Related Experiment Video
Updated: Jul 19, 2026
12:07
Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Summary
Nicotinamide methyltransferase enzyme activity was inhibited by S-Adenosylethionine and S-adenosylhomocysteine. This competitive inhibition may affect liver nicotinamide levels and N1-methylnicotinamide excretion.
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Nicotinamide methyltransferase (NMT) is a key enzyme in nicotinamide metabolism.
- Understanding NMT regulation is crucial for metabolic studies.
- Inhibitors of NMT can provide insights into its function.
Purpose of the Study:
- To investigate the inhibitory effects of S-Adenosylethionine and S-adenosylhomocysteine on nicotinamide methyltransferase.
- To characterize the type of inhibition exerted by these compounds.
Main Methods:
- Development of an assay utilizing an Affi-Gel 601 boronate column for substrate-product separation.
- Enzyme inhibition studies with varying concentrations of S-Adenosylethionine and S-adenosylhomocysteine.
- Analysis of substrate concentration curves to determine inhibition kinetics.
Main Results:
- Both S-Adenosylethionine and S-adenosylhomocysteine demonstrated dose-dependent inhibition of NMT.
- S-Adenosylethionine was a less potent inhibitor than S-adenosylhomocysteine, requiring five times higher concentration for 50% inhibition.
- Kinetic analysis indicated a competitive inhibition pattern for both compounds.
Conclusions:
- S-Adenosylethionine and S-adenosylhomocysteine competitively inhibit nicotinamide methyltransferase.
- This inhibition has the potential to alter hepatic nicotinamide levels.
- Changes in liver nicotinamide may consequently affect urinary N1-methylnicotinamide excretion.
Related Concept Videos
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
01:25Adrenergic Agonists: Indirect-Acting Agents
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
01:29Drugs Affecting Neurotransmitter Synthesis
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
01:17Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
01:28Biosynthesis of Nucleic Acids
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...