Hydrolysis of Sialic Acids and O-Acetylated Sialic Acids with Propionic Acid

Abstract N-acetylneuraminic acid (5-acetamido-3,5-dideoxy-d-glycero-d-galacto-non-2-ulosonic acid), which is the principal sialic acid family member of the non-2-ulosonic acids and their various derivatives, is often found at the terminal position on the glycan chains that adorn all vertebrate cells. This terminal position combined with subtle variations in structure and linkage to the underlying glycan chains between humans and other mammals points to the importance of this diverse group of nine-carbon sugars as indicators of the unique aspects of human evolution and is relevant to understanding an array of human conditions. Enzymes that catalyze the removal N-acetylneuraminic acid from glycoconjugates are called neuraminidases. However, despite their documented role in numerous diseases, due to the promiscuous activity of many neuraminidases, our knowledge of the functions and metabolism of many sialic acids and the effect of the attachment to cellular glycans is limited. To this end, through a concerted effort of generation of random and site-directed mutagenesis libraries, subsequent screens and positive and negative evolutionary selection protocols, we succeeded in identifying three enzyme variants of the neuraminidase from the soil bacterium Micromonospora viridifaciens with markedly altered specificity for the hydrolysis of natural Kdn (3-deoxy-d-glycero-d-galacto-non-2-ulosonic acid) glycosidic linkages compared to those of N-acetylneuraminic acid. These variants catalyze the hydrolysis of Kdn-containing disaccharides with catalytic efficiencies (second-order rate constants: kcat/Km) of greater than 105 M−1 s−1; the best variant displayed an efficiency of >106 M−1 s−1 at its optimal pH.

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Limited Hydrolysis of Polysialic Acid by Human Neuraminidase Enzymes

10.26434/chemrxiv.14065025.v1 ◽

2021 ◽

Author(s):

Carmanah D. Hunter ◽

Christopher Cairo

Keyword(s):

Polysialic Acid ◽

Chemical Properties ◽

Sialic Acids ◽

Degree Of Polymerization ◽

Health And Disease ◽

Substrate Tolerance ◽

The Impact ◽

Hydrolysis Of ◽

Unique Chemical

Regulation of sialic acids by human neuraminidase (hNEU) enzymes is important to many biological processes. Defining hNEU substrate tolerance can help to elucidate the roles of these enzymes in regulating sialosides in human health and disease. Polysialic acid (polySia) is a polyanion of α(2→8) linked sialic acids with roles in nervous, reproductive, and immune systems and is dysregulated in some malignancies and mental disorders. The unique chemical properties of this polymer, which include an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its study. Herein we describe the first systematic study of hNEU isoenzyme activity towards polysialic acid in vitro. The experimental design allowed us to study the impact of several factors that may influence polysialic acid degradation including pH, polymer size, and the relative ionic strength of the surrounding media. We report that short chains of polysialic acid (degree of polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not at neutral pH. No hNEU-catalyzed hydrolysis of longer polymers (DP 10-20) was detected. These findings suggest a neuraminidase-independent mechanism for polysialic acid turnover such as internalization and degradation in endosomes and lysosomes.

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The Inhibitory Effect of Sialic Acid on Fibrinolysis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654081 ◽

1967 ◽

Vol 17 (01/02) ◽

pp. 023-030 ◽

Cited By ~ 1

Author(s):

H Rubin ◽

N. D Ritz

Keyword(s):

Sialic Acid ◽

Inhibitory Effect ◽

Sialic Acids ◽

Normal Serum ◽

The Body ◽

Inhibitory Effects ◽

Acetylneuraminic Acid ◽

Heated Plates ◽

Hydrolysis Of ◽

Fibrinolytic Action

SummaryThe inhibitory effect of N-acetylneuraminic acid and glycolyl neuramaminic acids on the hydrolysis of 51Cr tagged casein by plasmin and α-chymotrypsin has been demonstrated. N,O-diacetylneuraminic acid was ineffective. The inhibitory effect was increased by an increase in ionic strength of the reaction mixture. The two active sialic acids also inhibited the fibrinolytic action of human plasmin on heated and unheated bovine fibrin plates. The greater inhibition noted on heated plates may indicate a primary effect on plasmin rather than on activators of plasmin. The inhibitory effects of N-acetyl neuraminic acid appeared to be potentiated by normal serum inhibitors. Sialic acid did not influence the conversion of fibrin monomer to polymer.N-acetylneuraminic acid may play an important role in preserving the integrity of fibrin deposits in the body.

