Related Experiment Video
Updated: Jul 18, 2026
11:17
Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor
Published on: February 10, 2014
An unprecedented twist to ODCase catalytic activity
Masahiro Fujihashi1, Angelica M Bello, Ewa Poduch
1Molecular Design and Information Technology Center, Leslie Dan Faculty of Pharmacy, Toronto, ON M5S 2S2 Canada.
Journal of the American Chemical Society
|October 27, 2005
Summary
Orotidine-5'-monophosphate decarboxylase (ODCase) typically uses a carbanion mechanism. However, it can convert 6-cyano-uridine-5'-monophosphate to barbiturate-5'-monophosphate, suggesting an electrophilic mechanism for novel inhibitor design.
Area of Science:
- Biochemistry
- Enzymology
- Medicinal Chemistry
Background:
- Orotidine-5 -monophosphate decarboxylase (ODCase) is a key enzyme in pyrimidine biosynthesis.
- ODCase typically catalyzes decarboxylation via a carbanion intermediate at the C6 position.
Purpose of the Study:
- To investigate the reaction mechanism of ODCase with 6-cyano-uridine-5 -monophosphate.
- To explore the potential of ODCase in novel inhibitor design.
Main Methods:
- Biochemical assays to study the conversion of 6-cyano-uridine-5 -monophosphate by ODCase.
- Analysis of the reaction products, including barbiturate-5 -monophosphate.
Main Results:
- ODCase converts 6-cyano-uridine-5 -monophosphate to barbiturate-5 -monophosphate.
- This conversion suggests an unusual pathway involving an electrophilic center at the C6 position, distinct from the typical carbanion mechanism.
Conclusions:
- ODCase exhibits an unexpected reactivity profile with cyano-substituted uridine monophosphates.
- This unique biochemical pathway offers a novel strategy for designing ODCase inhibitors.
Related Concept Videos
01:46Oxidative Cleavage of Alkenes: Ozonolysis
In ozonolysis, ozone is used to cleave a carbon–carbon double bond to form aldehydes and ketones, or carboxylic acids, depending on the work-up.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:27Inductive Effects on Chemical Shift: Overview
The protons in unsubstituted alkanes are strongly shielded with chemical shifts below 1.8 ppm. Methine, methylene, and methyl protons appear at approximately 1.7, 1.2 and 0.7 ppm, while the proton signal from methane appears at 0.23 ppm. An electronegative substituent, such as chlorine, withdraws the electron density from the protons, increasing their chemical shift. Progressive substitution of the hydrogens in methane by chlorine shifts the proton signals increasingly downfield, to 3.05 ppm in...
01:20¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)
When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
01:26Photochemical Electrocyclic Reactions: Stereochemistry
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
01:31Dielectric Polarization in a Capacitor
The presence of a dielectric medium in a capacitor not only changes the voltage and capacitance but also affects the electric field. In general, dielectrics can be of two types: polar and nonpolar. In a polar dielectric, the positive and negative charges in the molecules are separated by a distance and hence have a permanent dipole moment. In contrast, no such charge separation exists in a nonpolar dielectric, however the nonpolar molecules get polarized in the presence of an external electric...