Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of L-leucine import across plasma membrane. [GO_REF:0000058, GOC:TermGenie, PMID:10467003]
The biological process of positive regulation of L-leucine import across the plasma membrane involves a complex interplay of transporters, signaling pathways, and cellular mechanisms.
**1. Transporter Proteins:**
- **SLC7A5 (LAT1):** This is a primary transporter responsible for the uptake of branched-chain amino acids (BCAAs), including L-leucine, across the plasma membrane. LAT1 requires the presence of a co-transporter, SLC3A2 (4F2hc), for its proper function.
- **SLC38A2 (SNAT2):** This transporter is responsible for the uptake of L-leucine via system A transport. This system is sodium-dependent and is primarily responsible for the uptake of neutral amino acids, including L-leucine, from the blood into cells.
**2. Signaling Pathways:**
- **mTORC1 Pathway:** The mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and metabolism. It plays a critical role in regulating the expression and activity of both LAT1 and SNAT2.
- When amino acid levels are high, mTORC1 is activated, leading to increased transcription of genes involved in amino acid transport, including LAT1 and SNAT2.
- This increased expression enhances L-leucine uptake into cells.
- **Insulin Signaling Pathway:** Insulin, a key regulator of glucose metabolism, also plays a role in L-leucine transport.
- Insulin stimulation can activate mTORC1, leading to increased L-leucine uptake through the activation of LAT1 and SNAT2.
- **Amino Acid Sensing Mechanisms:**
- Cells possess mechanisms to sense intracellular amino acid concentrations. When L-leucine levels are low, this triggers a signaling cascade that increases the activity of the transporters.
- This mechanism ensures that cells can maintain sufficient levels of L-leucine for protein synthesis and other cellular functions.
**3. Cellular Processes:**
- **Protein Synthesis:** L-leucine is an essential amino acid required for protein synthesis. Increased L-leucine import is crucial for supporting protein synthesis during cell growth and development.
- **Energy Metabolism:** L-leucine can be utilized as a source of energy in some tissues. Increased L-leucine uptake can contribute to energy production when other energy sources are limited.
- **Cell Signaling:** L-leucine is involved in various cell signaling pathways, including mTORC1, that regulate cellular processes such as growth, proliferation, and metabolism.
**4. Regulation of L-leucine Import:**
- **Transcriptional regulation:** Transcription factors, like the transcription factor CHOP (CCAAT/enhancer-binding protein homologous protein) and others, can regulate the transcription of LAT1 and SNAT2 genes, influencing the overall availability of these transporters.
- **Post-translational modifications:** Phosphorylation of LAT1 and SNAT2 can affect their activity. These modifications can be triggered by signaling pathways like mTORC1, insulin signaling, and others.
- **Cellular localization:** The distribution of LAT1 and SNAT2 within the plasma membrane can be influenced by various factors, impacting the efficiency of L-leucine import.
The precise mechanisms and relative contributions of these different aspects may vary depending on the specific cell type and physiological context. However, the coordinated action of these transporters, signaling pathways, and cellular processes ensures efficient L-leucine import across the plasma membrane, contributing to essential cellular functions.'"
