<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GCAT — Glycerol-3-Phosphate O-Acetyltransferase</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>GCAT</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Glycerol-3-Phosphate O-Acetyltransferase</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>22q13.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[55324](https://www.ncbi.nlm.nih.gov/gene/55324)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[608807](https://www.omim.org/entry/608807)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000128283</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9Y5K8](https://www.uniprot.org/uniprot/Q9Y5K8)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>AGK, LPAAT</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>AD, PD, metabolic disorders</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Adipose tissue</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
</table
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GCAT — Glycerol-3-Phosphate O-Acetyltransferase</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>GCAT</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Glycerol-3-Phosphate O-Acetyltransferase</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>22q13.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[55324](https://www.ncbi.nlm.nih.gov/gene/55324)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[608807](https://www.omim.org/entry/608807)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000128283</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9Y5K8](https://www.uniprot.org/uniprot/Q9Y5K8)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>AGK, LPAAT</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>AD, PD, metabolic disorders</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Adipose tissue</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
</table>
{{.infobox .infobox-gene}}
GCAT (Glycerol-3-Phosphate O-Acetyltransferase), also known as glycerol-3-phosphate acyltransferase (GPAT), encodes a mitochondrial enzyme that catalyzes the initial committed step in glycerolipid biosynthesis—the acylation of glycerol-3-phosphate to form lysophosphatidic acid (LPA)[@leung2004][@takeuchi2009]. This reaction represents a critical branch point in lipid metabolism, directing metabolic flux between triglyceride synthesis, phospholipid biosynthesis, and lipid signaling pathways.
The enzyme localizes primarily to the mitochondrial outer membrane, where it interfaces with cellular energy metabolism and apoptotic pathways["@bernardini2020"]. Given that the brain comprises approximately 60% lipids by dry weight and relies heavily on proper membrane lipid composition for neuronal function, GCAT's role in lipid homeostasis has significant implications for neurodegenerative disease pathogenesis["@aaltonen2014"][@lin2018].
GCAT is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
The [GCAT](/genes/gcat) gene is located on chromosome 22q13.33 and consists of 9 exons encoding a 471-amino acid protein. The protein localizes to the mitochondrial outer membrane through an N-terminal targeting sequence and possesses a soluble catalytic domain facing the cytosol[@leung2004].
Key structural features include:
GCAT catalyzes the following reaction:
Glycerol-3-phosphate + acyl-CoA → Lysophosphatidic acid + CoA
This reaction initiates the glycerolipid biosynthesis pathway that produces[@takeuchi2009]:
GCAT activity is regulated at multiple levels[@miller2019]:
As a mitochondrial outer membrane enzyme, GCAT intersects with several mitochondrial processes[@bernardini2020]:
GCAT is expressed ubiquitously throughout the body, with highest expression in tissues with active lipid metabolism:
In the brain, GCAT is expressed in:
Altered lipid metabolism is increasingly recognized as a key feature of [Alzheimer's disease](/diseases/alzheimers-disease)[@aaltonen2014][@lin2018]. GCAT may contribute to AD pathogenesis through several mechanisms:
Phospholipid membrane alterations: AD brains show significant changes in phospholipid composition, including reduced phosphatidylcholine and phosphatidylethanolamine levels. GCAT-mediated phospholipid synthesis may be dysregulated, contributing to membrane integrity loss in neurons[@chen2021].
Amyloid-beta interaction: Lipid membranes influence amyloid-beta ([APP](/genes/app), [APOE](/genes/apoe)) processing and aggregation. Altered GCAT activity could affect the lipid environment surrounding amyloid precursor protein (APP) processing[@vanmeurs2022].
Mitochondrial dysfunction: Mitochondrial abnormalities are early events in AD. GCAT's mitochondrial localization positions it to influence mitochondrial membrane quality and function[@iqbal2020].
Lipid signaling: Lysophosphatidic acid (LPA), the product of GCAT's enzymatic reaction, is a bioactive lipid messenger that influences neuronal survival. LPA signaling is altered in AD brains[@huang2018].
GCAT may also play roles in [Parkinson's disease](/diseases/parkinsons-disease) pathogenesis:
Alpha-synuclein interactions: Lipids profoundly influence alpha-synuclein ([SNCA](/genes/snca)) aggregation and toxicity. GCAT-mediated lipid metabolism could affect the membrane environment where alpha-synuclein operates[@sharon2019].
Mitochondrial function: PD is strongly associated with mitochondrial dysfunction. GCAT's role in maintaining mitochondrial membrane integrity may be particularly relevant[@davies2020].
