SLC7A1 Gene

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gene958 wordssynced 2026-04-02

SLC7A1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC7A1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC7A1</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Solute Carrier Family 7 Member 1</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>CAT1, CAT-1, ATRC1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6541</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000147614</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P30825</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>~4.2 kb</td>
</tr>
<tr>
<td class="label">Exon Count</td>
<td>14 exons</td>
</tr>
<tr>
<td class="label">Amino Acid</td>
<td>Affinity (Km)</td>
</tr>
<tr>
<td class="label">L-Arginine</td>
<td>~100 μM</td>
</tr>
<tr>
<td class="label">L-Lysine</td>
<td>~150 μM</td>
</tr>
<tr>
<td class="label">L-Ornithine</td>
<td>~200 μM</td>
</tr>
<tr>
<td class="label">L-Histidine</td>
<td>~500 μM</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Evidence</td>
</tr>
<tr>
<td class="label">L-arginine supplementation</td>
<td>Cognitive improvement in AD models</td>
</tr>
<tr>
<td class="label">L-ornithine supplementation</td>
<td>Enhanced polyamine synthesis</td>
</tr>
<tr>
<td class="label">Ar

...

SLC7A1 Gene

Overview

Mermaid diagram (expand to render)

SLC7A1 (Solute Carrier Family 7 Member 1), also known as CAT-1 (Cationic Amino Acid Transporter 1), is a high-affinity transmembrane transporter that mediates cellular uptake of cationic amino acids, particularly L-arginine, L-lysine, and L-ornithine["@mann2003"]. This transporter plays critical roles in nitric oxide synthesis, polyamine production, and neurotransmitter regulation in the brain, making it highly relevant to neurodegenerative disease research.

As the major cationic amino acid transporter in the central nervous system, SLC7A1 is essential for maintaining arginine availability for multiple critical pathways including nitric oxide (NO) synthesis, creatine biosynthesis, and neurotransmitter metabolism. Dysregulation of SLC7A1 has been implicated in both Alzheimer's and Parkinson's diseases.

Gene Structure and Expression

Genomic Organization

Protein Structure

SLC7A1 encodes a 629-amino acid membrane protein with 14 transmembrane domains. The protein features:

N-terminal extracellular domain: Contains glycosylation sites
Transmembrane helices: 14 membrane-spanning regions
C-terminal intracellular domain: Contains regulatory motifs
Substrate binding site: Central channel for cation transport

The transporter requires heterodimerization with SLC3A1 (4F2hc) for proper trafficking to the plasma membrane. This heterodimer complex is essential for functional expression.

Normal Biological Functions

Amino Acid Transport

SLC7A1 transports cationic amino acids with distinct kinetics[@closs1996]:

The transporter operates as a facilitated diffusion system, allowing bidirectional transport depending on concentration gradients. Under physiological conditions, net uptake of arginine occurs.

Nitric Oxide Synthesis

Arginine is the sole substrate for nitric oxide synthase (NOS), making SLC7A1 critical for NO production:

Endothelial NOS (eNOS): Vascular tone regulation
Neuronal NOS (nNOS): Neurotransmission
Inducible NOS (iNOS): Immune response

NO dysregulation contributes to neurovascular dysfunction in neurodegenerative diseases[@van2020].

Polyamine Synthesis

Arginine serves as the precursor for polyamine biosynthesis:

Ornithine → Putrescine → Spermidine → Spermine
Critical for neuronal survival
Involved in synaptic plasticity
Protects against oxidative stress

Neurotransmitter Metabolism

SLC7A1 indirectly affects neurotransmitter metabolism:

Arginine is a precursor for agmatine
Involved in creatine biosynthesis
Supports dopamine metabolism

Expression in Brain

Regional Distribution

SLC7A1 shows region-specific expression in the brain[@kakigi2014]:

Highest expression: Cerebral cortex, hippocampus
Moderate expression: Cerebellum, basal ganglia
Lower expression: Thalamus, hypothalamus

Cell Type Expression

Neurons: High expression in pyramidal neurons
Endothelial cells: Blood-brain barrier
Astrocytes: Perivascular astrocyte end-feet
Microglia: Moderate expression

Developmental Expression

SLC7A1 expression changes during development:

Low expression in embryonic brain
Peaks during postnatal development
Maintained in adult brain
Decreases with age

Role in Neurodegeneration

Alzheimer's Disease

Multiple studies link SLC7A1 to AD pathogenesis:

