Molecular Structure and Functions of Collagen
Marcel E. Nimni in Collagen, 1988
Somewhere in the process of extrusion, recently formed microfibrils must be recognized by the enzyme lysyl oxydase, which converts certain peptide-bound lysines and hydroxylysines to aldehydes. This enzyme initiates the biosynthesis of cross-links in collagen. Recent reviews summarized most of our knowledge in this field.59,60 This enzyme, first described by Pinnell and Martin,61 catalyzes the oxidative deamination of lysine and hydroxylysine. The enzyme is an extracellular amine oxidase and has been purified from a variety of connective tissues. The molecular weight in most species is 30,000 daltons or a multiple thereof. It requires Cu2+ and probably pyridoxal as cofactors, and molecular oxygen seems to be the cosubstrate and hydrogen acceptor. It is irreversibly inhibited by the lathyrogen BAPN. This enzyme exhibits maximal activity when acting on reconstituted collagen fibers rather than upon monomeric collagen. Because of this it is felt that the enzyme is most likely to act upon microfibrillar aggregates of collagen molecules at the time of extrusion. It would be difficult to conceive how it could act otherwise on collagen, since once assembled into the quarter-staggered array and compacted into fibers, it would be difficult for the enzyme to gain access to the interior of the fiber.
Therapeutic Nutrition
W. John Diamond in The Clinical Practice of Complementary, Alternative, and Western Medicine, 2017
The Phase I detoxification reaction is primarily a functionalization reaction, that is, it adds a functional group to the fat soluble substance by means of oxidation, reduction, or hydrolysis. These enzymes are membrane associated. There are two enzyme systems that are responsible for these reactions. The cytochrome P-450 monoxygense system is the first enzymatic line of defense against all foreign compounds, the predominant detoxification system, and responsible for most drug biotransformation. This system is composed of at least ten isoenzymes, each having a slightly different reactive profile and having affinity for a different drug or xenobiotic. This system is also important in the detoxification of endogenous active biological molecules such as steroids. The mixed-function amine oxidase system is used only for those compounds that fit the enzyme profile.
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Phenylalanine inhibits tryptophan hydroxylase by reducing the transfer of tryptophan across the nerve ending membranes. Subsequently, the transformation of tryptophan to serotonin becomes deficient. Serotonin plays a role in the synaptic transmission of certain areas of the brain, and therefore, the decrease of serotonin synthesis may be another plausible cause of mental retardation. The administration of serotonin can counteract the toxic action of high phenylalanine levels in the brain. Phenylethylamine can be an immediate causative factor also. This compound is formed in phenylketonurics when the concentration of phenylalanine is high, and particularly when further oxidation is inhibited. Amine oxidase inhibitors bring about an aggravation of neurological symptoms. It may be that an interaction between the mechanisms responsible for the mental effects depends on the degree of maturation of the nervous system.
Exploring the activity of polyamine analogues on polyamine and spermine oxidase: methoctramine, a potent and selective inhibitor of polyamine oxidase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Maria Luisa Di Paolo, Manuela Cervelli, Paolo Mariottini, Alessia Leonetti, Fabio Polticelli, Michela Rosini, Andrea Milelli, Filippo Basagni, Rina Venerando, Enzo Agostinelli, Anna Minarini
Amine oxidase activity was determined by measuring the H2O2 generation rate with a peroxidase-coupled continuous assay. Amplex Red reagent was used as fluorogenic substrate for horseradish peroxidase52. All experiments were carried out in Hepes 50 mM, at pH 7.5 and 37 °C. Phosphate buffer was not used, in order to avoid the possible formation of phosphate-SPM derivative complexes53. Assays were carried out in a final volume of 800 μl, in the presence of Amplex Red (100 μM) and horseradish peroxidase type II (5 U/ml). The assay solutions containing SMOX or PAOX were pre-incubated for 2 min (in the presence or absence of the various compounds); the substrate was then added and the reaction was run continuously for 3 min. Spermine and N1AcSPM were used as substrates for SMOX and PAOX, respectively. Enzyme assay concentrations were 0.5 μg/ml and 0.3 μg/ml for PAOX and SMOX respectively, unless otherwise specified.
HPLC–UV assay for the evaluation of inhibitors of plasma amine oxidase using crude bovine plasma
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Kira Mergemeier, Florian Galster, Matthias Lehr
Plasma amine oxidase (PAO) is a topaquinone- and copper-dependent oxidase, which converts primary amines to aldehydes with the concomitant production of ammonia and hydrogen peroxide1. The enzyme, which is also known as copper-containing amine oxidase 3 (AOC3), semicarbazide-sensitive amine oxidase (SSAO) or vascular adhesion protein-1 (VAP-1), is mainly expressed in endothelial cells of blood vessels, smooth muscle cells, and adipocytes. Besides, a soluble form is found in blood plasma, resulting from proteolytic cleavage of membrane-bound vascular PAO2–4. The enzyme participates in several physiological and pathophysiological processes5–7. In particular, it functions as a vascular adhesion protein that mediates recruitment and extravasation of leukocytes at sites of inflammation8,9. Furthermore, it is involved in glucose transport in adipose cells. Because of the production of reactive aldehydes and hydrogen peroxide, PAO activity is linked to cellular damage in diabetes. Thus, inhibitors of this enzyme could be of therapeutic value in the treatment of inflammatory diseases and diabetic complications10,11.
Polyamine biomarkers as indicators of human disease
Published in Biomarkers, 2021
Mohsin Amin, Shiying Tang, Liliana Shalamanova, Rebecca L. Taylor, Stephen Wylie, Badr M. Abdullah, Kathryn A. Whitehead
In the blood, the increased levels of polyamines directly reflect the exacerbated levels of polyamine synthesis, which exist as a result of cancer tissues augmenting the synthetic abilities of amine oxidase enzymes (Sun et al.2017). Such is evident in instances of breast cancer whereby, increased proliferation and progression of breast cancer, in part, is stimulated by overexpression of polyamine synthesis. Breast cancer is one of the most common malignancies which affects women, in the western world (Torre et al.2017). ODC, a polyamine decarboxylating enzyme, has been detected at increased levels in breast cancer (2.42 nmol CO2/h g), in comparison to benign tumours (0.62 nmol CO2/h g) (Cañizares et al.1999). This suggests that increased polyamine levels may contribute towards the active disease and therefore such biomarkers in the blood may allow valuable diagnostic measurements for the differentiation between active and inactive cancers. Furthermore, ODC has been recognized as an independent prognostic factor for localized breast cancer, and successful attempts at blocking polyamine receptors on ODC have been shown to provide a beneficial impact on the implications of breast cancer treatment (Jun et al.2007).