Aminotransferases and Transaminations

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Questions and Answers

What is the primary factor that determines the half-life of a cytosolic protein?

The protein's molecular weight

The amino-terminal residue (correct)

The protein's subcellular localization

The presence of PEST sequences

What is the function of E3 enzymes in protein degradation?

To hydrolyze peptide bonds

To read N-terminal residues (correct)

To regulate proteasome activity

To synthesize ubiquitin

What is the role of the human papilloma virus (HPV) in protein degradation?

It inhibits E3 enzymes

It deubiquitinates proteins

It activates a specific E3 enzyme (correct)

It regulates proteasome activity

What is the function of the proteasome in protein degradation?

To hydrolyze peptide bonds Signup and view all the answers

What is the effect of an N-terminal arginine residue on protein half-life?

It decreases protein half-life Signup and view all the answers

What is the function of PEST sequences in protein degradation?

They mark proteins for degradation Signup and view all the answers

What is the composition of the 20S proteasome?

2 copies of 14 subunits Signup and view all the answers

What is the energy requirement for proteasome activity?

ATP Signup and view all the answers

What is the role of aminotransferases in amino acid metabolism?

To catalyse the transfer of an α-amino group from an α-amino acid to an α-ketoacid Signup and view all the answers

What is the product of the transamination reaction catalysed by aspartate aminotransferase (AST)?

Oxaloacetate and glutamate Signup and view all the answers

What is the function of glutamate dehydrogenase in amino acid metabolism?

To catalyse the oxidative deamination of glutamate to produce ammonia Signup and view all the answers

What is the direction of the glutamate dehydrogenase reaction in vivo?

Favours ammonia formation Signup and view all the answers

What is the role of alanine aminotransferase (ALT) in amino acid metabolism?

To catalyse the transfer of an amino group from alanine to α-ketoglutarate Signup and view all the answers

What is the significance of the allosteric regulation of glutamate dehydrogenase in vertebrates?

It allows for the regulation of ammonia levels in the body Signup and view all the answers

What is the subunit structure of glutamate dehydrogenase?

A hexamer of six identical subunits Signup and view all the answers

What is the fate of ammonia in most terrestrial vertebrates?

It is converted into urea and excreted Signup and view all the answers

What is the primary fate of amino acids in mammals if they are not utilized for protein biosynthesis?

They are degraded in the liver. Signup and view all the answers

What is the role of protein degradation in regulating cellular functions?

It regulates various functions, including gene transcription, cell-cycle progression, and organ formation. Signup and view all the answers

What is the outcome of the degradation of I-κB in response to inflammatory signals?

NF-κB is activated and transcribes target genes. Signup and view all the answers

What is the first step in the degradation of amino acids in the liver?

Deamination to form α-ketoacids. Signup and view all the answers

What is the role of E3 in the degradation of I-κB?

It ubiquitinates I-κB. Signup and view all the answers

What is the outcome of the phosphorylation of I-κB at two serine residues?

An E3 binding site is created, leading to the degradation of I-κB. Signup and view all the answers

What is the role of the NF-κB-I-κB system in the regulation of the inflammatory response?

It illustrates the interplay of several key regulatory motifs, including receptor-mediated signal transduction, phosphorylation, and controlled degradation. Signup and view all the answers

What is the fate of the carbon skeletons of α-ketoacids in the liver?

They enter the metabolic mainstream as precursors for gluconeogenesis or citric acid cycle intermediates. Signup and view all the answers

Study Notes

Protein Degradation

The half-life of a cytosolic protein is determined by its amino-terminal residue, known as the N-terminal rule.
A yeast protein with methionine at its N terminus has a half-life of more than 20 hours, whereas one with arginine at this position has a half-life of about 2 minutes.
E3 enzymes are the readers of N-terminal residues, and they favor rapid ubiquitination if the residue is destabilizing (e.g., arginine or leucine) and do not favor ubiquitination if the residue is stabilizing (e.g., methionine or proline).
Other signals that identify proteins for degradation include cyclin destruction boxes and PEST sequences.

Human Papilloma Virus (HPV)

HPV encodes a protein that activates a specific E3 enzyme, which ubiquitinates the tumour suppressor p53 and other proteins that control DNA repair, leading to their destruction.
The activation of this E3 enzyme is observed in more than 90% of cervical carcinomas.

Proteasome

The proteasome is the protein that executes proteolysis, using the energy of ATP to hydrolyze peptide bonds.
The proteasome has a sedimentation coefficient of 26S and is composed of 2 subunits: a 20S proteasome and a 19S regulatory subunit.
The 20S complex contains 2 copies of 14 subunits and has a mass of 700 kD.

Transaminations

Aminotransferases catalyze the transfer of an α-amino group from an α-amino acid to an α-ketoacid.
The α-amino group of many amino acids is transferred to α-ketoglutarate to form glutamate.
Glutamate can transfer the amino group to oxaloacetate to form aspartate or glutamine can undergo oxidative deamination to produce α-ketoglutarate and ammonia.

Aspartate Aminotransferase (AST)

AST catalyzes the transfer of an amino group from aspartate to α-ketoglutarate to form oxaloacetate and glutamate.
This transamination reaction is reversible.

Alanine Aminotransferase (ALT)

ALT catalyzes the transfer of an amino group from alanine to α-ketoglutarate to form pyruvate and glutamate.

Glutamate Dehydrogenase

Glutamate dehydrogenase catalyzes the conversion of glutamate to α-ketoglutarate and ammonia.
The enzyme can use NAD+ or NADP+ as the oxidizing agent.
The oxidation produces α-iminoglutarate, which is hydrolyzed to form ammonia and α-ketoglutarate.

Regulation of Protein Degradation

The degradation of proteins regulates a number of functions, including gene transcription, cell-cycle progression, organ formation, circadian rhythm, inflammatory response, tumor suppression, cholesterol metabolism, and antigen processing.
The degradation of proteins is dynamically controlled by altering the stability and abundance of regulatory proteins.
For example, the control of the inflammatory response is regulated by the degradation of an inhibitory protein, I-kB, which allows the transcription factor NF-κB to stimulate transcription of target genes.

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Description

Learn about aminotransferases, also known as transaminases, and how they facilitate the transfer of alpha-amino groups from amino acids to alpha-ketoacids. Understand the role of glutamate and oxidative deamination in this process.