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Trace amine- associated receptor 1 Sodium- dependent dopamine transporter Trace amine- associated receptor 1 Sodium- dependent dopamine transporter D(1A) dopamine receptor D(1B) dopamine receptor Synaptic vesicular amine transporter Amine oxidase [flavin- containing] A D(4) dopamine receptor Sodium- dependent dopamine transporter Synaptic vesicular amine transporter Alpha-1A adrenergic receptor Alpha-2A adrenergic receptor Trace amine- associated receptor 1 Sodium- dependent noradrenaline transporter Amine oxidase [flavin- containing] A Sodium- dependent noradrenaline transporter Beta-1 adrenergic receptor Chromaffin granule amine transporter Sodium- dependent serotonin transporter Trace amine- associated receptor 1 Sodium- dependent noradrenaline transporter Trace amine- associated receptor 1 Sodium- dependent serotonin transporter Trace amine- associated receptor 1 5- hydroxytryptamine receptor 2A Sodium- dependent serotonin transporter Amine oxidase [flavin- containing] A Sodium- dependent dopamine transporter Synaptic vesicular amine transporter Synaptic vesicular amine transporter Sodium- dependent noradrenaline transporter Synaptic vesicular amine transporter Sodium- dependent serotonin transporter Tyrosine 3-monooxygenase Aromatic-L- amino-acid decarboxylase Catechol O- methyltransferase Tyrosine 3-monooxygenase Aromatic-L- amino-acid decarboxylase Dopamine beta- hydroxylase Aromatic-L- amino-acid decarboxylase Tryptophan 5-hydroxylase 1 Dopamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Norepinephrine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Methamphetamine Serotonin Dopamine Dopamine Dopamine Methamphetamine Methamphetamine Norepinephrine Norepinephrine Norepinephrine Methamphetamine Methamphetamine Serotonin Serotonin Serotonin Methamphetamine Methamphetamine L-Tyrosine Tetrahydrobiopterin O2 L-Dopa Dihydrobiopterin H2O CO2 S- Adenosylmethionine 3- Methoxytyramine S- Adenosylhomocysteine H2O O2 Homovanillin H2O2 NH3 L-Tyrosine Sapropterin O2 L-Dopa Dihydrobiopterin H2O Dopamine CO2 Ascorbic acid O2 Dehydroascorbic acid H2O H2O O2 3,4- Dihydroxymandelaldehyde NH3 H2O2 5-Hydroxy-L- tryptophan CO2 L-Tryptophan Tetrahydrobiopterin O2 4a- Hydroxytetrahydrobiopterin H2O O2 5- Hydroxyindoleacetic acid H2O2 NH3 FAD FAD FAD Magnesium Fe2+ Pyridoxal 5'-phosphate Pyridoxal 5'-phosphate Gs signaling cascade Gs signaling cascade Gi signalling cascade Norepinephrine Alpha 1A Adrenergic Blood Vessel Relaxation Pathway Epinephrine B2-Adrenergic Bronchodilation Pathway Gs Signalling cascade Gq Signalling Cascade Gi Signalling Cascade Intestinal Serotonin pathway Gq Signalling cascade Fe2+ Pyridoxal 5'-phosphate Pyrroloquinoline quinone Copper Fe2+ Diffusion Reversal of transporter Internalization Presynaptic neuron Post synaptic neuron Synaptic vesicle Attention Impulse control Dopamine is synthesized from tyrosine in the ventral tegmental area of the brain and stored in presynaptic vesicles Methamphetamine enters the nerve terminal via the dopamine reuptake transporter or by diffusing through the membrane Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the dopamine in the vesicles causing dopamine to spew out into the cytosol Methamphetamine activates TAAR1 receptors leading to the internalization and reversal of the dopamine reuptake transporter In high doses methamphetamine inhibits monoamine oxidase, preventing metabolic degredation of dopamine, and therefore increasing the concentration of dopamine in the cytosol. Dopamine accumulates in the synapse from the reversal of the dopamine transporter as well as the inhibition of the dopamine transporter which prevents dopamine from re-entering the presynaptic neuron. The high concentration of dopamine in the synapse highly activates post-synaptic dopamine receptors which are responsible for attention, motivation, and impulse control in ADHD. D4 dopamine receptors are mainly responsible for this in ADHD. Synapse Internalization Norepinephrine is mainly produced in the locus coeruleus and then stored in presynaptic vesicles In high doses methamphetamine inhibits Amine oxidase, preventing the metabolic degredation of norepinephrine, and therefore increasing the concentration of norepinephrine in the cytosol. Methamphetamine activates Trace amine-associated receptors which causes internalization of noradrenaline reuptake transporters. This prevents the reuptake of norepinephrine from the synapse. Methamphetamine inhibits sodium-dependent dopamine transporter by being a negative modulator. This prevents the reuptake of dopamine into the neuron from the synapse. Norepinephrine