Quantitative metabolomics services for biomarker discovery and validation.
Specializing in ready to use metabolomics kits.
Your source for quantitative metabolomics technologies and bioinformatics.
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Small Molecule Pathway Database.

Pathways

Showing 1 - 10 of 27877 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP00055

Pw000001 View Pathway
metabolic

Alanine Metabolism

Homo sapiens
Alanine is most commonly produced by the reductive amination of pyruvate via alanine transaminase. This reversible reaction involves the interconversion of alanine and pyruvate, coupled to the interconversion of alpha-ketoglutarate (2-oxoglutarate) and glutamate. Because transamination reactions are readily reversible and pyruvate is widespread, alanine can be easily formed in most tissues. Another route to the production of alanine is through the enzyme called alanine-glyoxylate transaminase. This reaction involves the interconversion of alanine and pyruvate, coupled to the interconversion of glyoxylate and glycine. Once synthesized, alanine can be coupled to alanyl tRNA via alanyl-tRNA synthetase and used by the body in protein synthesis. Alanine constitutes about 8% of human proteins. Under fasting conditions, alanine, derived from protein breakdown, can be converted to pyruvate and used to synthesize glucose via gluconeogenesis in the liver. Alternately, alanine, after conversion to pyruvate, can be fully oxidized via the TCA cycle in other tissues.

SMP00018

Pw000006 View Pathway
metabolic

Alpha Linolenic Acid and Linoleic Acid Metabolism

Homo sapiens
Linoleic acid is a member of essential fatty acids called omega-6 fatty acids. It is an essential dietary requirement for all mammals. The other group of essential fatty acids is the omega-3 fatty acids (i.e. alpha-linolenic acid). The first step in the metabolism of linoleic acid (LA) is performed by Δ-6-desaturase, which converts LA into gamma-linolenic acid (GLA). GLA is converted to dihomo-gamma-linolenic acid (DGLA), which in turn is converted to arachidonic acid (AA). One of the possible fates of AA is to be transformed into a group of metabolites called eicosanoids. There are three types of eicosanoids are prostaglandins, thromboxanes, and leukotrienes. α-Linolenic acid (ALA), is an essential 18:3n or omega-3 fatty acid. It is considered essential because it cannot be produced entirely within the body and must be acquired through diet. Once acquired, α-Linolenic acid can be “regenerated” endogenously by the cleavage of phospholipids into their constituent fatty acids by phospholipase A2. The resulting fatty acid can then be converted to stearidonic acid through the action of fatty acid desaturase 2. α-Linolenic acid is primarily used by the body in the synthesis of Eicosapentaenoic acid (EPA; 20:5, n−3) and docosahexaenoic acid (DHA; 22:6, n−3), two fatty acids that play a vital role in many metabolic and cell signaling processes. These fatty acids are synthesized via fatty acid desaturase 2, fatty acid desaturase 1 and several elongase enzymes (Q9GZR5) in the liver. α-Linolenic acid is also in the regulation of lipid metabolism by activation of the peroxisome proliferators-activated receptor alpha (PPARa).

SMP00045

Pw000008 View Pathway
metabolic

Amino Sugar Metabolism

Homo sapiens
This pathway describes the biosynthesis and degradation of amino sugars, glycosaminoglycans or mucopolysaccharides. Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. Members of the glycosaminoglycan family vary in the type of hexosamine, hexose or hexuronic acid unit they contain (e.g. glucuronic acid, iduronic acid, galactose, galactosamine, glucosamine). In this pathway the fates of three types of amino sugars (neuraminate, mannosamine and glucosamines) are depicted. The central hub metabolite to this pathway is UDP-N-acetyl-D-glucosamine. This molecule can either serve as a precursor to polymeric mucopolysaccharides, a precursor to other types of amino sugars, or a precursor to fructose 6-phosphate, which can be used in fructose/mannose metabolism.

