Human Endogenous Metabolite
Human endogenous metabolites serve critical roles in maintaining cellular and systemic homeostasis through diverse biochemical pathways[1][2]. These metabolites participate in intercellular communication, modulating signaling cascades such as kinase activation, receptor engagement, and transcriptional regulation[1][3]. For instance, β-hydroxybutyrate functions not only as an energy substrate during fasting or exercise but also as an epigenetic modifier and agonist for G-protein-coupled receptor GPR109A, influencing inflammatory and neuroprotective pathways[4]. Similarly, indoxyl 3-sulfate (I3S), a uremic metabolite, selectively activates the human aryl hydrocarbon receptor (AHR), regulating genes including CYP1A1, CYP1A2, and IL6, and contributes to pathophysiology in renal disease[5][6]. Compared with related isoforms, I3S exhibits approximately 500-fold higher potency in human AHR activation than in mouse, highlighting species-specific isoform distinctions[5]. Other metabolites, such as shikimic acid, inhibit vascular smooth muscle cell proliferation and migration through modulation of ERK1/2, AKT, and AMPK pathways, illustrating their functional relevance in cardiovascular research models[2]. Endogenous hydrogen sulfide, generated by CBS and CSE, mediates tissue-specific physiological effects in the genito-urinary system and represents a potential therapeutic target for disorders such as erectile dysfunction and preeclampsia[7]. These findings collectively support the utility of endogenous metabolites as modulators of signaling, disease biomarkers, and candidates for experimental pharmacological studies[1][8][3].
References:
- [1]. Suresh VV, et al. Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease. Biomolecules. 2025 Apr 14;15(4):580. [Content Brief]
- [2]. Schroeder JC, et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry. 2010 Jan 19;49(2):393-400. [Content Brief]
- [3]. Kot M. Aryl Hydrocarbon Receptor Establishes a Delicate Balance between the Level of the Trace Amine Tryptamine and Monoamine Oxidase Activity in the Brain and Periphery in Health and Conditions such as Neurodegenerative, et al. Aryl Hydrocarbon Receptor Establishes a Delicate Balance between the Level of the Trace Amine Tryptamine and Monoamine Oxidase Activity in the Brain and Periphery in Health and Conditions such as Neurodegenerative, Neurodevelopmental, and Psychiatric Disorders. Curr Neuropharmacol. 2025;23(11):1328-1350. [Content Brief]
- [4]. Gao J, et al. MACC: a visual interactive knowledgebase of metabolite-associated cell communications. Nucleic Acids Res. 2024 Jan 5;52(D1):D633-D639. [Content Brief]
- [5]. d'Emmanuele di Villa Bianca R, et al. The Role of the Hydrogen Sulfide Pathway in Male and Female Urogenital System in Health and Disease. Antioxid Redox Signal. 2017 Oct 1;27(10):654-668. [Content Brief]
- [6]. Kumariya S, et al. Gut microbiota-derived Metabolite, Shikimic Acid, inhibits vascular smooth muscle cell proliferation and migration. Biochem Pharmacol. 2024 Nov;229:116524. [Content Brief]
- [7]. Hwang J, et al. Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality. Life Sci. 2010 Apr 10;86(15-16):615-23. [Content Brief]
- [8]. Long MJC, et al. An Oculus to Profile and Probe Target Engagement In Vivo: How T-REX Was Born and Its Evolution into G-REX. Acc Chem Res. 2021 Feb 2;54(3):618-631. [Content Brief]
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Human Endogenous Metabolite Related Products (1396)
Related Products (1396)
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Antibodies (4)
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Norepinephrine
0 ImagesNorepinephrine (Levarterenol; L-Noradrenaline) is a potent adrenergic receptor (AR) agonist. Norepinephrine activates α1, α2, β1 receptors.
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Melatonin
0 ImagesMelatonin is a hormone made by the pineal gland that can activate melatonin receptor and inhibit PANoptosis. Melatonin plays a role in sleep and possesses important antioxidative and anti-inflammatory properties. Melatonin is a novel selective ATF-6 inhibitor and induces human hepatoma cell apoptosis through COX-2 downregulation. Melatonin attenuates palmitic acid-induced (HY-N0830) mouse granulosa cells apoptosis via endoplasmic reticulum stress.
