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Pre-Clinical In-Vivo and In-Vitro Methods For Evaluation of Anti-Alzheimer’s Drugs
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Shilpa A. Deshpande, Niraj S. Vyawahare
The enzyme activity is calculated using the following equation: whereA/min= Change in absorbance per minε = 1.361 ×104 M–1 cm–1b = path length (1-cm)Vt = total volume (3.1 ml)Vs = sample volume (0.4 ml)
Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Knowledge of the molecular mechanism in porphyria makes it possible to attempt influencing the frequency of episodes. One such possibility is the alteration of the coenzyme level. In acute intermittent porphyria where δ-aminolevulinic acid synthesis is disturbed, it would be logical to diminish the pyridoxine-dependent synthesis of this intermediate by using pyridoxine antagonists. Several substances have been tested, and deoxypyridoxine has been applied successfully. A structurally unrelated pyridoxine antagonist, penicillamine causes no improvement in the neurological symptoms and is associated with no clinical or biochemical changes. Another alternative lies in the inhibition of increased enzyme activity. Chlorpromazine and other drugs block the activity of several enzymes and therefore reduce the excess δ-aminolevulinic acid and porphobilinogen production and excretion. However, on returning to the proper feeding regime, porphyria reoccurs. Chloroquine has also been reported to have a beneficial effect on cutaneous hepatic porphyria, but this compound produces liver dysfunction, and this certainly argues against its use.
Peptidases and Peptides at the Blood-Brain Barrier
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
Janet Brownlees, Carvell Williams
A membrane-bound activity in porcine cerebral microvessels has tentatively been identified as carboxypeptidase N.143 The activity was shown to be inhibited by 1,10-phenanthroline and by the carboxypeptidase N inhibitor DL-2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid. This enzyme activity (pH optimum, 7) was found to cleave the kinins kallidin and bradykinin, in each case at the C-terminal Phe-Arg bond. The Km with kallidin as substrate was 26 μM. Although these peptides are known to be rapidly inactivated in the pulmonary circulation by ACE, their dilating effects on cerebral blood vessels are apparently not enhanced by inhibitors of ACE.144 In view of this, and of the fact that the des-(C-terminal Arg) derivatives of these kinins have vasoconstricting properties,145 it has been suggested that this carboxypeptidase may play a role in modulating the cerebrovascular effects of the kinins on the cerebral circulation.143 However, receptors for the C-terminally truncated forms of kallidin and bradykinin have been identified only tentatively.146 Cultured endothelia from bovine microvessels were found to slowly convert arginine-vasopressin (1–8) to the 1–7 fragment and this was attributed to the presence of a carboxypeptidase.55
Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Prompted to “write a definition of mixed-type enzyme inhibition”, ChatGPT elaborated the following composition: Mixed-type enzyme inhibition is a form of enzyme inhibition where the inhibitor can bind to both the free enzyme and the enzyme-substrate complex, resulting in distinct effects on both the enzyme’s catalytic activity and its affinity for the substrate. In mixed-type inhibition, the inhibitor can interact with the enzyme at either the active or a separate allosteric site. […]Mixed-type enzyme inhibition is a complex regulatory mechanism that can have important implications in various biological processes and the development of therapeutic strategies targeting enzyme activity. Understanding the nature of mixed-type inhibition is crucial for studying enzyme kinetics, drug discovery, and the design of effective enzyme inhibitors. Because the algorithms of ChatGPT have been trained using a massive amount of text data, the response it provided can be considered as a representative description of mixed inhibition that aligns with the general understanding presented in articles, books and other scientific publications.
Inhibition of Echis ocellatus venom metalloprotease by flavonoid-rich ethyl acetate sub-fraction of Moringa oleifera (Lam.) leaves: in vitro and in silico approaches
Published in Toxin Reviews, 2022
Akindele Oluwatosin Adeyi, Kaosarat Keji Mustapha, Babafemi Siji Ajisebiola, Olubisi Esther Adeyi, Damilohun Samuel Metibemu, Raphael Emuebie Okonji
The effects of temperature on enzyme activity were carried out between 30 °C and 100 °C. The assay mixture was first incubated at the selected temperature for 10 min before the reaction was initiated by the addition of 50 µl enzyme that had been incubated at the same temperature. For heat stability of the enzyme, an aliquot of the enzyme was taken and incubated at temperatures of 40, 50, 60, 70, and 80 °C for a period of 1 h and at intervals of 10 min, the enzyme was taken and assayed for residual activity. The effect of pH on metalloproteinase activity was assayed at different pH values. The pH values were varied by using buffers of different pH, which includes 0.01 M citrate buffer (pH 3.0–5.0), 0.01 M Phosphate buffer (pH 6.0–7.0), 1 mM Tris buffer (pH 8.0) and borate buffer (pH 9.0–10.0). Reaction mixture each contained 1 mM of a different buffer, 0.33 M of arginine, and 0.05 ml of the enzyme (Lee et al.2014).
The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling
Published in Drug and Chemical Toxicology, 2022
Fatemeh Saberi, Farideh Bahrami, Mehdi Saberi, Mahdi Mashhadi Akbar Boojar
At different time intervals (15, 20, 30 minutes and 1, 2, 4, 8 and 24 h) post minimum toxic dose of DZ (30 mg/kg) injection (i.p.), the animals (five animals per time point) were anesthetized with diethyl ether and a sample of the heart blood was withdrawn into a heparinized glass test tube. The red cells were separated by centrifugation (8000 rpm or 2000 g) and after three times washing with phosphate buffer solution (PBS) (pH = 7.7), the blood cholinesterase activity (ChE) was assayed according to the method of Ellman and colleagues with minor modification (Bajgar et al. 2007). Briefly, the activity measurements were carried out at 25 °C in 100 mM phosphate buffer (pH = 7.4) and 0.42 mM (2, 2′-dinitro 5,5′-dithio-dibenzoic acid) DTNB (Ellman’s reagent) using 1 mM acetylthiocholine (final concentration) as the -substrate. One unit of enzyme activity was defined as the amount of enzyme that hydrolyzes 1 μM of the substrate at 25 °C. The specific activity of the enzyme was obtained by dividing enzyme activity to the protein concentration. Protein contents were determined by the method of Bradford (Bradford 1976), using bovine serum albumin as the standard. The ChE activity was expressed as a percentage of control (Askar et al. 2011).