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3-Phosphonopropionic acids inhibit carboxypeptidase A as multisubstrate analogues or transition-state analogues

Biochemical Journal ◽

10.1042/bj2320015 ◽

1985 ◽

Vol 232 (1) ◽

pp. 15-19 ◽

Cited By ~ 7

Author(s):

D Grobelny ◽

U B Goli ◽

R E Galardy

Keyword(s):

Transition State ◽

Propionic Acid ◽

Phosphonic Acid ◽

Carboxypeptidase A ◽

Phosphonic Acids ◽

Reversible Inhibitors ◽

Transition State Analogues ◽

Structural Analogy ◽

Hydrolysis Of ◽

Methylene Group

A series of phosphonic acid analogues of 2-benzylsuccinate were tested as inhibitors of carboxypeptidase A. The most potent of these, (2RS)-2-benzyl-3-phosphonopropionic acid, had a Ki of 0.22 +/- 0.05 microM, equipotent to (2RS)-2-benzylsuccinate and thus one of the most potent reversible inhibitors known for this enzyme. Lengthening by one methylene group to (2RS)-2-benzyl-4-phosphonobutyric acid increased the Ki to 370 +/- 60 microM. The monoethyl ester (2RS)-2-benzyl-3-(O-ethylphosphono)propionic acid was nearly as potent as (2RS)-2-benzyl-3-phosphonopropionic acid, with a Ki of 0.72 +/- 0.3 microM. The sulphur analogue of the monoethyl ester, 2-ambo-P-ambo-2-benzyl-3-(O-ethylthiophosphono)propionic acid, had a Ki of 2.1 +/- 0.6 microM, nearly as active as (2RS)-2-benzyl-3-(O-ethylphosphono)propionic acid. These phosphonic acids and esters could be considered to be multisubstrate inhibitors of carboxypeptidase A by virtue of their structural analogy with 2-benzylsuccinate. Alternatively, the tetrahedral hybridization at the phosphorus atom suggests that they could be mimicking a tetrahedral transition state for the enzyme-catalysed hydrolysis of substrate.

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Synthesis, protonation equilibrium and peculiar thermal decomposition behavior of cyclo-tri-μ-imidotetraphosphate

Dalton Transactions ◽

10.1039/c4dt00601a ◽

2014 ◽

Vol 43 (30) ◽

pp. 11611-11623 ◽

Cited By ~ 3

Author(s):

Hideshi Maki ◽

Kazuomi Ryousi ◽

Hiroyuki Nariai ◽

Minoru Mizuhata

Keyword(s):

Thermal Decomposition ◽

Propionic Acid ◽

Sodium Salt ◽

Thermal Decomposition Behavior ◽

Protonation Equilibrium ◽

Acidic Conditions ◽

Decomposition Behavior ◽

Hydrolysis Of ◽

Ph Controlled

The synthesis and isolation of the sodium salt ofcyclo-tri-μ-imidotetraphosphate,i.e.Na4cP4O9(NH)3·H2O, were achieved by the hydrolysis of Na4cP4O8(NH)4·2H2O under very weak acidic conditions,i.e.using 0.2 mol L−1propionic acid and the pH-controlled recrystallization procedure.

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Synthesis of [13C3]-B6 Vitamers Labelled at Three Consecutive Positions Starting from [13C3]-Propionic Acid

Molecules ◽

10.3390/molecules23092117 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2117 ◽

Cited By ~ 2

Author(s):

Thomas Bachmann ◽

Michael Rychlik

Keyword(s):

Acid Hydrolysis ◽

Propionic Acid ◽

Potassium Permanganate ◽

Positive Impact ◽

Synthetic Route ◽

Hydrolysis Of

[13C3]-labelled vitamers (PN, PL and PM) of the B6 group were prepared starting from [13C3]-propionic acid. [13C3]-PN was synthesized in ten linear steps with an overall yield of 17%. Hereby, higher alkyl homologues of involved esters showed a positive impact on the reaction outcome of the intermediates in the chosen synthetic route. Oxidation of [13C3]-PN to [13C3]-PL was undertaken using potassium permanganate and methylamine followed by acid hydrolysis of the imine derivative. [13C3]-PM could be prepared from the oxime derivative of [13C3]-PN by hydrogenation with palladium.