SMP00009

Pw000009 View Pathway
metabolic

Ammonia Recycling

Homo sapiens
This pathway describes some of the routes by which ammonia is generated or re-used as part of nitrogen metabolism. Seven amino acids play a key role in this process: glutamate, glutamine, glycine, serine, histidine, aspartate and asparagines. Glutamate and glutamine are the two important amino acids in recycling ammonia in our body instead of excreting it as waste in form of urea. Glutamine is synthesized from glutamate by incorporation of an NH3 into the carboxyl group forming an amide. This step requires ATP and is catalyzed by glutamine synthetase. The coupling of glutamine synthesis with ATP hydrolysis renders the reaction irreversible. The back reaction - the regeneration of glutamate from glutamine - is catalyzed by glutaminase, which deaminates glutamine via a hydrolysis reaction. Transamination reactions also play an important role in nitrogen/ammonia metabolism. In particular, the interplay of two additional enzymes: glutamate transaminase and glutamate dehydrogenase is essential in the control of nitrogen balance in the body. Beyond the role of glutamate and glutamine in nitrogen metabolism, the action of asparaginase on asparagine (to generate aspartate and ammonia) is another route to generate and recycle ammonia. Ammonia is also generated or recycled through the action of the glycine cleavage system (ammoniamethyltransferase) on glycine. Furthermore, ammonia can be recycled through the action of histidine ammonia lyase which acts on histidine to generate urocanate and ammonia. Another amino acid, serine, can also play a part in ammonia recycling through the action of serine dehydratase. This enzyme cleaves serine into pyruvate and ammonia.

SMP00068

Pw000045 View Pathway
metabolic

Androgen and Estrogen Metabolism

Homo sapiens
This pathway describes the inactivation and catabolism of male (androgen) and female (estrogen) hormones. Many steroid hormones are transformed by sulfatases, dehydrogenases and glucuronide transferases to enhance their solubility and to facilitate their elimination. Inactivation refers to the metabolic conversion of a biologically active compound into an inactive one. Peripheral inactivation (e.g. by liver enzymes) is required to ensure steady-state levels of plasma androgens and estrogens. Specifically, if an androgen or estrogen is to act as a " chemical signal ", its half-life in the circulation must be limited, so that any change in secretion rate is immediately reflected by a change in its plasma concentration. But hormone inactivation can also occur in target tissues, notably after the hormone has triggered the relevant biological effects in order to ensure termination of hormone action. The main site of peripheral androgen/estrogen inactivation and catabolism is the liver, but some catabolic activity also occurs in the kidneys. Inactive androgens and estrogens are mainly eliminated as urinary (mostly conjugated) metabolites. This elimination requires conversion to hydrophilic compounds in order to ensure their solubility in biological fluids at rather high concentrations. Depending on the structure of the starting steroid there may be: 1) Reduction of a double bond at C-4 and reduction of an oxo(keto) group at C-3 to a secondary alcoholic group; 2) Reduction of an oxo group at C-20 to a secondary alcoholic group; 3) Oxidation of a 17ß-hydroxyl group; 4) Further hydroxylations at various positions of the steroid nucleus (e.g. 7-hydroxylation of 5a-reduced androgens) or 5) Conjugation (sulphate and/or glucuronide derivatives).

