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Showing 41 - 50 of 49833 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000123

Pw000012 View Pathway
Metabolic

Betaine Metabolism

Betaine (or trimethylglycine) is similar to choline (trimethylaminoethanol) but differs in choline's terminal carboxylic acid group trimethylglycine is reduced to a hydroxyl group. Betaine is obtained from diet as betaine or compounds containing choline in foods such as whole grains, beets and spinach. Betaine can also be synthesized from choline in the liver and kidney. First, choline is oxidized to betaine aldehyde by mitochondrial choline oxidase (choline dehydrogenase). Then, betaine aldehyde dehydrogenase oxidizes betaine aldehyde to betaine in the mitochondria or cytoplasm. In the liver, betaine functions as a methyl donor similar to choline, folic acid, S-adenosyl methionine and vitamin B12. Methyl donors are important for liver function, cellular replication and detoxification reactions. Betaine is also involved in the production of carnitine to protect from kidney damage and functions as an osmoprotectant in the inner medulla.

SMP0000479

Pw000170 View Pathway
Metabolic

Plasmalogen Synthesis

Plasmalogens are a class of phospholipids found in animals. Plasmalogens are thought to influence membrane dynamics and fatty acid levels, while also having roles in intracellular signalling and as antioxidants. Plasmalogens consist of a glycerol backbone with an vinyl-ether-linked alkyl chain at the sn-1 position, an ester-linked long-chain fatty acid at the sn-2 position, and a head group attached to the sn-3 position through a phosphodiester linkage. It is the vinyl-ether-linkage that separates plasmalogens from other phospholipids. Plasmalogen biosynthesis begins in the peroxisomes, where the integral membrane protein dihydroxyacetone phosphate acyltransferase (DHAPAT) catalyzes the esterification of the free hydroxyl group of dihydroxyacetone phosphate (DHAP) with a molecule any of long chain acyl CoA. Next, alkyl-DHAP synthase, a peroxisomal enzyme associated with DHAPAT, replaces the fatty acid on the DHAP with a long chain fatty alcohol. The third step of plasmalogen biosynthesis is catalyzed by the enzyme acyl/alkyl-DHAP reductase, which is found in the membrane of both the peroxisome and endoplasmic reticulum (ER). Acyl/alkyl-DHAP reductase uses NADPH as a cofactor to reduce the ketone of the 1-alkyl-DHAP using a classical hydride transfer mechanism. The remainder of plasmalogen synthesis occurs using enzymes in the ER. Lysophosphatidate acyltransferases (LPA-ATs) transfer the acyl component of a polyunsaturated acyl-CoA to the the 1-alkyl-DHAP, creating a 1-alkyl-2-acylglycerol 3-phosphate. The phosphate is then removed by lipid phosphate phosphohydrolase I (PAP-I), and the head group is attached by a choline/ethanolaminephosphotransferase. The majority of plasmalogens have either ethanolamine or choline as a headgroup, although a small amount of serine and inositol-linked ether-phospholipids can also be found. In the final step, the vinyl-ether linkage is created by plasmanylethanolamine desaturase, which catalyzes the formation of a double bond in the alkyl chain of the plasmalogen.

SMP0000031

Pw000055 View Pathway
Metabolic

Pentose Phosphate Pathway

The pentose phosphate pathway—also referred to in the literature as the phosphogluconate pathway, the hexose monophosphate shunt, or the pentose phosphate shunt—is involved in the generation of NADPH as well as pentose sugars. Of the total cytoplasmic NADPH used in biosynthetic reactions, a significant proportion of it is generated through the pentose phosphate pathway. Ribose 5-phosphate is also another essential product generated by this pathway which is employed in nucleotide synthesis. The pentose phosphate pathway is also involved in the digestive process as the products of nucleic acid catabolism can be metabolized through the pathway (pentose sugars are usually yielded in the breakdown) while the carbon backbones of dietary carbohydrates can be converted into glycolytic/gluconeogenic intermediates. The pentose phosphate pathway is interconnected to the glycolysis pathway through the shared use of three intermediates: glucose 6-phosphate, glyceraldehyde 3-phosphate, and fructose 6-phosphate. The pathway can be described as eight distinct reactions (see below) and is separated into an oxidative phase and a non-oxidative phase. Reactions 1-3 form the oxidative phase and generate NADPH and pentose 5-phosphate. Reactions 4-8 form the non-oxidative phase and converts pentose 5-phosphate into other pentose sugars such as ribose 5-phosphate, but generates no NADPH. The eight reactions are as follows: reaction 1 where glucose-6-phosphate 1-dehydrogenase converts glucose 6-phosphate into D-glucono-1,5-lactone 6-phosphate with NADPH formation; reaction 2 where 6-phosphogluconolactonase converts D-glucono-1,5-lactone 6-phosphate into 6-phospho-D-gluconate;reaction 3 where 6-phosophogluconate dehydrogenase converts 6-phospho-D-gluconate into ribulose 5-phosphate with NADPH formation; reaction 4 where ribulose-phosphate 3-epimerase converts ribulose 5-phosphate into xylulose 5-phosphate; reaction 5 where ribose-5-phosphate isomerase converts ribulose 5-phosphate into ribose 5-phosphate; reaction 6 where transketolase rearranges ribose 5-phosphate and xylulose 5-phosphate to form sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate; reaction 7 where transaldolase rearranges of sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate; and reaction 8 where transkelotase rearranges of xylulose 5-phosphate and erythrose 4-phosphate to form glyceraldehyde 3-phosphate and fructose-6-phosphate.