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D-Glucose
0 ImagesD-Glucose is the naturally occurring form of glucose and the most abundant monosaccharide. D-Glucose is a critical components of the general metabolism, and serve as critical signaling molecules in relation to both cellular metabolic status and biotic or abiotic stress response.
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Liothyronine
0 ImagesSynonyms: Triiodothyronine; 3,3',5-Triiodo-L-thyronine; T3Liothyronine is an active form of thyroid hormone. Liothyronine binds to thyroid hormone receptors TRα and TRβ with Kis of 2.33 and 2.29 nM for hTRα and hTRβ, respectively. Liothyronine also binds to PVR and blocks the interaction of TIGIT/PVR.
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Spermidine
0 ImagesSpermidine maintains cell membrane stability, increases antioxidant enzymes activities, improving photosystem II (PSII), and relevant gene expression. Spermidine significantly decreases the H2O2 and O2.- contents.
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L-Kynurenine
0 ImagesL-Kynurenine is a metabolite of the amino acid L-tryptophan. L-Kynurenine is an aryl hydrocarbon receptor agonist.
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Mifepristone
0 ImagesSynonyms: RU486; RU 38486Mifepristone (RU486) is a progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist with IC50s of 0.2 nM and 2.6 nM in in vitro assay.
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L-Glutamic acid
0 ImagesL-Glutamic acid is an excitatory amino acid neurotransmitter that acts as an agonist for all subtypes of glutamate receptors (metabolic rhodophylline, NMDA, and AMPA). L-Glutamic acid has an agonist effect on the release of DA from dopaminergic nerve endings. L-Glutamic acid can be used in the study of neurological diseases. L-Glutamic acid acts at ionotropic and metabotropic glutamate receptors.
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Taurine
0 ImagesTaurine, a sulphur-containing amino acid and an organic osmolyte involved in cell volume regulation, provides a substrate for the formation of bile salts, and plays a role in the modulation of intracellular free calcium concentration. Taurine has the ability to activate autophagy in adipocytes.
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DOPE
0 ImagesSynonyms: Dioleoylphosphatidylethanolamine; 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamineDOPE (Dioleoylphosphatidylethanolamine; 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine) is an orally active inhibitor of ferroptosis with anti-inflammatory and intestinal barrier maintenance activities. DOPE regulates the expression of ACSL4, SLC7A11 and GPX4 to restore the redox system balance, thereby reducing the levels of lipid peroxides, iron ions and intestinal inflammatory factors (IL-1β and IL-6). DOPE promotes the migration and proliferation of intestinal epithelial cells and increases the level of tight junction proteins; it also destabilizes endosomal membranes, mediates the conjugation of RVG peptides with mesenchymal stem cell-derived exosomes to enhance brain targeting. DOPE can be applied to research related to neonatal necrotizing enterocolitis and Alzheimer's disease.
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Adenosine
0 ImagesAdenosine (Adenine riboside), a ubiquitous and BBB-permeable endogenous autacoid, acts through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Adenosine affects almost all aspects of cellular physiology, including neuronal activity, vascular function, platelet aggregation, and blood cell regulation.
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L-Arginine
0 ImagesL-Arginine ((S)-(+)-Arginine) is the substrate for the endothelial nitric oxide synthase (eNOS) to generate NO. L-Arginine is transported into vascular smooth muscle cells by the cationic amino acid transporter family of proteins where it is metabolized to nitric oxide (NO), polyamines, or L-proline. L-Arginine is a potent vasodilator, and can be used to induce experimental acute pancreatitis.
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Tauroursodeoxycholate
0 ImagesSynonyms: Tauroursodeoxycholic acid; TUDCA; UR 906
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Nicotinamide riboside chloride
0 ImagesNicotinamide riboside Chloride, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside Chloride is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside Chloride reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.