SMP30406

Pw031290 View Pathway
metabolic

Androstenedione Metabolism

Homo sapiens
Androstenedione is an endogenous weak androgen steroid hormone that is a precursor of testosterone and other androgens, as well as of estrogens like estrone (Wikipedia). Its metabolism occurs primarily in the endoplasmic reticulum (membrane-associated enzymes are coloured dark green in the image). Conversion of androstenedione to testosterone requires the enzyme testosterone 17-beta-dehydrogenase 3. Conversion of androstenedione to estrone involves three successive reactions catalyzed by the enzyme aromatase (cytochrome P450 19A1). Androstenedione can also be converted into etiocholanolone glucuronide, androsterone glucuronide, and adrenosterone. The three-reaction subpathway to synthesize etiocholanolone glucuronide begins with the enzyme 3-oxo-5-beta-steroid 4-dehydrogenase catalyzing the conversion of androstenedione to etiocholanedione. This is followed by the conversion of etiocholanedione to etiocholanolone which is catalyzed by aldo-keto reductase family 1 member C4. Lastly, the large membrane-associated multimer UDP-glucuronosyltransferase 1-1 catalyzes the conversion of etiocholanolone to etiocholanolone glucuronide. The three-reaction subpathway to synthesize androsterone glucuronide begins with the conversion of androstenedione to androstanedione via 3-oxo-5-alpha-steroid 4-dehydrogenase 1. Anstrostanedione is then converted into androsterone via aldo-keto reductase family 1 member C4. The last reaction to form androsterone glucuronide is catalyzed by the large multimer UDP-glucuronosyltransferase 1-1. The two-reaction subpathway to synthesize adrenosterone begins in the mitochondrial inner membrane where androstenedione is first converted into 11beta-hydroxyandrost-4-ene-3,17-dione by the enzyme cytochrome P450 11B1. Following transport to the endoplasmic reticulum, 11beta-hydroxyandrost-4-ene-3,17-dione is converted into adrenosterone via corticosteroid 11-beta-dehydrogenase isozyme 1.

SMP00075

Pw000044 View Pathway
metabolic

Arachidonic Acid Metabolism

Homo sapiens
This pathway describes the production and subsequent metabolism of arachidonic acid, an omega-6 fatty acid. In resting cells arachidonic acid is present in the phospholipids (especially phosphatidylethanolamine and phosphatidylcholine) of membranes of the body’s cells, and is particularly abundant in the brain. Typically a receptor-dependent event, requiring a transducing G protein, initiates phospholipid hydrolysis and releases the fatty acid into the intracellular medium. Three enzymes mediate this deacylation reaction including phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Once released, free arachidonate has three possible fates: 1) reincorporation into phospholipids, 2) diffusion outside the cell, and 3) metabolism. Arachidonate metabolism is carried out by three distinct enzyme classes: cyclooxygenases, lipoxygenases, and cytochrome P450’s. Specifically, the enzymes cyclooxygenase and peroxidase lead to the synthesis of prostaglandin H2, which in turn is used to produce the prostaglandins, prostacyclin, and thromboxanes. The enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. Some arachidonic acid is converted into midchain HETEs, omega-chain HETEs, dihydroxyeicosatrienoic acids (DHETs), and epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenase hydroxylase activity. Several products of these pathways act within neurons to modulate the activities of ion channels, protein kinases, ion pumps, and neurotransmitter uptake systems, affecting processes such as cellular proliferation, inflammation, and hemostasis. The newly formed eicosanoids may also exit the cell of origin and bind to G-protein-coupled receptors present on nearby neurons or glial cells.

SMP00020

Pw000010 View Pathway
metabolic

Arginine and Proline Metabolism

Homo sapiens
This pathway (also known as Ornithine and Proline Metabolism) describes the co-metabolism of arginine, ornithine, proline, citrulline and glutamate in humans. Arginine is synthesized from citrulline by the sequential action of the cytosolic enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Citrulline can be derived from ornithine via the catabolism of proline or glutamine/glutamate. Many of the reactions required to generate proline and glutamate from ornithine are located in the mitochondria. Proline is biosynthetically derived from glutamate and its immediate precursor, 1-pyrroline-5-carboxylate. The pathways linking arginine, glutamine, and proline are bidirectional. Thus, the net utilization or production of these amino acids is highly dependent on cell type and developmental stage. On a whole-body basis, synthesis of arginine occurs principally via the intestinal–renal axis, wherein epithelial cells of the small intestine, which produce citrulline primarily from glutamine and glutamate, collaborate with the proximal tubule cells of the kidney, which extract citrulline from the circulation and convert it to arginine, which is returned to the circulation. Consequently, impairment of small bowel or renal function can reduce endogenous arginine synthesis, thereby increasing the dietary requirement. Both proline and arginine are protegenic amino acids and are incorporated into proteins by prolyl-tRNA and arginyl-tRNA, which are synthesized by their respective tRNA synthetases. Arginine can also serve as a precursor for the synthesis of creatine and phopshocreatine through the intermediate guanidoacetic acid. A key component of the arginine/proline metabolic pathway is ornithine. In epithelial cells of the small intestine, ornithine is used primarily to synthesize citrulline and arginine, in liver cells surrounding the portal vein, ornithine functions primarily as an intermediate of the urea cycle, in liver cells surrounding the central vein, ornithine is used to synthesize glutamate and glutamine while in many peripheral tissues, ornithine is used for the synthesis of glutamate and proline.

