Pathways

Carnosinemia, also known as carnosinemia, is a rare inborn error of metabolism (IEM) and recessive autosomal disorder caused by a defective CNDP1 gene which encodes for carnosinase. Carnosinase is a dipeptidase enzyme that catalyzes the breakdown of Carnosine into alanine and histidine. This disorder is characterized by secretion of large amounts of carnosine and anserine in the urine but low levels of methylhistidine. Patients also have unusually high concentrations of homocarnosine in the cerebrospinal fluid. Other symptoms include progressive neurologic disorders characterized by severe mental defect and myoclonic seizures. There is no known cure for Carnosinemia therefore treatment involves management of symptoms. There have been about 30 cases of Carnosinemia reported worldwide.

Carnosinemia, also known as carnosinemia, is a rare inborn error of metabolism (IEM) and recessive autosomal disorder caused by a defective CNDP1 gene which encodes for carnosinase. Carnosinase is a dipeptidase enzyme that catalyzes the breakdown of Carnosine into alanine and histidine. This disorder is characterized by secretion of large amounts of carnosine and anserine in the urine but low levels of methylhistidine. Patients also have unusually high concentrations of homocarnosine in the cerebrospinal fluid. Other symptoms include progressive neurologic disorders characterized by severe mental defect and myoclonic seizures. There is no known cure for Carnosinemia therefore treatment involves management of symptoms. There have been about 30 cases of Carnosinemia reported worldwide.

Carnosinemia, also known as carnosinemia, is a rare inborn error of metabolism (IEM) and recessive autosomal disorder caused by a defective CNDP1 gene which encodes for carnosinase. Carnosinase is a dipeptidase enzyme that catalyzes the breakdown of Carnosine into alanine and histidine. This disorder is characterized by secretion of large amounts of carnosine and anserine in the urine but low levels of methylhistidine. Patients also have unusually high concentrations of homocarnosine in the cerebrospinal fluid. Other symptoms include progressive neurologic disorders characterized by severe mental defect and myoclonic seizures. There is no known cure for Carnosinemia therefore treatment involves management of symptoms. There have been about 30 cases of Carnosinemia reported worldwide.

Carotenoids are terpenoids classified as orange, red or yellow fat- soluble pigments. These are responsible for the colouring of plants, such as tomatoes. Carotenoids are also essential in photosynthesis. This pathway involves many sub-pathways, such as retinol metabolism, lutein biosynthesis, the xanthophyll cycle, and abscisic acid biosynthesis. As with other terpenoid pathways, carotenoid biosynthesis begins with geranylgeranyl-PP. This takes place in the chloroplast, and the pathway continues here for almost all the subsequent reactions. Geranylgeranyl-PP is then converted to prephytoene diphosphate by using the enzyme phytoene synthase. This enzyme continues to catalyze compounds in the next reaction, using prephytoene diphosphate to produce phytoene. Phytoene is then converted to phytofluene, using the enzyme 15-cis-phytoene desaturase. Phytofluene then uses this enzyme again to create 9-cis,9'-cis-7,7',8,8'-tetrahydro-psi,psi-carotene. From here, neurosporene is created with the help of zeta-carotene desaturase. This enzyme works again to convert neurosporene to lycopene. Lycopene uses lycopene beta cyclase to become y-Carotene, which uses the same enzyme to create b-carotene. Continuing in the chloroplast, b-carotene teams up with two enzymes, beta-carotene 3-hydroxylase 1 and protein lutein deficient 5 to produce b-cryptoxanthin. These two enzymes then convert b-cryptoxanthin to zeaxanthin. This marks the beginning of the xanthophyll cycle, which end in the creation of violaxanthin, an oxygen-containing xanthophyll. From here, abscisic acid biosynthesis begins, in the cytoplasm, and ends in the endoplasmic reticulum lumen.

Carprofen (also named Rimadyl or Imadyl) is a nonsteroidal anti-inflammatory drug that can treat various joint pain or post-operative pain. Carprofen can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of Carprofen.

Carprofen is a non-steroidal anti-inflammatory drug (NSAID) used as a pain reliever in the treatment of joint pain and post-surgical pain. It is no longer used in the clinical setting, but is approved for use in dogs. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Carprofen inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain.

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Carteolol (also known as Cartrol or Ocupress) is a selective β1 adrenergic receptor antagonist (beta blocker), which can be used for treatment of high blood pressure (hypertension) and irregular heartbeats (arrhythmias). Carteolol also has the ability to mild intrinsic sympathomimetic activity (ISA) with effective range of dosage. Adrenaline (also known as epinephrine) can activate β1 adrenergic receptor so that the heart rate and output will be increased. Renin is a hormone that generated from kidney, which could lead to constriction of blood vessels. Beta blockers could efficiently prohibit renin release.

Carteolol is a cardio non-selective beta blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, carteolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, carteolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like carteolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Carteolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.