Protein | Definition | Taxonomy |
---|---|---|
Large neutral amino acids transporter small subunit 1 | A large neutral amino acids transporter small subunit 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q01650] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
glycine | alpha-amino acid; amino acid zwitterion; proteinogenic amino acid; serine family amino acid | EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor; fundamental metabolite; hepatoprotective agent; micronutrient; neurotransmitter; NMDA receptor agonist; nutraceutical | |
levodopa | L-dopa : An optically active form of dopa having L-configuration. Used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease Levodopa: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. | amino acid zwitterion; dopa; L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | allelochemical; antidyskinesia agent; antiparkinson drug; dopaminergic agent; hapten; human metabolite; mouse metabolite; neurotoxin; plant growth retardant; plant metabolite; prodrug |
tyrosine | tyrosine : An alpha-amino acid that is phenylalanine bearing a hydroxy substituent at position 4 on the phenyl ring. Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin. | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; proteinogenic amino acid; tyrosine | EC 1.3.1.43 (arogenate dehydrogenase) inhibitor; fundamental metabolite; micronutrient; nutraceutical |
leucine | leucine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isobutyl group. Leucine: An essential branched-chain amino acid important for hemoglobin formation. | amino acid zwitterion; L-alpha-amino acid; leucine; proteinogenic amino acid; pyruvate family amino acid | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite |
methionine | methionine : A sulfur-containing amino acid that is butyric acid bearing an amino substituent at position 2 and a methylthio substituent at position 4. Methionine: A sulfur-containing essential L-amino acid that is important in many body functions. | aspartate family amino acid; L-alpha-amino acid; methionine; methionine zwitterion; proteinogenic amino acid | antidote to paracetamol poisoning; human metabolite; micronutrient; mouse metabolite; nutraceutical |
phenylalanine | L-phenylalanine : The L-enantiomer of phenylalanine. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group. Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE. | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid | algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
histidine | histidine : An alpha-amino acid that is propanoic acid bearing an amino substituent at position 2 and a 1H-imidazol-4-yl group at position 3. Histidine: An essential amino acid that is required for the production of HISTAMINE. L-histidine : The L-enantiomer of the amino acid histidine. | amino acid zwitterion; histidine; L-alpha-amino acid; polar amino acid zwitterion; proteinogenic amino acid | algal metabolite; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; Saccharomyces cerevisiae metabolite |
valine | L-valine : The L-enantiomer of valine. valine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isopropyl group. Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. | L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid; pyruvate family amino acid; valine | algal metabolite; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; Saccharomyces cerevisiae metabolite |
tryptophan | tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid; tryptophan; tryptophan zwitterion | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
isoleucine | isoleucine : A 2-amino-3-methylpentanoic acid having either (2R,3R)- or (2S,3S)-configuration. Isoleucine: An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. L-isoleucine : The L-enantiomer of isoleucine. | aspartate family amino acid; isoleucine; L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite |
D-tryptophan | D-alpha-amino acid; tryptophan; tryptophan zwitterion | bacterial metabolite | |
copper histidine | D-alpha-amino acid; histidine; polar amino acid zwitterion | Saccharomyces cerevisiae metabolite | |
D-tyrosine | D-alpha-amino acid; D-alpha-amino acid zwitterion; tyrosine | Escherichia coli metabolite | |
D-valine | D-valine : The D-enantiomer of valine. | D-alpha-amino acid; D-alpha-amino acid zwitterion; valine | |
phenylalanine | D-alpha-amino acid; D-alpha-amino acid zwitterion; phenylalanine | ||
1-methylhistidine | 1-methylhistidine : A methylhistidine in which the methyl group is located at N-1. 1-methylhistidine: found in muscle proteins; RN given refers to (L)-isomer N(tele)-methyl-L-histidine : A L-histidine derivative in which the methyl group is at N(tele)-position. | L-histidine derivative; non-proteinogenic L-alpha-amino acid; zwitterion | human metabolite |
2-aminobicyclo(2,2,1)heptane-2-carboxylic acid | 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid: amino acid analog; releases insulin; RN given refers to unlabeled cpd without isomeric designation | monoterpenoid | |
D-leucine | D-alpha-amino acid; D-alpha-amino acid zwitterion; leucine | bacterial metabolite; Saccharomyces cerevisiae metabolite | |
3-tyrosine | 3-tyrosine: RN given refers to cpd with unspecified isomeric designation L-m-tyrosine : A hydroxyphenylalanine that is L-phenylalanine with a substituent hydroxy group at position 3. | hydroxyphenylalanine; L-alpha-amino acid zwitterion; L-phenylalanine derivative; non-proteinogenic L-alpha-amino acid; phenols | plant metabolite |