, Amiya K.; Bishop, James E.

doi:10.1111/j.1749-6632.1982.tb21415.x

Cited by 337 publications

(131 citation statements)

References 41 publications

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“…An important distinction between acyl-CoA: dihydroxyacetone phosphate acyltransferase, which was shown to be severely deficient in Zellweger patients (9), and the three peroxisomal enzymes we have found to be present in near normal amounts in the patients is that acyl-CoA: dihydroxyacetone phosphate transferase is a membrane-bound enzyme (4,5), whereas the other enzymes are soluble peroxisomal proteins (19).…”

Section: Discussionmentioning

confidence: 99%

Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

Wanders

Kos

Roest

et al. 1984

Biochemical and Biophysical Research Communications

203

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Section: Discussionmentioning

confidence: 99%

Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

Wanders

Kos

Roest

et al. 1984

Biochemical and Biophysical Research Communications

203

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“…An acyl-DHAP pathway has been previously described where DHAP may first be acylated followed by reduction to 1-acyl-sn-G3P. 11,12 The acyl DHAP pathway is known to have a significant role in glycerolipid synthesis in mouse liver. 12 The CPT1 and CPT2 activity were low normal in the patient's fibroblasts, but no mutations were identified in CPT1A and CPT2 genes.…”

Section: Discussionmentioning

confidence: 99%

A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia

et al. 2014

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The constellation of clinico-pathological and laboratory findings including massive hepatomegaly, steatosis, and marked hypertriglyceridemia in infancy is extremely rare. We describe a child who is presented with the above findings, and despite extensive diagnostic testing no cause could be identified. Whole exome sequencing was performed on the patient and parents' DNA. Mutations in GPD1 encoding glycerol-3-phosphate dehydrogenase that catalyzes the reversible redox reaction of dihydroxyacetone phosphate and NADH to glycerol-3-phosphate (G3P) and NAD þ were identified. The proband inherited a GPD1 deletion from the father determined using copy number analysis and a missense change p.(R229Q) from the mother. GPD1 protein was absent in the patient's liver biopsy on western blot. Low normal activity of carnitine palmitoyl transferases, CPT1 and CPT2, was present in the patient's skin fibroblasts, without mutations in genes encoding for these proteins. This is the first report of compound heterozygous mutations in GPD1 associated with a lack of GPD1 protein and reduction in CPT1 and CPT2 activity.

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“…2) shows that peroxisomes are also induced during differentiation, thus verifying previous morphological observations (4). To establish that DHAPAT in these cells is indeed peroxisomal, density gradient centrifugation was used to separate peroxisomes from other organelles (20,33,34). However, instead of using an enriched peroxisomal fraction (L fraction) the total particulate fraction was used so that the distribution of the enzymes in all extranuclear organelles can be analyzed in a single gradient.…”

Section: Differentiation-induced Increased Activity Of Lipogenic Enzymentioning

confidence: 99%

Induction of the Peroxisomal Glycerolipid-synthesizing Enzymes during Differentiation of 3T3-L1 Adipocytes

Hajra¹,

Larkins²,

Das³

et al. 2000

Journal of Biological Chemistry

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The glycerophosphate backbone for triglyceride synthesis is commonly believed to be created through the conversion of dihydroxyacetone phosphate (DHAP) by glycerophosphate dehydrogenase (GPD) to sn-glycerol 3-phosphate (GP), which is then converted by glycerophosphate acyltransferase (GPAT) to 1-acyl-GP. Consistent with this, GPD and GPAT are highly induced during differentiation of mouse 3T3-L1 preadipocytes. While the acyl dihydroxyacetone phosphate (acyl-DHAP) pathway for glycerolipid synthesis is commonly believed to be involved only in glycerol ether lipid synthesis, we report here that during conversion of 3T3-L1 preadipocytes to adipocytes, the specific activity of peroxisomal DHAP acyltransferase (DHAPAT) is increased by 9-fold in 6 days, while acyl-DHAP:NADPH reductase is induced by 5-fold. A parallel increase in the catalase (the peroxisomal marker enzyme) activity is also seen. In contrast, the specific activity of alkyl-DHAP synthase, the enzyme catalyzing the synthesis of the ether bond, is decreased by 60% during the same period. Unlike microsomal GPAT, the induced DHAPAT is found to have high activity at pH 5.5 and is resistant to inhibition by sulfhydryl agents, heat, and proteolysis. On subcellular fractionation, DHAPAT is found to be associated with microperoxisomes whereas GPAT activity is mainly present in microsomes. Northern blot analyses reveal that induction of DHAPAT can be largely explained through increases in DHAPAT mRNA. A comparison of microsomal and peroxisomal glycerolipid synthetic pathways, using Preadipocyte cell lines (1) have been widely used to study the induction of a number of enzymes and receptors and also the mechanism of differentiation at the genetic level (2, 3). The fibroblast-like mouse 3T3-L1 cells differentiate in response to high concentrations of insulin and other agents to cells that synthesize large amounts of triglycerides and are morphologically similar to adipose cells (4). A similar cell line (3T3-F442A), on transplantation in mice has been reported to develop into adipose tissue (5). During differentiation, lipogenic enzymes of the triglyceride biosynthetic pathway, as well as the ancillary enzymes needed for the formation of substrates and cofactors are induced (6). As outlined in Fig. 1, enzymes starting from the cytosolic glycerophosphate dehydrogenase (GPD), 1 catalyzing the biosynthesis of sn-glycerol 3-phosphate (GP) followed by the glycerophosphate acyltransferase (GPAT), 1-acyl-GP acyltransferase, and diacylglycerol acyltransferase (DAGAT) are highly induced during differentiation (7-9). Coleman and Bell (10) reported that due to nonspecificity of microsomal GPAT, which catalyzes the acylation of both GP and DHAP, DHAPAT activity is also induced during differentiation of these cells. All animal cells, however, have been shown to contain a specific peroxisomal DHAPAT which does not contain GPAT activity (11,12). This DHAPAT, co-localized in peroxisomes with acyl/alkyl DHAP:NADPH reductase and alkyl-DHAP synthase, is generally believed to be involve...

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Glycerolipid Biosynthesis in Peroxisomes via the Acyl Dihydroxyacetone Phosphate Pathway*

Cited by 337 publications

References 41 publications

Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia

Induction of the Peroxisomal Glycerolipid-synthesizing Enzymes during Differentiation of 3T3-L1 Adipocytes

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