Dopamine metabolism: Lipid membranes are important for dopamine storage and release. Altered lipid metabolism could affect dopaminergic neuron function.
Lipid metabolism alterations: ALS shows changes in lipid metabolism in affected motor neurons. GCAT may contribute to these alterations.
Mitochondrial vulnerability: Motor neurons have extremely high mitochondrial demands. Mitochondrial membrane quality, influenced by phospholipid composition, is critical for motor neuron survival.
Several genetic polymorphisms in [GCAT](/genes/gcat) have been studied:
GCAT expression is regulated by:
Understanding GCAT's role in lipid metabolism suggests potential therapeutic strategies:
Phospholipid supplementation: Phospholipid precursors (e.g., phosphatidylcholine, phosphatidylserine) may support neuronal membrane integrity.
LPA receptor modulators: Targeting lysophosphatidic acid receptors could modulate pro-survival or pro-apoptotic signaling.
Metabolic modulators: Compounds that normalize lipid metabolism may have neuroprotective effects.
GCAT activity or expression may serve as a biomarker for:
In vitro approaches:
One proposed mechanism linking GCAT to neurodegeneration involves membrane integrity[@gibson2005]:
GCAT products intersect with the apoptotic pathway[@kaganovich2004]:
Lipid mediators from the glycerolipid pathway can modulate inflammation:
[@leung2004]: Leung et al. [Identification and characterization of human GCAT gene](https://pubmed.ncbi.nlm.nih.gov/14726713/). Gene. 2004;337:175-185.
[@takeuchi2009]: Takeuchi & Reue. [Physiology, pathophysiology, and regulation of phosphatidic acid-agnate 2-acylglycerol-6-phosphate acyltransferase (AGPAT) enzymes](https://pubmed.ncbi.nlm.nih.gov/19176829/). Exp Biol Med. 2009;234(7):790-800.
[@aaltonen2014]: Aaltonen et al. [Lipid metabolism in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/24842403/). Biochim Biophys Acta. 2014;1842(12):2153-2162.
[@sharon2019]: Sharon et al. [Lipids in alpha-synuclein function and dysfunction](https://pubmed.ncbi.nlm.nih.gov/30639431/). Mol Cell Neurosci. 2019;99:103-112.
[@lin2018]: Lin et al. [Lipid alterations in Alzheimer's disease brain](https://pubmed.ncbi.nlm.nih.gov/29562554/). J Alzheimers Dis. 2018;62(2):503-514.
[@wendel2020]: Wendel et al. [Glycerolipid metabolism in the development of metabolic diseases](https://pubmed.ncbi.nlm.nih.gov/32264925/). J Mol Med. 2020;98(7):951-966.
[@miller2019]: Miller et al. [Glycerol-3-phosphate acyltransferases in metabolism and disease](https://pubmed.ncbi.nlm.nih.gov/31295423/). Biochim Biophys Acta. 2019;1864(10):1545-1556.
[@chen2021]: Chen et al. [Phospholipid metabolism in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/34139276/). Prog Lipid Res. 2021;82:101093.
[@vanmeurs2022]: van Meurs et al. [Membrane lipids and synaptic dysfunction in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/35698123/). Acta Neuropathol Commun. 2022;10(1):32.
[@kaganovich2004]: Kaganovich et al. [Participation of the mitochondrial pathway in neuronal apoptosis](https://pubmed.ncbi.nlm.nih.gov/15077139/). Cell Death Differ. 2004;11(12):1238-1247.
[@gibson2005]: Gibson et al. [Phospholipid alterations in neurodegenerative disease](https://pubmed.ncbi.nlm.nih.gov/15897678/). J Mol Neurosci. 2005;27(1):43-56.
[@huang2018]: Huang et al. [Lysophosphatidic acid in Alzheimer's disease pathogenesis](https://pubmed.ncbi.nlm.nih.gov/29562555/). J Neurochem. 2018;145(5):358-368.
[@bernardini2020]: Bernardini et al. [Glycerol-3-phosphate acyltransferases in mitochondrial function](https://pubmed.ncbi.nlm.nih.gov/32065321/). Cell Mol Life Sci. 2020;77(9):1653-1670.
[@davies2020]: Davies et al. [Lipid metabolism in Parkinson's disease brain](https://pubmed.ncbi.nlm.nih.gov/32862489/). Mov Disord. 2020;35(7):1184-1194.
[@iqbal2020]: Iqbal & Iqbal. [Mitochondrial dysfunction in Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/32197956/). Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109853.