accumulates in the synapse from the reversal and inhibition of noreadrenaline transporters. Methamphetamine is an agonist for Alpha 2A, 2B, and 2C adrenergic receptors, further activating them. Methamphetamine triggers the sympathetic response in the rest of the body. Increased Heart Rate Increased Breathing Rate Increased blood pressure caused by vasoconstriction Decreased appetite and digestion. Dopamine Norepinephrine Serotonin Presynaptic Neuron Cytosol Postsynaptic Neuron Methamphetamine enters the nerve terminal via the norepinephrine reuptake transporter or by diffusing through the membrane Methamphetamine inhibits sodium-dependent noradrenaline transporter by being a negative modulator. This prevents the reuptake of norepinephrine into the neuron from the synapse. Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the norepinephrine in the vesicles causing norepinephrine to spew out into the cytosol Cytosol Reversal of transport Internalization Synaptic Vesicle Synaptic Vesicle Methamphetamine activates Trace amine-associated receptors which causes internalization of serotonin reuptake transporters. This prevents the reuptake of serotonin from the synapse. Serotonin accumulates in the synapse from the reversal and inhibition of serotonin transporters. Presynaptic Neuron Intestine Smooth Muscle Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the norepinephrine in the vesicles causing serotonin to spew out into the cytosol Serotonin is produced in the raphe nuclei and then stored in presynaptic vesicles Methamphetamine enters the nerve terminal via the serotonin reuptake transporter or by diffusing through the membrane Methamphetamine inhibits sodium-dependent serotonin receptors, by being a negative modulator. This prevents the reuptake of serotonin from the synapse. Cytosol In high doses methamphetamine inhibits Amine oxidase [flavin containing] A. The inhibition of MAO A which prevents the metabolic degradation of serotonin, and therefore increases the concentration of serotonin in the cytosol. Reversal of transport Motivation Memory Attention The high concentration of Norepinephrine in the synapse highly activates post-synaptic adrenergic receptors which, in the brain, are responsible for memory retieval and formation as well as focusing attention The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B which are mainly located in the gastrointestinal tract. Here it contracts smooth muscles causing food and toxins to pass through the intestine more quickly. The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B in the brain where the exact mechanisms are unknown. It is suspected to influence mood, perception, and cognition. Mood Postsynaptic Neuron The function of Trace amine-associated receptors with norepinephrine has only been observed in mRNA expression. The function of Trace amine-associated receptors with serotonin has only been observed in mRNA expression. Perception Cognition Diffusion Diffusion
TAAR1 SLC6A3 TAAR1 SLC6A3 DRD1 DRD5 SLC18A2 MAOA DRD4 SLC6A3 SLC18A2 ADRA1A ADRA2A TAAR1 SLC6A2 MAOA SLC6A2 ADRB1 SLC18A1 SLC6A4 TAAR1 SLC6A2 TAAR1 SLC6A4 TAAR1 HTR2A SLC6A4 MAOA SLC6A3 SLC18A2 SLC18A2 SLC6A2 SLC18A2 SLC6A4 TH DDC COMT TH DDC DBH DDC TPH1 LDP Ice Ice Ice Ice Ice Norpp Ice Ice Ice Ice Ice Ice Ice Ice 5-HT LDP LDP LDP Ice Ice Norpp Norpp Norpp Ice Ice 5-HT 5-HT 5-HT Ice Ice Tyr BH4 O2 L-Dopa BH3 H2O CO2 SAMe 3-Motyr SAH H2O O2 Homovan H2O2 NH3 Tyr 6R-BH4 O2 L-Dopa BH3 H2O LDP CO2 VitC O2 DHAA H2O H2O O2 34DIHY NH3 H2O2 5-HTP CO2 Trp BH4 O2 4aHtHbp H2O O2 5HIDA H2O2 NH3 FAD FAD FAD Mg2+ Fe2+ Pyr-5'P Pyr-5'P G s c G s c Gi si c PW126707 PW125908 Gs Si c Gq Si C Gi Si C PW126797 Gq Si c Fe2+ Pyr-5'P Pqq Cu Fe2+ Diffusion Reversal of transporter Internalization Presynaptic neuron Post synaptic neuron Synaptic vesicle Attention Impulse control Dopamine is synthesized from tyrosine in the ventral tegmental area of the brain and stored in presynaptic vesicles Methamphetamine enters the nerve terminal via the dopamine reuptake transporter or by diffusing through the membrane Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the dopamine in the vesicles causing dopamine to spew out into the cytosol Methamphetamine activates TAAR1 receptors leading to the internalization and reversal of the dopamine reuptake transporter In high doses methamphetamine inhibits monoamine oxidase, preventing metabolic degredation of dopamine, and therefore increasing the concentration of dopamine in the cytosol. Dopamine accumulates in the synapse from the reversal of the dopamine transporter as well as the inhibition of the dopamine transporter which prevents dopamine from