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Showing 51 - 60 of 48701 pathways
SMPDB ID Pathway Chemical Compounds Proteins

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.

SMP0000128

Pw000152 View Pathway
Metabolic

Gluconeogenesis

Gluconeogenesis, which is essentially the reverse of glycolysis, results in the sythesis of glucose from non-carbohydrate substrates such as lactate, glycerol, and glucogenic amino acids. In animals, gluconeogenesis occurs primarily in the liver, and in the renal cortex to a lesser extent. This process occurs during periods of fasting or intense exercise. Gluconeogenesis is often associated with ketosis. Several non-carbohydrate carbon substrates can enter the gluconeogenesis pathway. One common substrate is lactic acid, formed during anaerobic respiration in skeletal muscle. Lactate may also come from red blood cells, which obtain energy solely from glycolysis as they have no membrane-bound organelles for aerobic respiration. Lactate is transported to the liver to be converted into pyruvate in the Cori cycle by lactate dehydrogenase. Pyruvate can then be used to generate glucose via gluconeogenesis. Many other compounds can also function as substrates for gluconeogenesis such as citric acid cycle intermediates (through conversion to oxaloacetate), amino acids other than lysine or leucine, and glycerol .

SMP0000467

Pw000169 View Pathway
Metabolic

Trehalose Degradation

Trehalose, also known as mycose or tremalose, is a sugar consisting of two 1-1 alpha bonded glucose molecules. It is produced by some plants, bacteria, fungi and invertebrates, and can be used as a source of energy, such as for flight in insects, and as a survival mechanism to avoid freezing and dehydration. After ingestion in the intestine lumen, trehalose can interact with trehalase, which exists in the brush border of the cells there. In a reaction that also requires a water molecule, it is broken. These are then transported into the epithelial cells along with a sodium ion by a sodium/glucose cotransporter, which can bring glucose up its gradient along with sodium moving down its gradient. Once inside the cell, the glucose can then be transported out of the basolateral membrane by a solute carrier family 2 facilitated glucose transporter. From there, the glucose enters the blood stream, and is transported to liver hepatocytes. Once in the liver, glucokinase can use the energy and phosphate from a molecule of ATP to form glucose-6-phosphate, which then goes on to start the process of glycolysis.

SMP0000480

Pw000171 View Pathway
Metabolic

Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids

Beta-oxidation is the major degradative pathway for fatty acid esters in humans. Fatty acids and their CoA esters are found throughout the body, playing roles such as components of cellular lipids, regulators of enzymes and membrane channels, ligands for nuclear receptors, precursor molecules for hormones, and signalling molecules. Beta-oxidation occurs in the peroxisomes and mitochondria, the latter of which is depicted here. Whether beta-oxidation starts in the mitochondria or the peroxisome depends on the length of the fatty acid. Medium to long chain fatty acids go directly to the mitochondria, whereas very long chain fatty acids (>22 carbons) may be first metabolized down to octanyl-CoA in the peroxisomes and then transported to the mitochondria for the remainder of the oxidation. Beta-oxidation begins with fatty acids first being activated by an acyl-coenzyme A synthetase. This process uses ATP to produce a reactive fatty acyl adenylate which then reacts with coenzyme A to produce a fatty acyl-CoA. Short and medium chain fatty acids can enter the mitochondria directly via diffusion where they are activated in the mitochondrial matrix by acyl-coenzyme A synthetases. Long chain fatty acids must be activated in the outer mitochondrial membrane then transported as a carnatine complex into the mitochondria. A double bond is formed between C-2 and C-3 to produce trans-Δ2-enoyl-CoA which is catalyzed by acyl-CoA-dehydrogenases in the mitochondria. Enoyl CoA hydratase then hydrates the double bond between C-2 and C-3 to produce a L-beta-hydroxyacyl CoA which then has its hydroxyl group converted to a keto group to produce beta-ketoacyl CoA. Finally, the beta-ketoacyl CoA is cleaved by beta-ketothiolase and a thiol group is inserted between C-2 and C-3 to reduce the acyl-CoA and produce acetyl-CoA. Acetyl-CoA can then enter the citric acid cycle.

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.

