Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although L-carnitine is not considered as an essential nutrient, endogenous synthesis may fail to ensure adequate L-carnitine levels in neonates, especially those born prematurely. Free L-carnitine is found in many foods, mainly those from animal sources. Absorption of free L-carnitine is virtually complete. Lysine and methionine are necessary ingredients for the biosynthesis of L-carnitine. All tissues in the body can produce deoxy-carnitine but, in humans, the enzyme that enables hydroxylation of deoxy-carnitine to carnitine is found only in the liver, brain and kidneys. Complex exchanges of carnitine and its precursors occur between tissues. Muscles take up carnitine from the bloodstream and contain most of the body carnitine stores. L-carnitine and L-carnitine esters are eliminated mainly through the kidneys, which may play a central role in the homeostasis of this compound. Thyroid hormones adrenocorticotrophin (ACTH), and diet all influence urinary excretion of L-carnitine. Free L-carnitine can be assayed in plasma and urine and is occasionally measured in muscle biopsy specimens. Plasma L-carnitine levels may not accurately reflect L-carnitine body stores. L-carnitine ensures transfer of fatty acids to the mitochondria where they undergo oxidation. This process is associated with production of short-chain acylcarnitine which exit from the mitochondria or peroxisomes. L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L-carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common. Currently, these deficiencies are classified into two groups. In deficiencies with myopathy, only the muscles are deficient in L-carnitine, perhaps as a result of a primary anomaly of the L-carnitine transport system in muscles. In systemic deficiencies, L-carnitine levels are low in the plasma and in all body tissues. Systemic L-carnitine deficiencies are usually the result of a variety of disease states including deficient intake in premature infants or long-term parenteral nutrition; renal failure; organic acidemias; and Reye's syndrome. Modifications in L-carnitine metabolism have also been reported in patients with diabetes mellitus, malignancies, myocardial ischemia, and alcohol abuse. A large number of supplementation trials have been carried out.
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PMID:[L-carnitine: metabolism, functions and value in pathology]. 129 65

The parameters of lipid peroxidation (LPO) and hepatic monooxygenase function (HMF) were studied in 92 patients with coronary heart disease (CHD). After termination of and within the first 24 hours after myocardial revascularization, the levels of malonic dialdehyde and conjugate trienes were found to show 45.6 and 62.1% increases, respectively. The half-life of antipyrine (AP T(1/2)) increased by 23.5%. Studies on postoperative days 3-4 and 10-12 revealed a reduction in LPO rates and normalized HMF. After off-pump surgery, LPO and HMF significantly unchanged. On the contrary, open heart surgery resulted in a noticeable activation of LPO and an almost 1.5-fold decrease in HMF. The increase in oxidative stress and the deceleration of hepatic microsomal oxidation were ascertained to be directly related to the duration of extracorporeal circulation and the time of myocardial ischemia. After surgery, the rate of LPO and the reduction of HMF were more considerable in patients with multiple organ dysfunctions, as compared with the uncomplicated postoperative period. Within the first 24 hours following surgery, AP T(1/2) increased by 83.4%, but on postoperative days 10 to 14, it remained to be decreased by almost 1.5 times as compared with the baseline. Thus, LPO activation is one of the leading mechanisms of decelerated hepatic xenobiotic biotransformation after myocardial revascularization. Diminished lower HMF enhances the sensitivity of CHD patients to drug therapy and requires a differential approach to its use.
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PMID:[Oxidative stress and hepatic monooxygenase function in patients with coronary heart disease before and after cardiac surgery]. 1805 92

Aldose reductase (AR) is a multi-functional AKR (AKR1B1) that catalyzes the reduction of a wide range of endogenous and xenobiotic aldehydes and their glutathione conjugates with high efficiency. Previous studies from our laboratory show that AR protects against myocardial ischemia-reperfusion injury, however, the mechanisms by which it confers cardioprotection remain unknown. Because AR metabolizes aldehydes generated from lipid peroxidation, we tested the hypothesis that it protects against ischemic injury by preventing ER stress induced by excessive accumulation of aldehyde-modified proteins in the ischemic heart. In cell culture experiments, exposure to model lipid peroxidation aldehydes-4-hydroxy-trans-2-nonenal (HNE), 1-palmitoyl-2-oxovaleroyl phosphatidylcholine (POVPC) or acrolein led to an increase in the phosphorylation of ER stress markers PERK and eIF2-alpha and an increase in ATF3. The reduced metabolite of POVPC 1-palmitoyl-2-hydroxyvaleroyl phosphatidylcholine (PHVPC) was unable to stimulate JNK phosphorylation. No increase in phospho-eIF2-alpha, ATF3 or phospho-PERK was observed in cells treated with the reduced HNE metabolite 1,4-dihydroxynonenol (DHN). Lysates prepared from isolated perfused mouse hearts subjected to 15 min of global ischemia followed by 30 min of reperfusion ex vivo showed greater phosphorylation of PERK and eIF2-alpha than hearts subjected to aerobic perfusion alone. Ischemia-induced increases in phospho-PERK and phospho-eIF2-alpha were diminished in the hearts of cardiomyocyte-specific transgenic mice overexpressing the AR transgene. These observations support the notion that by removing aldehydic products of lipid peroxidation, AR decreases ischemia-reperfusion injury by diminishing ER stress.
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PMID:Aldose reductase decreases endoplasmic reticulum stress in ischemic hearts. 1904 36