L-Arginine Transport Deficiency

Reduced SLC7A1 expression in AD brain[@gulys2015]
Impaired arginine uptake in AD neurons
Decreased NO production
Reduced polyamine levels

Neurovascular Dysfunction

SLC7A1-mediated arginine transport supports neurovascular coupling[@van2020]:

Endothelial arginine uptake for NO synthesis
Blood flow regulation
Blood-brain barrier maintenance
Cerebral perfusion

Therapeutic Implications

L-arginine supplementation has shown promise in AD models[@huang2020]:

Improved cognitive function
Enhanced synaptic plasticity
Reduced oxidative stress
Neuroprotective effects

Parkinson's Disease

SLC7A1 alterations in PD models have been reported[@li2003]:

Altered cationic amino acid transport
Reduced arginine availability
Impaired NO synthesis
Dopaminergic neuron vulnerability

Mechanisms

Mitochondrial dysfunction linked to arginine deficiency
NO signaling impairment
Polyamine depletion
Oxidative stress vulnerability

Other Neurodegenerative Conditions

Stroke: Reduced SLC7A1 in ischemic tissue
Amyotrophic lateral sclerosis: Motor neuron vulnerability
Huntington's disease: Polyamine pathway alterations

Therapeutic Targeting

Arginine Supplementation

Transport Modulation

Small molecule SLC7A1 activators
Heterodimer stabilization
Regulatory pathway targeting

Biomarkers

Arginine levels in CSF
NO metabolites
Polyamine levels

Animal Models

Knockout Mice

SLC7A1 knockout mice display:

Embryonic lethality (complete knockout)
Urea cycle abnormalities
Growth retardation
Neurological deficits

Conditional Knockout

Brain-specific knockout shows:

Impaired NO synthesis
Behavioral abnormalities
Synaptic dysfunction
Learning deficits

Transgenic Overexpression

Motor neuron-specific overexpression:

Protection in disease models
Enhanced amino acid uptake
Improved function

Clinical Considerations

Biomarkers

Plasma arginine levels
NO metabolites in CSF
Polyamine measurements

Therapeutic Approaches

Dietary arginine supplementation
Polyamine administration
NO donors (caution needed)

Drug Interactions

Arginine competes with lysine for transport
NOS inhibitors affect downstream pathways
Polyamine synthesis intermediates

Key Publications

[Closs et al., Membrane topology of CAT-1 (1996)](https://pubmed.ncbi.nlm.nih.gov/8825383/)

[Mann et al., Structure and function of CATs (2003)](https://pubmed.ncbi.nlm.nih.gov/12517427/)

[Schneider et al., hCAT-1 in endothelial cells (2001)](https://pubmed.ncbi.nlm.nih.gov/11561020/)

[Shin et al., Neuronal expression of CAT-1 (2006)](https://pubmed.ncbi.nlm.nih.gov/16739021/)

[Huang et al., L-arginine and cognitive function (2020)](https://pubmed.ncbi.nlm.nih.gov/32920468/)

[Gulyás et al., PET imaging of hCAT (2015)](https://pubmed.ncbi.nlm.nih.gov/25669902/)

[Li et al., Cationic amino acid transporters in PD (2003)](https://pubmed.ncbi.nlm.nih.gov/14552890/)

External Links

[NCBI Gene: SLC7A1](https://www.ncbi.nlm.nih.gov/gene/6541)
[UniProt: P30825](https://www.uniprot.org/uniprot/P30825)
[GeneCards: SLC7A1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC7A1)
[OMIM: 104615](https://www.omim.org/entry/104615)

Pathway Diagram

The following diagram shows the key molecular relationships involving SLC7A1 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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SLC7A1 Gene

SLC7A1 Gene

SLC7A1 Gene

Overview

Gene Structure and Expression

Genomic Organization

Protein Structure

Normal Biological Functions

Amino Acid Transport

Nitric Oxide Synthesis

Polyamine Synthesis

Neurotransmitter Metabolism

Expression in Brain

Regional Distribution

Cell Type Expression

Developmental Expression

Role in Neurodegeneration

Alzheimer's Disease

L-Arginine Transport Deficiency

Neurovascular Dysfunction

Therapeutic Implications

Parkinson's Disease

Mechanisms

Other Neurodegenerative Conditions

Therapeutic Targeting

Arginine Supplementation

Transport Modulation

Biomarkers

Animal Models

Knockout Mice

Conditional Knockout

Transgenic Overexpression

Clinical Considerations

Biomarkers

Therapeutic Approaches

Drug Interactions

Key Publications

External Links

See Also

Pathway Diagram