SMP0121131

Pw122411 View Pathway
Metabolic

2-Amino-3-Carboxymuconate Semialdehyde Degradation

This pathway is part of a major route of the degradation of L-tryptophan. It begins with 2-amino-3-carboxymuconate-6-semialdehyde which is generated from L-tryptophan degradation. The 2-amino-3-carboxymuconate-6-semialdehyde first is acted upon by a decarboxylase, forming 2-aminomuconic acid semialdehyde, which is then dehydrogenated by 2-aminomuconic semialdehyde dehydrogenase to form 2-aminomuconic acid. An unknown protein forms a 2-aminomuconate deaminase which forms (3E)-2-oxohex-3-enedioate, and a second unknown protein forms a 2-aminomuconate reductase, which forms oxoadipic acid from (3E)-2-oxohex-3-enedioate. Finally, within the mitochondria, oxoadipic acid is dehydrogenated and a coenzyme A is attached by the organelle’s oxoglutarate dehydrogenase complex, forming glutaryl-CoA. Glutaryl-CoA can then be further degraded.

SMP0000444

Pw000049 View Pathway
Metabolic

Lactose Synthesis

Lactose synthesis occurs only in the mammary glands, producing lactose (4-O-B-D-galactosylpyranosyl-a-D-glucopyranoside), the major sugar in milk. Lactose is created by joining two monosaccarides with a B1,4 glycosidic bond. Glucose is first converted to UDP-galactose via the enzyme galactose-1-phosphate uridylyltransferase. UDP-galactose is then transported into the Golgi by the UDP galactose translocator, an antiporter which uses facilitated transport to move UDP galactose into the Golgi and exports UMP. Once inside the Golgi, the UDP galactose and glucose (which moves into the golgi via the GLUT-1 transporter) become substrates for the lactose synthase enzyme complex, comprised of the enzymatic subunit, galactosyltransferase with its regulatory subunit, Alpha-lactalbumin. Lactose synthase creates lactose through bonding galactose from UDP to glucose through a glycosidic bond. Although GT is found in many tissues in the body, Alpha-lactalbumin is only found on the inner surface of the Golgi in the mammary glands, limiting lactose production to the mammaries.

SMP0121123

Pw122396 View Pathway
Metabolic

Arsenate Detoxification

Arsenate is a compound similar to phosphate, but containing an arsenic atom instead of the phosphorous. As such, it is treated similarly to a phosphate ion. However, if the arsenate replaces inorganic phosphates in glycolysis, it allows glycolysis to proceed, but does not generate ATP, uncoupling glycolysis. It can also bind to lipoic acid in the Krebs cycle, leading to a greater loss of ATP. Arsenate can enter into the cell via aquaporins 7 and 9, as well as facilitated glucose transporter members 1 and 4 of solute carrier family 2, and does so by diffusion. Once inside the cell, the arsenate can be converted to arsenite via the glutathione S-transferase omega-1 enzyme, or it can be converted to ribose-1-arsenate via the purine nucleoside phosphorylase. Ribose-1-arsenate then can spontaneously form arsenite through a reaction involving hydrogen and dihydrolipoate. After arsenite has been formed by either of these methods, arsenite methyltransferase catalyzes its formation into methylarsonate. From here, it forms methylarsonite via the glutathione S-transferase omega-1 enzyme again. The methylarsonite reacts with S-adenosylmethionine, catalyzed by arsenite methyltransferase, in order to become dimethylarsinate. Finally, the compound once again interacts with the glutathione S-transferase omega-1 enzyme to form dimethylarsinous acid, the final compound in this pathway.

SMP0121126

Pw122401 View Pathway
Physiological

Aldosterone from Steroidogenesis

Aldosterone is a hormone produced in the zona glomerulosa of the adrenal cortex. It's function is to act on the distal convoluted tubule and the collecting duct of the nephron to make them more permeable to sodium to allow for its reuptake (in addition to allowing potassium wasting). As a result, water follows the sodium back into the body. The water retention contributes to an increased blood volume. Angiotensin II from the circulation binds to receptors on the zona glomerulosa cell membrane, activating the G protein and triggering a signaling cascade. The end result is the activation of the steroidogenic acute regulatory (StAR) protein that permits cholesterol uptake into the mitochondria. From there, cholesterol undergoes a series of reactions in both the mitochondrion and the smooth endoplasmic reticulum (steroidogenesis) where it finally becomes aldosterone.

