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Fatty Acid Oxidation Inhibitor
Fatty acid oxidation inhibitors are a new potent class of drugs used in treatment of stable angina pectoris and an addition in treatment of chronic heart failure. Drugs * CPT-I inhibitors: Etomoxir, Oxfenicine, Perhexiline CPT-I ( carnitine palmitoyl transferase) converts fatty acyl-CoA to fatty acyl-carnitine. * Carnitine biosynthesis inhibitor: Mildronate * 3-KAT inhibitors: Trimetazidine 3-KAT (3-ketoacyl-coenzyme A thiolase) inhibitors directly inhibits fatty acid beta-oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle .... * pFOX directly inhibits fatty acid beta-oxidation.Partial fatty acid oxidation inhibitors: a potentially new class of drugs for heart failure; European Journal of Heart Failure 4 2002. 3-6; http://eurjhf.oxfordjournals.org/content/4/1/3.full.pdf+h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angina Pectoris
Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstruction or spasm of the arteries that supply blood to the heart muscle. The main mechanism of coronary artery obstruction is atherosclerosis as part of coronary artery disease. Other causes of angina include abnormal heart rhythms, heart failure and, less commonly, anemia. The term derives from the Latin ''angere'' ("to strangle") and ''pectus'' ("chest"), and can therefore be translated as "a strangling feeling in the chest". There is a weak relationship between severity of angina and degree of oxygen deprivation in the heart muscle, however, the severity of angina does not always match the degree of oxygen deprivation to the heart or the risk of a myocardial infarction (heart attack). Some people may experience severe pain even thou ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heart Failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is measured by the severity of symptoms during exercise. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease. Common causes of heart failure include coronary artery disease, heart attack, high blood pressure, atrial fibrillation, valvular heart disease, excessive alcohol consumption, infection, and cardiomyopathy. These cause heart failure by alteri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Etomoxir
Etomoxir, or 2 (4-chlorophenoxy)hexylxirane-2-carboxylate, is an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) on the inner face of the outer mitochondrial membrane. This prevents the formation of acyl carnitines, a step that is necessary for the transport of fatty acyl chains from the cytosol into the intermembrane space of the mitochondria. This step is essential to the production of ATP from fatty acid oxidation. Etomoxir has also been identified as a direct agonist of PPARα. An off-target effect has been demonstrated at high concentrations of etomoxir on Coenzyme-A (CoA) metabolism. A double-blind crossover study in human adult males showed that treatment with etomoxir enhanced feelings of hunger and increased meal portion size by 22%. Etomoxir has been reported to decrease the incorporation of palmitic acid and oleic acid into cardiolipin, although it does not affect the activities of cardiolipin biosynthesis and remodeling. Etomoxir has off-target ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Perhexiline
Perhexiline (Pexsig) is a prophylactic antianginal agent used primarily in Australia and New Zealand. Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O2 consumption and consequently increases myocardial efficiency. Its clinical use has been limited by its narrow therapeutic index and high inter- and intra-individual pharmacokinetic variability. It was outlawed in many countries due to its adverse effects on poor metabolisers (PM). The product has been reintroduced for patients who have contraindications, or have not responded to other treatments for angina. Perhexiline metabolism The major route of perhexiline metabolism in humans is hydroxylation by microsomal CYP2D6.Sørensen, L. B., Sørensen, R. N., Miners, J. O., ''et al.'', Polymorphic hydroxylation of perhexiline ''in vitro''. ''British Journal of Cl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine Palmitoyl Transferase
Carnitine O-palmitoyltransferase (also called carnitine palmitoyltransferase) is a mitochondrial transferase enzyme () involved in the metabolism of palmitoylcarnitine into palmitoyl-CoA. A related transferase is carnitine acyltransferase. Molecules Image:Palmitoylcarnitine.PNG , Palmitoylcarnitine Image:Palmitoyl coenzyme A.svg, Palmitoyl CoA Pathway Human forms There are four different forms of CPT in humans: * CPT1A – associated with Carnitine palmitoyltransferase I deficiency * CPT1B * CPT1C * CPT2 – associated with carnitine palmitoyltransferase II deficiency See also * References External links * – Acyltransferases ChoActase / COT / CPT family in PROSITE Choline/Carnitine o-acyltransferase familyin Pfam Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 35.0, was released in November 2021 and contains 19,632 families. Uses ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carnitine Biosynthesis
Carnitine biosynthesis is a method for the endogenous production of L-carnitine, a molecule that is essential for energy metabolism. In humans and many other animals, L-carnitine is obtained from both diet and by biosynthesis. The carnitine biosynthesis pathway is highly conserved among many eukaryotes and some prokaryotes. L-Carnitine is biosynthesized from ''N''ε-trimethyllysine. At least four enzymes are involved in the overall biosynthetic pathway. They are ''N''ε-trimethyllysine hydroxylase, 3-hydroxy-''N''ε-trimethyllysine aldolase, 4-''N''-trimethylaminobutyraldehyde dehydrogenase and γ-butyrobetaine hydroxylase. ''N''ε-Trimethyllysine hydroxylase The first enzyme of the L-carnitine biosynthetic pathway is ''N''ε-trimethyllysine hydroxylase, an iron and 2-oxoglutarate (2OG)-dependent oxygenase that also requires ascorbate. ''N''ε-trimethyllysine hydroxylase catalyses the hydroxylation reaction of ''N''ε-trimethyllysine to 3-hydroxy-''N''ε-trimethyllys ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mildronate
Meldonium (INN; trade name Mildronate, among others) is a limited-market pharmaceutical, developed in 1970 by Ivars Kalviņš at the USSR Latvia Institute of Organic Synthesis, and now manufactured by the Latvian pharmaceutical company Grindeks and several generic manufacturers. It is primarily distributed in Eastern European countries as an anti-ischemia medication. Since 1 January 2016, it has been on the World Anti-Doping Agency (WADA) list of substances banned from use by athletes. Meldonium can be used as a metabolic modulator, changing how some hormones accelerate or slow down enzymatic reactions in the body. However, there are debates over its use as an athletic performance enhancer. Some athletes are known to have used meldonium before it was banned. Nevertheless, many athletes have been suspended or disqualified officially in relation to this drug. Medical use Meldonium may be used to treat coronary artery disease. These heart problems may sometimes lead to is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Trimetazidine
Trimetazidine ( IUPAC: 1-(2,3,4-trimethoxybenzyl)piperazine) is a drug for angina pectoris (chest pain associated with blood flow to the heart) sold under many brand names. Trimetazidine is described as the first cytoprotective anti-ischemic agent developed and marketed by Laboratoires Servier (France). It is an anti-ischemic (antianginal) metabolic agent of the fatty acid oxidation inhibitor class, meaning that it improves myocardial glucose utilization through inhibition of fatty acid metabolism. Medical uses Trimetazidine is usually prescribed as a long-term treatment of angina pectoris, and in some countries (including France) for tinnitus and dizziness. It is taken twice a day. In 2012, the European Medicines Agency (EMA) finished a review of benefits and risks of trimetazidine and recommended restricting use of trimetazidine-containing medicines to just as an additional treatment of angina pectoris in cases of inadequate control by or intolerance to first-line a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Beta Oxidation
In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes. The overall reaction for one cycle of beta oxidation is: :C''n''-acyl-CoA + FAD + + + CoA → C''n''-2-acyl-CoA + + NADH + + acetyl-CoA Activation and membrane transport Free fatty acids cannot penetrate any biological membrane due to their negative charge. Free fatty acids must cross the cell membrane through specific transport ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
