Structure, Function and Evolutionary Aspects of Mitochondria
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Mitochondrial matrix contains a wide variety of metabolites. Pyruvate, acetyl CoA, acyl CoA, α-ketoglutarate, isocitrate, succinyl CoA, succinate, malate, fumarate and oxaloacetate are involved in citric acid cycle. L-citrulline, L-ornithine and carbamoyl phosphate are used in urea cycle. Mitochondria DNA, RNA and transfer RNA are used for protein synthesis. Another ions like Ca+2, K+, Mg+2 are also present in the matrix. Moreover CO2, H2O, O2, ATP, ADP and inorganic phosphate are present as metabolites. Enzymes like citrate synthase, Pyruvate dehydrogenase, isocitrate dehydrogenase, aconitase, α-ketoglutarate dehydrogenase, succinyl CoA synthetase, fumerase and malate dehydrogenase facilitates the TCA cycle. Transaminase facilitates amino acid production. β-oxidation uses pyruvate carboxylase, acyl CoA dehydrogenase and β-ketothiolase. The urea cycle is facilitated by carbamoyl phosphate synthetase I and ornithine transcarboxylase.
Liver disease
Catherine Nelson-Piercy in Handbook of Obstetric Medicine, 2020
The usual pattern of abnormal LFTs is as follows: Moderate (less than threefold) elevation in transaminases (ALT is the most sensitive).Raised alkaline phosphatase (beyond normal pregnancy values).Raised gamma-glutamyl transpeptidase (γGT) (about 20% of cases).Mild elevation in bilirubin (less common).Increased serum total bile acid concentration.Primary bile acids (cholic acid and chenodeoxycholic acid) may increase ten to 100-fold.In some instances, an increased concentration of bile acids may be the only biochemical abnormality or raised bile acids may precede other liver function abnormality.Pruritus may precede the derangement of LFTs, or vice versa, and serial measurements are advised in women with persistent typical itching or deranged LFTs.
Gemifloxacin
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
A randomized, open-label study of community-acquired pneumonia demonstrated comparable clinical success rates for treatment with gemifloxacin 320 mg once daily and a regimen of ceftriaxone/cefuroxime axetil (with optional macrolide therapy) (Lode et al., 2002). Another study compared gemifloxacin 320 mg daily for 5 days or for 7 days in the treatment of community-acquired pneumonia (File et al., 2007). This double-blind, randomized, multinational study demonstrated non-inferiority of clinical response to the 5- versus the 7-day regimen in both the per-protocol (95.0% vs. 92.1% response) and the intention-to-treat (92.6% vs. 87.0%, p = 0.04) populations. Approximately 90% of patients in both arms had pneumonia severity scores (Fine criteria) of I or II. Rash was observed in 7/254 (2.8%) patients in the 7-day group and 1/256 (0.4%) in the 5-day group. Among the 510 enrolled patients, elevated transaminases were observed in 5–6%, diarrhea in 3%, headache or dizziness in approximately 1.5%, and nausea, hyperglycemia, or upper abdominal pain each in ≤ 1% (File et al., 2007). Gemifloxacin (320 mg daily for 7 days) was comparable to oral amoxicillin/clavulanate (1 g/125 mg three times a day for 10 days) in a randomized, double-blind study of community-acquired pneumonia in a large multicenter study in Europe and South Africa. Clinical resolution at the end of treatment was 95.3% and 90.1%, respectively, and at follow-up was 88.7% and 87.6%, respectively (Léophonte et al., 2004).
The molecular rationale for therapeutic targeting of glutamine metabolism in pulmonary hypertension
Published in Expert Opinion on Therapeutic Targets, 2019
Thomas Bertero, Dror Perk, Stephen Y. Chan
Glutamine is necessary to maintain the delicate balance of amino acid flux in the cell. Glutamine-derived non-essential amino acids make up at least half of all residues used by cultured cells in vitro for protein synthesis [20]. Proline, a major player in the production of extracellular collagen, can be produced by utilizing the carbon and nitrogen from glutamine-derived glutamate [9,56]. Likewise, the role of aspartate biosynthesis, which is closely related to glutamine flux through the TCA cycle and glutamate transamination, is crucial for cell survival. Transaminases or aminotransferases catalyze a transamination reaction between an α-keto acid and an amino acid. Aspartate appears to be a limiting amino acid for nucleotide biosynthesis in order to support cell proliferation [49,52,53], as discussed in greater detail in the context of PH below [22].
Biomarkers of neurotoxicity, oxidative stress, hepatotoxicity and lipid peroxidation in Clarias gariepinus exposed to melamine and polyvinyl chloride
Published in Biomarkers, 2020
Stanley Chidi Iheanacho, Christiana Igberi, Akunna Amadi-Eke, Delight Chinonyerem, Angus Iheanacho, Fred Avwemoya
Serum total proteins are usually synthesized in the liver and are known to be important marker of liver impairment (Iheanacho et al.2019). Significant protein reduction observed in the chemical exposed groups may suggest an increased protein breakdown as a functional response to deal with extra energy requirements needed to cope with the stress caused by the damaging effects of the toxicants. Lavanya et al. (2011) stated that reduction in protein level is usually an indication of liver damage induced by toxicants. In addition, the liver status of the exposed fish was also assessed via the activities of some intracellular enzymes (ALT, AST and ALP). AST and ALT are involved in the metabolism of amino acids and are important indicators of tissue damage in organs such as liver and kidney (Saravanan et al.2012). Elevation in transaminase activities could indicate the utilization of amino acids for oxidation or glycogenesis (elevating glycaemia as observed in the present study). Exposure to melamine caused ALT and AST elevations in Clarias batrachus (Pirarat et al.2012). Similar findings have been reported in Sparus aurata fed 0.5 g Kg−1 PVC after 30 days exposure trial (Espinosa et al.2017).
Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series
Published in Clinical Toxicology, 2022
Stephanie L. Link, Garrett Rampon, Stephen Osmon, Anthony J. Scalzo, Barry H. Rumack
An 18-year-old woman presented after intentionally ingesting 50 tablets of acetaminophen 500 mg and 12 to 24 tablets of diphenhydramine 25 mg. Her initial APAP level was 159 mcg/mL approximately four hours after ingestion. She was given IV NAC at 150 mg/kg loading dose over 1 h followed by 12.5 mg/kg/hour and transferred to a tertiary care academic hospital. Due to impaired half-life of elimination and altered kinetics of her APAP levels, and prior experience with worse outcomes and nomogram line-crossing in patients co-ingesting diphenhydramine with acetaminophen, she was administered a loading dose of fomepizole 15 mg/kg over 30 min at approximately 8 h post ingestion. Due to elevated APAP levels she received a second dose of fomepizole at hour 21. Peak transaminases were 16 U/L and 16 U/L for AST and ALT respectively. Transaminases remained normal, and the patient was transferred to inpatient psychiatry.
Related Knowledge Centers
- Amine
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- Ribosome
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- Hammerhead Ribozyme