SMP0000224

Pw000222 View Pathway
Physiological

Neuron Function

Neurons are electrically excitable cells that process and transmit information through electrical and chemical signals. A neuron consists of a cell body, branched dendrites to receive sensory information, and a long singular axon to transmit motor information. Signals travel from the axon of one neuron to the dendrite of another via a synapse. Neurons maintain a voltage gradient across their membrane using metabolically driven ion pumps and ion channels for charge-carrying ions, including sodium (Na+), potassium (K+), chloride (Cl−), and calcium (Ca2+). The resting membrane potential (charge) of a neuron is about -70 mV because there is an accumulation of more sodium ions outside the neuron compared to the number of potassium ions inside. If the membrane potential changes by a large enough amount, an electrochemical pulse called an action potential is generated. Stimuli such as pressure, stretch, and chemical transmitters can activate a neuron by causing specific ion-channels to open, changing the membrane potential. During this period, called depolarization, the sodium channels open to allow sodium to rush into the cell which results in the membrane potential to increase. Once the interior of the neuron becomes more positively charged, the sodium channels close and the potassium channels open to allow potassium to move out of the cell to try and restore the resting membrane potential (this stage is called repolarization). There is a period of hyperpolarization after this step because the potassium channels are slow to close, thus allowing more potassium outside the cell than necessary. The resting potential is restored after the sodium-potassium pump works to exchange three sodium ions out per two potassium ions in across the plasma membrane. The action potential travels along the axon and upon reaching the end, causes neurotransmitters such as serotonin, dopamine, or norepinephrine to be released into the synapse. These neurotransmitters diffuse across the synapse and bind to receptors on the target cell, thus propagating the signal.

SMP0121009

Pw122276 View Pathway
Physiological

Kidney Function - Descending Limb of the Loop of Henle

The loop of Henle of the nephron can be separated into an ascending limb and the descending limb. The ascending limb is highly impermeable to water, but permeable to solutes. Conversely, the descending limb is highly impermeable to solutes such as sodium, but permeable to water. As solutes are being actively transported out of the ascending limb, the solutes cause in increase in osmotic pressure. This, combined with the ability for water to move freely out of the descending limb, leads to a water reabsorption into the adjacent capillary network and a high concentration of sodium in the filtrate at the descending Limb. Water moves from the descending loop to the capillary network through aquaporin channels in the cell membrane.

SMP0000587

Pw000563 View Pathway
Physiological

Angiotensin Metabolism

Angiotensin is a peptide hormone that is part of the renin-angiotensin system responsible for regulating fluid homeostasis and blood pressure. It is involved in various means to increase the body's blood pressure, hence why it is a target for many pharmceutical drugs that treat hypertension and cardiac conditions. Angiotensin II, the primary agent to inducing an increased blood pressure, is formed in the general circulation when it is cleaved from a string of precursor molecules. Angiotensinogen is converted into angiotensin I with the action of renin, an enzyme secreted from the kidneys. From there, angiotensin I is converted to the central agent, angiotensin II, with the aid of angiotensin-converting enzyme (ACE) so that it is available in the circulation to act on numerous areas in the body when an increase in blood pressure is needed. Angiotensin II can act directly on receptors on the smooth muscle cells of the tunica media layer in the blood vessel to induce vasoconstriction and a subsequent increase in blood pressure. However, it can also influence the blood pressure by aiding in an increase of the circulating blood volume. Angiotensin II can cause vasopressin to be released, which is a hormone involved in regulating water reabsorption. Vasopressin is created in the supraoptic nuclei and they travel down the neurosecretory neuron axon to be stored in the neuronal terminals within the posterior pituitary. Angiotensin II in the cerebral circulation triggers the release of vasopressin from the posterior pituitary gland. From there, vasopressin enters into the systemic blood circulation where it eventually binds to receptors on epithelial cells in the collecting ducts of the nephron. The binding of vasopressin causes vesicles of epithelial cells to fuse with the plasma membrane. These vesicles contain aquaporin II, which are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the collecting duct changes to allow for water reabsorption back into the blood circulation. Angiotensin II also has an effect on the hypothalmus, where it helps trigger a thirst sensation. Correspondingly, there will be an increase in oral water uptake into the body, which would then also increase the circulating blood volume. Another way that angiotensin II helps increase the blood volume is by acting on the adrenal cortex to stimulate aldosterone release, which is responsible for increasing sodium reuptake in the distal convoluted tubules and the collecting duct. It is formed when angiotensin II binds to receptors on the zona glomerulosa cells in the adrenal cortex, which triggers a signaling cascade that eventually activates the steroidogenic acute regulatory (StAR) protein to allow for cholesterol uptake into the mitochondria. Cholesterol then undergoes a series of reactions during steroidogenesis, which is a process that ultimately leads to the synthesis of aldosterone from cholesterol. Aldosterone then goes to act on the distal convoluted tubule and the collecting duct to make them more permeable to sodium to allow for its reuptake. Water subsequently follows sodium back into the system, which would therefore increase the circulating blood volume. In addition, potassium and hydrogen are also being excreted into the urine simultaneously to maintain the electrolyte balance.
Showing 41 - 50 of 49833 pathways