Related Experiment Video
Updated: Jan 18, 2026
07:37
Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening
Published on: May 13, 2020
2.3K
Arylalkylamine N-acetyltransferase: "the Timezyme".
1Section on Neuroendocrinology, Office of Scientific Director, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. kleind@mail.nih.gov
The Journal of Biological Chemistry
|December 14, 2006
Summary
Arylalkylamine N-acetyltransferase regulates daily melatonin production and biological timing in vertebrates. Its activity is controlled by cyclic AMP-dependent phosphorylation, forming a complex that activates the enzyme and prevents degradation.
Area of Science:
- Biochemistry
- Chronobiology
- Neuroscience
Background:
- Arylalkylamine N-acetyltransferase (AA-NAT) is crucial for melatonin synthesis in the pineal gland, regulating vertebrate biological timing.
- AA-NAT is also present in the retina, suggesting roles beyond melatonin production, potentially in neurotransmission and detoxification.
Purpose of the Study:
- To elucidate the regulatory mechanisms controlling Arylalkylamine N-acetyltransferase activity.
- To understand the role of post-translational modifications and protein interactions in AA-NAT function.
Main Methods:
- Investigated the role of cyclic 3',5'-adenosine monophosphate (cAMP)-dependent phosphorylation in AA-NAT activity.
- Examined the interaction of phosphorylated AA-NAT with 14-3-3 proteins.
- Assessed the impact of this complex formation on enzyme activity and proteasomal degradation.
Main Results:
- Cyclic AMP-dependent phosphorylation significantly increases AA-NAT activity.
- Phosphorylation facilitates the formation of a regulatory complex between AA-NAT and 14-3-3 proteins.
- This complex formation activates the enzyme and protects it from proteasomal proteolysis.
Conclusions:
- AA-NAT regulation involves a conserved mechanism of cAMP-dependent phosphorylation and 14-3-3 protein interaction.
- This regulatory system is influenced by circadian rhythms and environmental light cues.
- Understanding AA-NAT regulation provides insights into biological timing and potential therapeutic targets.
Related Concept Videos
01:24Phase II Reactions: Acetylation Reactions
761
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
761
01:30Preparation of Amines: Alkylation of Ammonia and Amines
4.6K
Alkylation is one of the methods used to prepare amines. Direct alkylation of ammonia or a primary amine with an alkyl halide gives polyalkylated amines along with a quaternary ammonium salt through successive SN2 reactions. This process of making the quaternary salt through the direct alkylation method is called exhaustive alkylation.
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
4.6K
01:19Allosteric Proteins-ATCase
6.5K
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...
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...
6.5K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
2.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.5K
01:19Amines to Amides: Acylation of Amines
3.4K
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
3.4K
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
3.7K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
3.7K