scholarly journals Thiamine Derivatives of Disulfide Type. V. Kinetic Studies of the Reaction between Thiamine Propyl Disulfide or Homologes and L-Cysteine

1967 ◽  
Vol 15 (5) ◽  
pp. 693-700 ◽  
Author(s):  
Hisashi Nogami ◽  
Jun Hasegawa ◽  
Noriko Ikari
Keyword(s):  
Kinetic Studies ◽  
Type V ◽  
Derivatives Of

scholarly journals The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5980
Author(s):  
Ajda Taler-Verčič ◽  
Marko Goličnik ◽  
Aljoša Bavec
Keyword(s):  
Catalytic Mechanism ◽  
Kinetic Studies ◽  
Amino Acid Sequences ◽  
Site Directed Mutagenesis ◽  
Paraoxonase 1 ◽  
Homocysteine Thiolactone ◽  
Substrate Promiscuity ◽  
Serum Paraoxonase ◽  
And Function ◽  
Derivatives Of

Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid—bioactive δ-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1. However, there is still a whole world of mystery waiting to be discovered, which would elucidate the substrate promiscuity of a group of enzymes that are so similar in their evolution and sequence yet so distinct in their function.

Inhibition of UDP-glucuronosyltransferase by 5'-O-amino Acid and Oligopeptide Derivatives of Uridine: Structure-Activity Relationships

1998 ◽  
Vol 53 (3-4) ◽  
pp. 173-181 ◽  
Author(s):  
Zlatina G. Naydenova ◽  
Konstantin C. Grancharov ◽  
Dimitar K. Alargov ◽  
Evgeny V. Golovinsky ◽  
Ivanka M. Stanoeva ◽  
...  
Keyword(s):  
Amino Acid ◽  
Kinetic Studies ◽  
Quantitative Structure Activity Relationship ◽  
Inhibitory Effect ◽  
Minimum Length ◽  
Qsar Study ◽  
Qsar Analysis ◽  
Structure Activity ◽  
Udp Glucuronosyltransferase ◽  
Derivatives Of

Abstract The inhibitory effect of a series of 5′-O-amino acid and oligopeptide derivatives of uridine on rat liver UDP-glucuronosyltransferase (UGT) activities was investigated using two assay systems. A quantitative structure-activity relationship (QSAR) study was performed. The compounds include a lipophilic residue linked to the nucleoside by a variable spacer. More­ over, half of the derivatives have two spacers linked to the uridine moiety. Compound 1, a serine derivative of isopropylideneuridine, was found to be the most potent inhibitor of both 4-nitrophenol (4-NP) and phenolphthalein (PPh) glucuronidation, with an I50 of 0.45 mᴍ and 0.22 mᴍ , respectively. Kinetic studies with this substance revealed a mixed type of inhibition towards 4-NP and UDP-glucuronic acid, with apparent Ki values of 150 μᴍ and 120 μᴍ , respectively. The dipeptide derivatives 11-14 exhibited a low activity against 4-NP conjuga­ tion. However, a marked suppression of PPh glucuronidation was found with compounds 11 and 13. Generally, compounds with two spacers are more inhibitory against the UGT activi­ties studied. The QSAR analysis outlined the significance of the spacers with a minimum length of 5 atoms and lipophilic residues linked to them for the inhibitory effect of the compounds. The most significant contribution to this effect is given by the six-atom spacer for both, 4-NP and PPh substrates. 4-NP converting UGT isoforms seem to respond more specifically to the inhibitors: a five-atom for the first and a six-atom for the second spacer enhance binding to both 4-NP and PPh conjugating isoenzymes, while a long second spacer contributes to inhibitor binding to UGT isoforms only converting PPh.

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