re-entering the presynaptic neuron. The high concentration of dopamine in the synapse highly activates post-synaptic dopamine receptors which are responsible for attention, motivation, and impulse control in ADHD. D4 dopamine receptors are mainly responsible for this in ADHD. Synapse Internalization Norepinephrine is mainly produced in the locus coeruleus and then stored in presynaptic vesicles In high doses methamphetamine inhibits Amine oxidase, preventing the metabolic degredation of norepinephrine, and therefore increasing the concentration of norepinephrine in the cytosol. Methamphetamine activates Trace amine-associated receptors which causes internalization of noradrenaline reuptake transporters. This prevents the reuptake of norepinephrine from the synapse. Methamphetamine inhibits sodium-dependent dopamine transporter by being a negative modulator. This prevents the reuptake of dopamine into the neuron from the synapse. Norepinephrine accumulates in the synapse from the reversal and inhibition of noreadrenaline transporters. Methamphetamine is an agonist for Alpha 2A, 2B, and 2C adrenergic receptors, further activating them. Methamphetamine triggers the sympathetic response in the rest of the body. Increased Heart Rate Increased Breathing Rate Increased blood pressure caused by vasoconstriction Decreased appetite and digestion. Dopamine Norepinephrine Serotonin Presynaptic Neuron Cytosol Postsynaptic Neuron Methamphetamine enters the nerve terminal via the norepinephrine reuptake transporter or by diffusing through the membrane Methamphetamine inhibits sodium-dependent noradrenaline transporter by being a negative modulator. This prevents the reuptake of norepinephrine into the neuron from the synapse. Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the norepinephrine in the vesicles causing norepinephrine to spew out into the cytosol Cytosol Reversal of transport Internalization Synaptic Vesicle Synaptic Vesicle Methamphetamine activates Trace amine-associated receptors which causes internalization of serotonin reuptake transporters. This prevents the reuptake of serotonin from the synapse. Serotonin accumulates in the synapse from the reversal and inhibition of serotonin transporters. Presynaptic Neuron Intestine Smooth Muscle Methamphetamine enters the synaptic vesicles through VMAT2 and inhibits VMAT2 and displaces the norepinephrine in the vesicles causing serotonin to spew out into the cytosol Serotonin is produced in the raphe nuclei and then stored in presynaptic vesicles Methamphetamine enters the nerve terminal via the serotonin reuptake transporter or by diffusing through the membrane Methamphetamine inhibits sodium-dependent serotonin receptors, by being a negative modulator. This prevents the reuptake of serotonin from the synapse. Cytosol In high doses methamphetamine inhibits Amine oxidase [flavin containing] A. The inhibition of MAO A which prevents the metabolic degradation of serotonin, and therefore increases the concentration of serotonin in the cytosol. Reversal of transport Motivation Memory Attention The high concentration of Norepinephrine in the synapse highly activates post-synaptic adrenergic receptors which, in the brain, are responsible for memory retieval and formation as well as focusing attention The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B which are mainly located in the gastrointestinal tract. Here it contracts smooth muscles causing food and toxins to pass through the intestine more quickly. The high concentration of serotonin activates 5-hydroxytryptamine receptor 2A, 3A, and 3B in the brain where the exact mechanisms are unknown. It is suspected to influence mood, perception, and cognition. Mood Postsynaptic Neuron The function of Trace amine-associated receptors with norepinephrine has only been observed in mRNA expression. The function of Trace amine-associated receptors with serotonin has only been observed in mRNA expression. Perception Cognition Diffusion Diffusion
TAAR1 SLC6A3 TAAR1 SLC6A3 DRD1 DRD5 SLC18A2 MAOA DRD4 SLC6A3 SLC18A2 ADRA1A ADRA2A TAAR1 SLC6A2 MAOA SLC6A2 ADRB1 SLC18A1 SLC6A4 TAAR1 SLC6A2 TAAR1 SLC6A4 TAAR1 HTR2A SLC6A4 MAOA SLC6A3 SLC18A2 SLC18A2 SLC6A2 SLC18A2 SLC6A4 TH DDC COMT TH DDC DBH DDC TPH1 LDP Ice Ice Ice Ice Ice Norpp Ice Ice Ice Ice Ice Ice Ice Ice 5-HT LDP LDP LDP Ice Ice Norpp Norpp Norpp Ice Ice 5-HT 5-HT 5-HT Ice Ice Tyr BH4 O2 L-Dopa BH3 H2O CO2 SAMe 3-Motyr SAH H2O O2 Homovan H2O2 NH3 Tyr 6R-BH4 O2 L-Dopa BH3 H2O LDP CO2 VitC O2 DHAA H2O H2O O2 34DIHY NH3 H2O2 5-HTP CO2 Trp BH4 O2 4aHtHbp H2O O2 5HIDA H2O2 NH3 G s c G s c Gi si c PW126707 PW125908 Gs Si c Gq Si C Gi Si C PW126797 Gq Si c