No abstract

Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid, the phosphonic analog of 3,4-dihydroxyphenylglycine, had been previously reported as a potent inhibitor of tyrosinase. The mechanism of the apparent enzyme inhibition by this compound has now been established. Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid turned out to be a substrate and was oxidized to o-quinone, which evolved to a final product identified as 3,4-dihydroxybenzaldehyde, the same as for 3,4-dihydroxyphenylglycine. Monohydroxylated compounds (amino-(3-hydroxyphenyl)methyl phosphonic acid and amino-(4-hydroxyphenyl)methyl phosphonic acid) were not oxidized, neither was 4-hydroxy-L-phenylglycine. However, the relatively high K m for amino-(3,4-dihydroxyphenyl)methyl phosphonic acid (0.52 mM) indicated that competitive inhibition could not entirely explain the previously reported strong inhibitory effect (K i ¼ 50 and 97 lM for tyrosine and 3-(3,4-dihydroxyphenyl)alanine (Dopa) as substrates, respectively). Neither was the enzyme covalently inactivated to a significant degree. Spectroscopic and electrochemical analysis of the oxidation of a mixture of Dopa and the inhibitor demonstrated that the phosphonic compound reduced dopaquinone back to Dopa, thus diminishing and delaying the formation of dopachrome. This produces an apparent strong inhibitory effect when the reaction is monitored spectrophotometrically at 475 nm. In this peculiar case Dopa acts as a redox shuttle mediating the oxidation of the shorter phosphonic homolog. Decomposition of the phosphonic o-quinone to 3,4-dihydroxybenzaldehyde drives the reaction against the slightly unfavorable difference in redox potentials.Keywords: tyrosinase; redox exchange; quinone; phosphonic amino acids; 3,4-dihydroxybenzaldehyde.Tyrosinase (EC 1.14.18.1) is a copper-containing enzyme widely distributed in nature. It catalyses the hydroxylation of monophenols to o-diphenols and the oxidation of the latter to o-quinones using molecular oxygen. Its action on the physiological substrate, L-tyrosine, produces L-3-(3,4-dihydroxyphenyl)alanine (L-Dopa) and then dopaquinone, which undergoes a series of nonenzymatic reactions leading to melanins [1]. The enzyme is responsible for melanization in animals and browning in plants. As browning in food products is an undesirable process, there has been a constant need in food industry for compounds preventing this reaction. Inhibition of mammalian tyrosinase has also been indicated as a possible approach to control human melanoma [2]. Although a large number of tyrosinase inhibitors have been described in the literature [3], the search for new natural products and synthetic compounds with such activity still continues [4]. Some of the most potent, competitive inhibitors include mimosine [5,6], tropolone [7,8], and kojic acid [9][10][11][12]. Some of us had previously shown that amino-(3,4-dihydroxyphenyl)methyl phosphonic acid, the phosphonic analog of 3,4-dihydroxyphenylglycine, was also a potent inhibitor of tyrosinase [13]. With a K i of 50 and 97 lM for tyrosin...

No abstract

Introduction. MS is characterized by a large variety of symptoms, which negatively affects the functioning and quality of life of patients. Aim. The purpose of the work is determination of the impact of Multiple Sclerosis on the daily functioning of patients and assessment of the sense of responsibility for one’s own health among patients with Multiple Sclerosis. Material and Methods. The study included 97 patients suffering from Multiple Sclerosis, treated at the Department of Neurology, University Hospital in Białystok. Study group consisted of 73 women and 24 men. The research has been conducted using the diagnostic survey method with following research tools: Activities of Daily Living scale; Instrumental Activities of Daily Living scale; Multidimensional Health Locus of Control and a self-constructed questionnaire. Results. The average age of the respondents was 52 (±10.36) and was comparable for women and men — 52.33 (±10.97) years and 51.79 (±8.42) years, respectively. The duration of the disease was on average 8 years (±3.87). Among the respondents, from the beginning of the disease, on average 5.02 exacerbations of MS (±3.08) have been observed. The most significant problem for MS patients was sphincter control (45.36%), independent bath (34.02%) and use of the toilet (31.96%). According to Lawton’s scale, patients with MS had most difficulties going out for shopping and getting outside walking distance. With the duration of the disease, the internal location of health control decreased significantly. Conclusions. As a result of increasing restrictions on the independent functioning of patients with Multiple Sclerosis, the sense of control over their own health is located in external factors such as chance and the influence of others. (JNNN 2019;8(3):102–111) Key Words: Multiple Sclerosis, health, functional status