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Lipase-catalyzed hydrolysis of 2-(4-hydroxyphenyl)propionic acid ethyl ester to (R)-(−)-2-(4-hydroxyphenyl)propanoic acid

Chemical Papers ◽

10.1007/s11696-019-00796-9 ◽

2019 ◽

Vol 73 (10) ◽

pp. 2461-2468 ◽

Cited By ~ 1

Author(s):

Xin Yuan ◽

Panliang Zhang ◽

Guangyong Liu ◽

Weifeng Xu ◽

Kewen Tang

Keyword(s):

Ethyl Ester ◽

Propionic Acid ◽

Acid Ethyl Ester ◽

Propanoic Acid ◽

Hydrolysis Of

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Limited Hydrolysis of Polysialic Acid by Human Neuraminidase Enzymes

10.26434/chemrxiv.14065025 ◽

2021 ◽

Author(s):

Carmanah D. Hunter ◽

Christopher Cairo

Keyword(s):

Polysialic Acid ◽

Chemical Properties ◽

Sialic Acids ◽

Degree Of Polymerization ◽

Health And Disease ◽

Substrate Tolerance ◽

The Impact ◽

Hydrolysis Of ◽

Unique Chemical

Regulation of sialic acids by human neuraminidase (hNEU) enzymes is important to many biological processes. Defining hNEU substrate tolerance can help to elucidate the roles of these enzymes in regulating sialosides in human health and disease. Polysialic acid (polySia) is a polyanion of α(2→8) linked sialic acids with roles in nervous, reproductive, and immune systems and is dysregulated in some malignancies and mental disorders. The unique chemical properties of this polymer, which include an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its study. Herein we describe the first systematic study of hNEU isoenzyme activity towards polysialic acid in vitro. The experimental design allowed us to study the impact of several factors that may influence polysialic acid degradation including pH, polymer size, and the relative ionic strength of the surrounding media. We report that short chains of polysialic acid (degree of polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not at neutral pH. No hNEU-catalyzed hydrolysis of longer polymers (DP 10-20) was detected. These findings suggest a neuraminidase-independent mechanism for polysialic acid turnover such as internalization and degradation in endosomes and lysosomes.

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DIGESTION BY THE PIG OF THE ENERGY AND NITROGEN IN DRIED, ENSILED AND ORGANIC-ACID-PRESERVED CORN: WITH OBSERVATIONS ON THE STARCH CONTENT OF DIGESTA SAMPLES

Canadian Journal of Animal Science ◽

10.4141/cjas74-051 ◽

1974 ◽

Vol 54 (3) ◽

pp. 377-383 ◽

Cited By ~ 6

Author(s):

H. S. BAYLEY ◽

J. H. G. HOLMES ◽

K. R. STEVENSON

Keyword(s):

Organic Acid ◽

Propionic Acid ◽

Starch Content ◽

Metabolizable Energy ◽

Partial Hydrolysis ◽

Free Glucose ◽

Hydrolysis Of ◽

Balance Trials ◽

Histochemical Examination ◽

Acetic Acids

In the first experiment, three corn–soybean diets were made from either dried, propionic-acid-preserved or naturally ensiled high-moisture corn. In the second experiment, corn was harvested with 23% moisture and prepared for storage either by drying, by treatment with a mixture of propionic and acetic acids, with propionic acid alone or with acetic acid alone; a fifth batch was ensiled. The utilization of energy and nitrogen was measured in balance trials using barrow pigs of 30 kg liveweight. Histochemical examination of the acid-preserved corn indicated partial hydrolysis of the starch molecules, an observation which was supported by the higher levels of free glucose in these samples. The digestible and metabolizable energy values of the diet made with the dried corn were similar in both experiments. In the first experiment, the energy was less available in the propionic-acid-preserved corn than in the dried, but in the second, the energy was more available in that preserved with the organic acids than in the dried. There were no differences in nitrogen utilization between diets in the first experiment, but in the second, the nitrogen was less well utilized in the dried corn diet than in those containing the organic-acid-preserved corn. Examination of the α-linked polysaccharides in the digesta showed that they had been incompletely digested in the diet containing the dried corn in experiment 2.

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