scholarly journals Enzymatically Produced Trimethylamine N-Oxide: Conserving It or Eliminating It

Catalysts ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1028 ◽  
Author(s):  
Gianluca Catucci ◽  
Giulia Querio ◽  
Sheila J. Sadeghi ◽  
Gianfranco Gilardi ◽  
Renzo Levi
Keyword(s):  
Marine Mammals ◽  
Hydrostatic Stress ◽  
Physiological Role ◽  
Health Conditions ◽  
Renal Diseases ◽  
Drug Metabolizing Enzyme ◽  
Long Time ◽  
Metabolizing Enzyme ◽  
Very High

Trimethylamine N-Oxide (TMAO) is the product of the monooxygenation reaction catalyzed by a drug-metabolizing enzyme, human flavin-containing monooxygenase 3 (hFMO3), and its animal orthologues. For several years, researchers have looked at TMAO and hFMO3 as two distinct molecules playing specific but separate roles, the former to defend saltwater animals from osmotic or hydrostatic stress and the latter to process xenobiotics in men. The presence of high levels of plasmatic TMAO in elasmobranchs and other animals was demonstrated a long time ago, whereas the actual physiological role of hFMO3 is still unknown because the enzyme has been mainly characterized for its ability to oxidize drugs. Recently TMAO was found to be related to several human health conditions such as atherosclerosis, cardiovascular, and renal diseases. This correlation poses a striking question of how other vertebrates (and invertebrates) can survive in the presence of very high TMAO concentrations (micromolar in humans, millimolar in marine mammals and several hundred millimolar in elasmobranchs). Therefore, it is important to address how TMAO, its precursors, and FMO catalytic activity are interconnected.

scholarly journals Kinins and Kinin Receptors in Cardiovascular and Renal Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 240
Author(s):  
Jean-Pierre Girolami ◽  
Nadine Bouby ◽  
Christine Richer-Giudicelli ◽  
Francois Alhenc-Gelas
Keyword(s):  
Experimental Studies ◽  
Physiological Role ◽  
Renal Diseases ◽  
Kinin System ◽  
Genetic Studies ◽  
Pharmacological Manipulation ◽  
Kininase Ii ◽  
Kinin Receptors ◽  
Kallikrein Kinin System

This review addresses the physiological role of the kallikrein–kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.

scholarly journals The role of nitric oxide on decreasing the hepatic drug metabolizing enzyme activity by bacterial endotoxin in rats

1999 ◽  
Vol 79 ◽  
pp. 125
Author(s):  
Kiyoyuki Kitaichi ◽  
Li Wang ◽  
Haruna Kidokoro ◽  
Mitsunori Iwase ◽  
Kenji Takagi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Enzyme Activity ◽  
Bacterial Endotoxin ◽  
Hepatic Drug ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

scholarly journals The role of cytochrome P-450 in cholesterol biogenesis and catabolism

1972 ◽  
Vol 128 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Sandra D. Atkin ◽  
Eileen D. Palmer ◽  
P. D. English ◽  
B. Morgan ◽  
M. A. Cawthorne ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Carbon Disulphide ◽  
Normal Serum ◽  
Liver Cholesterol ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cytochrome P 450

1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [14C]acetate or [14C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7α-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7α-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.

Luminal glucose concentrations in the gut under normal conditions

1990 ◽  
Vol 259 (5) ◽  
pp. G822-G837 ◽  
Author(s):  
R. P. Ferraris ◽  
S. Yasharpour ◽  
K. C. Lloyd ◽  
R. Mirzayan ◽  
J. M. Diamond
Keyword(s):  
Absorptive Capacity ◽  
Physiological Role ◽  
Solvent Drag ◽  
Direct Infusion ◽  
Rat Stomach ◽  
Osmotic Water ◽  
Major Mode ◽  
The Face ◽  
Very High

Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

scholarly journals Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1969
Author(s):  
Sonia Levi ◽  
Maddalena Ripamonti ◽  
Marko Dardi ◽  
Anna Cozzi ◽  
Paolo Santambrogio
Keyword(s):  
Physiological Condition ◽  
Physiological Role ◽  
Biochemical Properties ◽  
Cross Reactivity ◽  
Pathological Conditions ◽  
Human Ferritin ◽  
Ferritin Gene ◽  
New Type ◽  
Very High

In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed.

scholarly journals Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18046 ◽  
Author(s):  
Binu Shrestha ◽  
J. Michael Reed ◽  
Philip T. Starks ◽  
Gretchen E. Kaufman ◽  
Jared V. Goldstone ◽  
...  
Keyword(s):  
Domestic Cat ◽  
Enzyme Defect ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Major Drug

scholarly journals Control of δ-aminolaevulinate synthase and haem oxygenase in chroniciron-overloaded rats

1981 ◽  
Vol 200 (1) ◽  
pp. 35-42 ◽  
Author(s):  
N G Ibrahim ◽  
J C Nelson ◽  
R D Levere
Keyword(s):  
Iron Overload ◽  
Inborn Errors ◽  
Cellular Iron ◽  
Drug Metabolizing Enzyme ◽  
Oxygenase Activity ◽  
Exogenous Agents ◽  
Haem Oxygenase ◽  
Metabolizing Enzyme ◽  
Cytochrome P 450

The hepatic porphyrias are inborn errors of porphyrin and haem biosynthesis characterized biochemically by excessive excretion of delta-aminolaevulinate (ALA), porphobilinogen and other intermediates in haem synthesis. Clinical evidence has implicated iron in the pathogenesis of several types of genetically transmitted diseases. We investigated the role of iron in haem metabolism as well as its relationship to drug-mediated induction of ALA synthase and haem oxygenase in acute and chronic iron overload. Acute iron overload in rats resulted in a marked increase in hepatic haem oxygenase that was associated with a decrease in cytochrome P-450 and an increase in ALA synthase activity. Aminopyrine N-demethylase and aniline hydroxylase activities, which are dependent on the concentration of cytochrome P-450, were also decreased. In contrast, in chronic-iron-overloaded rats, there was an adaptive increase in haem oxygenase activity and an increase in ALA synthase that was associated with normal concentrations of microsomal haem and cytochrome P-450. The induction of ALA synthase in chronic iron overload was enhanced by phenobarbital and allylisopropylacetamide, in spite of the fact that these agents did not increase haem oxygenase activity. Small doses of Co2+ were potent inducers of the haem oxygenase in chronic-iron-overloaded, but not in control, animals. We conclude that increased hepatic cellular iron may predispose certain enzymes of haem synthesis to induction by exogenous agents and thereby affect drug-metabolizing enzyme activities.

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