Nitrogen Sources and Amino Acid Metabolism Flashcards
How is the amino acid pool maintained?
By digestion of dietary protein, turnover of cellular and tissue protein, and synthesis of non-essential amino acids
What is Pyridoxal phosphate?
Derived from Vitamin B6, coenzyme that is covalently bound to aminotransferases and is required for the transamination mechanism
How does the ubiquitin-proteasome pathway work?
Pathway is cytosolic and depends on covalent attachment of ubiquitin to lysine residues of a protein that has been targeted for degradation.
The polyubiquitylated protein will be recognized by the proteasome complex and is degraded to smaller peptides in an ATP dependent process.
How is the lysosomal pathway different from the ubiquitin-proteasome pathway?
Lysosomal degradation pathway is responsible for degradation of bulk cellular proteins and organelles (mitochondria)
How does the lysosomal degradation pathway work? What is autophagy?
Autophagy= when cytosolic material is captured into membrane bound compartments called autophagsomes.
- Autophagosomes will fuse with lysosomes/vacuoles where proteases and lipases degrade the sequestered material.
How does Insulin influence the lysosomal degradation pathway?
Insulin levels after a meal inhibit autophagy by activating the MTORC1 kinase through activity of Akt. This causes a decrease in autophagy.
What happens to the lysosomal degradation pathway during starvation?
During starvation and amino acid deprivation, signaling turns of MTORC1 kinase, which strongly induces the autophagy pathway to degrade proteins and maintain the amino acid pools
When one is under starvation and amino acid deprivation how is translation inhibited?
Occurs due to phosphorylation and sequestration of the initiation factor, elF2.
What happens when you have insulin and increased amounts of amino acids?
This causes phosphorylation of 4E-BP1 through MTORC1 which triggers release of elF4. Active MTORC1 also increases phosphorylation of elf4B which enhances helices activity to increase translation
What do Aminotransferases do? And where do transamination reactions typically occur?
Most occur in the liver and muscle (muscle during starvation). They remove the amino group from the amino acid to an alpha-leto acid.
Example: Alanine amino transferase
alanine + aKG –> Pyruvate + Glutamate
What does Pyridoxal phosphate do?
It transfers the amino group of an amino acid to the coenzyme to generate a pyridoxamine phosphate intermediate. This intermediate will then react with an alpha-keto acid to form an amino acid
What does Glutamate dehydrogenase do? What regulates it?
Deamination reaction that converts glutamate to aKG and ammonia (NH3).
Concentrations of glutamate, aKG and ammonia regulate it. If glutamate levels are high (protein reach meal), Glutamate dehydrogenase will be activated for deamination.
REVERSIBLE REACTION. Works in both ways!
What is Alkaptonuria?
Deficiency in homogentisate oxidase pathway, in pathway for degradation of tyrosine. Causes homogentisate to accumulate
What is Maple syrup urine disease (MSUD)?
Deficiency in a-KG dehydrogenase; causes lots of amino acids to accumulate
What is homocystinuria?
Deficiency in cystathionine synthase, causes homocystine to be elevated