SMP0000055

Pw000001 View Pathway
Metabolic

Alanine Metabolism

Alanine (L-Alanine) is an α-amino acid that is used for protein biosynthesis. Approximately 8% of human proteins have alanine in their structures. The reductive lamination of pyruvate is effected by alanine transaminase. L-Alanine can be converted to pyruvic acid by alanine aminotransferase 1 reversibly coupled with interconversion of oxoglutaric acid and L-glutamic acid. L-Alanine can also be produced by alanine-glyoxylate transaminase with coupled interconversion of glyoxylate and glycine. L-Alanine will be coupled with alanyl tRNA by alanyl-tRNA synthetase to perform protein biosynthesis. Alanine can also be used to provide energy under fasting conditions. There are two pathways that can facilitate this: (1) alanine is converted to pyruvate to synthesize glucose via the gluconeogenesis pathway in liver tissue or (2) alanine converted into pyruvate moves into the TCA cycle to be oxidized in other tissues.

SMP0000035

Pw000145 View Pathway
Metabolic

Bile Acid Biosynthesis

A bile acids life begins as cholesterol is catabolized, as bile acid is a derivative of cholesterol. This pathway occurs in the liver, beginning with cholesterol being converted to 7a-hydroxycholesterol through the enzyme cholesterol-7-alpha-monooxygenase, after being transported into the liver cell. 7a-hydroxycholesterol then becomes 7a-hydroxy-cholestene-3-one, which is made possible by the enzyme 3-beta-hydroxysteroid dehydrogenase type 7. 7a-hydroxy-cholestene-3-one then is used in two different chains of reactions. The first, continuing in the liver, uses the enzyme 3-oxo-5-beta-steroid-4-deydrogenase to become 7a-hydroxy-5b-cholestan-3-one. After that, aldo-keto reductase family 1 member C4 is used to create 3a,7a-dihydroxy-5b-cholestane. In the mitochondria of the cell, sterol 26-hydroxylase converts 3a,7a-dihydroxy-5b-cholestane to 3a,7a,26-trihydroxy-5b-cholestane, which is then converted to 3a,7a-dihydroxy-5b-cholestan-26-al by the same enzyme used in the previous reaction. This enzyme is used another time, to create 3a,7a-dihydroxycoprostanic acid. Then, bile acyl-CoA synthetase teams up with 3a,7a-dihydroxycoprostanic acid to create 3a,7a-dihydroxy-5b-cholestanoyl-CoA. 3a,7a-dihydroxy-5b-cholestanoyl-CoA remains intact while alpha-methylacyl-CoA racemase moves it along through the peroxisome. Peroxisomal acyl coenzyme A oxidase 2 converts 3a,7a-dihydroxy-5b-cholestanoyl-CoA into 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA. With the help of water, peroxisomal multifunctional enzyme type 2 turns 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA into 3a,7a,24-trihydoxy-5b-cholestanoyl-CoA. This compound then uses peroxisomal multifunctional enzyme type 2 to create chenodeoxycholoyl-CoA. From there, propionyl-CoA and chenodeoxycholoyl-CoA join forces and enlist the help of non-specific lipid transfer protein to further chenodeoxycholoyl-CoAâ€TMs journey in the peroxisome. It is then transported back into intracellular space, where after its used in 3 different reactions, its derivatives interact with intestinal microflora in the extracellular space to become lithocholyltaurine, lithocholic acid glycine conjugate, and lithocholic acid. Revisiting 7a-hydroxy-cholestene-3-one, the second chain of reactions it is involved in follows a similar path as the first, moving through the mitochondria, endoplasmic reticulum and peroxisome until choloyl-CoA is formed, which then is used in three reactions so that its derivatives may leave the cell to interact with intestinal microflora and become taurodeoxycholic acid, deoxycholic acid glycine conjugate and deoxycholic acid. There are two more important components of this pathway, both depicting the breakdown of cholesterol into bile acid. These components of the pathway occur in the endoplasmic reticulum membrane, although 2 enzymes, 25-hydroxycholesterol 7-alpha-hydroxylase and sterol 26 hydroxylase, are found in the mitochondria. Bile acids play a very important part in the digestion of foods, and are responsible for the absorption of water soluble vitamins in the small intestine. Bile acids also help absorb fats into the small intestine, a crucial part of any vertebrates diet.
Showing 51 - 60 of 48701 pathways