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.
Neonatal adrenoleukodystrophy/disorders of peroxisomal biogenesis
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Hepatomegaly may be progressive [3]. Levels of transaminase activity in the blood may be elevated [3]. With time, there is little evidence of developmental progress. One patient could smile and roll from supine position at between seven and nine months, but lost these functions shortly thereafter. Another developed some lateral head movement and a smile, which she lost after 12 months [3]. One patient had a cataract [3]. Most patients have died before the second birthday [1, 3, 9]. Mean age of death of the patients was 15 months, while in classical Zellweger syndrome it was 5.7 months. In neonatal ALD, death has occurred as early as four months. A small number of patients have survived to teenage, albeit severely handicapped and dysmorphic, while some patients with infantile Refsum disease have reached adulthood [24, 25]. Impaired hearing and retinopathy have suggested a diagnosis of Usher syndrome. The mental age of patients has seldom exceeded 12 months and some have regressed at three to five years.
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).
Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women
Published in Journal of Obstetrics and Gynaecology, 2022
Sujata Siwatch, Virendra Singh, Lakhbir K. Dhaliwal, Sunita Kumari, Kartar Singh
Normal values of alanine transaminase (ALT) are <40 IU/L, of aspartate transaminase (AST) <30 IU/L and ALP <120 IU/L. Diabetes mellitus was defined according to the WHO criteria, i.e. fasting plasma glucose (FPG) ≥126 mg/dl or random plasma glucose ≥200 mg/dl or a two hour glucose tolerance test plasma glucose ≥200 mg/dl (WHO 1999). Lipids were considered as abnormal if serum high-density lipoprotein (HDL) was less than 50 mg/dl or serum triglycerides (TGs) were more than 150 mg/dl (NCEP Executive Summary 2001). Metabolic syndrome was defined by the presence of ≥3 out of 5 modified adult treatment panel III criteria. These included modified abnormal waist as per the Asia Pacific criteria, FPG >100 mg/dl or established diabetes, hypertension (i.e. blood pressure ≥130/85 mmHg or on antihypertensive drugs), HDL <50 mg/dl and serum TGs >150 mg/dl (NCEP Executive Summary 2001). According to criteria used for Asian women, women with a BMI of >25 kg/m2 were considered obese and those <25 were considered lean (WHO 2000).
Related Knowledge Centers
- Amine
- Catalysis
- Enzyme
- Ketone
- Protein
- Ribosome
- Ribozyme
- Transamination
- Amino Acid
- Hammerhead Ribozyme