SMP00067

Pw000002 View Pathway
metabolic

Aspartate Metabolism

Homo sapiens
Aspartate synthesis in humans involves the generation of aspartate from oxaloacetate via transamination by aspartate aminotransferase or amino acid oxidase. Once synthesized, aspartate can be coupled to aspartyl tRNA via aspartyl-tRNA synthetase and used by the body in protein synthesis. The aspartate content in human proteins is about 7%. Aspartate can be converted to another polar amino acid, asparagine, via asparagine synthase. Aspartate is a precursor to many other cofactors or compounds involved in cellular signaling including N-acetyl-aspartate, beta-alanine, adenylsuccinate, arginino-succinate and N-carbamoylaspartate. Aspartate is also a metabolite in the urea cycle and participates in gluconeogenesis. Additionally, aspartate carries the reducing equivalents in the mitochondrial malate-aspartate shuttle, which utilizes the ready interconversion of aspartate and oxaloacetate. The conjugate base of L-aspartic acid, aspartate, also acts as an excitatory neurotransmitter in the brain which activates NMDA receptors.

SMP00052

Pw000161 View Pathway
metabolic

Beta Oxidation of Very Long Chain Fatty Acids

Homo sapiens
Fatty acid degradation in most organisms occurs primarily via the beta-oxidation cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes, whereas plants and most fungi harbor the beta-oxidation cycle only in the peroxisomes. In humans, fatty acid oxidation occurs in peroxisomes when the fatty acid chains are too long to be handled by the mitochondria. However, the oxidation ceases at octanyl CoA. It is believed that very long chain (greater than C-22) fatty acids undergo initial oxidation in peroxisomes which is followed by mitochondrial oxidation. One significant difference is that oxidation in peroxisomes is not coupled to ATP synthesis. Instead, the high-potential electrons are transferred to O2, which yields H2O2. The enzyme catalase, found exclusively in peroxisomes, converts the hydrogen peroxide into water and oxygen. Peroxisomal β-oxidation also requires enzymes specific to the peroxisome and to very long fatty acids. There are three key differences between the enzymes used for mitochondrial and peroxisomal β-oxidation: beta-oxidation in the peroxisome requires the use of a peroxisomal carnitine acyltransferase (instead of carnitine acyltransferase I and II used by the mitochondria) for transport of the activated acyl group into the peroxisome. The first oxidation step in the peroxisome is catalyzed by the enzyme acyl CoA oxidase. The beta-ketothiolase used in peroxisomal beta-oxidation has an altered substrate specificity, different from the mitochondrial beta-ketothiolase. In mitochondria, the beta-oxidation pathway includes four reactions that occur in repeating cycles with each fatty acid molecule. In each cycle, a fatty acid is progressively shortened by two carbons as it is oxidized and its energy captured by the reduced energy carriers NADH and FADH2. At the end of each cycle of four reactions, one acetyl-CoA two-carbon unit is released from the end of the fatty acid, which then goes through another round of beta-oxidation, continuing to oxidize and shorten even-chain fatty acids until they are entirely converted to acetyl-CoA. The acetyl-CoA generated in beta-oxidation enters the TCA cycle, where it is further oxidized to CO2, producing more reduced energy carriers, NADH and FADH2. These carriers produced in the TCA cycle, along with those produced directly in beta-oxidation, transfer their energy to the electron transport chain where they drive the creation of the proton gradient that supports mitochondrial ATP production. Another destination of acetyl-CoA is the production of ketone bodies by the liver that are transported to tissues like the heart and brain for energy.
Showing 1 - 10 of 27877 pathways