Lecture 28: Nitrogen Metabolism 1 Flashcards
Protein breakdown and the Urea cycle
1) Where are amino acids stored in the body?
2) What three ways are amino acids obtained?
1) There is NO STORE for amino acids in the body, they must be obtained
2)
- diet
- de novo synthesis
- recovered from protein degradation
What is an a-keto acid?
The carbon skeleton of an amino acid without the alpha amino goup
Which amino acids can be synthesised?
non-essential amino acids
What supplies the amino acid pool?
- amino acids from degraded body proteins
- amino acids from dietary proteins
- synthesis of non-essential amino acids from simple intermediates
What is the amino acid pool depleted by?
- protein synthesis
- nitrogen containing molecule precursors
- conversion to glucose, glycogen, fatty acids, ketone bodies etc.
What is the most important way of obtaining nitrogen in humans?
the diet
1) What is protein turnover?
2) How does this system function in healthy adults?
1) most proteins are continually being synthesised or degraded
2) rate of synthesis matches the rate of degradation, keeping total amount of protein present constant. 300-400g of protein hydrolysed and resynthesised each day
How are proteins degraded inside cells?
- ATP-dependent ubiquitin-ptoteasome system
- ATP-independent enzyme system of the lysosomes
Describe the ubiquitin-proteasome proteolytic pathway
- Step 1: Protein selected for degradation is tagged with molecules of ubiquitin, using ATP
- Step 2: Tagged proteins recognised by cytosolic proteosome
- Step 3: proteosome unfolds, deubiquitinates, and transports the protein to its proteolytic core, using ATP
- Step 4: peptide produced are degraded to amino acids to enter the amino acid pool
- Step 5: ubiquitin recycled to mark another protein for degradation.
How does ubiquitination occur for protein degradation?
linkage of a-carboxyl group c-terminal glycine to e-amino group of lysine, using ATP and enzyme catalysis
How is degradation of proteins determined?
by structural properties, such as :
- oxidation levels
- N-terminal residue
- PEST sequences
The stomachs role in digestion
- hydrochloric acid denatures proteins (pH 2.5)
- pepsin- an acids stable endopeptidse which releases aas and peptides
- mechanical digestion
In what form is pepsin created?
an inactive zymogen
How is pepsin activated?
by HCl or auto-catalytically
Why does the pancreas release many different proteases?
- varying specificity for different amino acid R-groups
- eg. trypsin only cleaves at an arginine or lysine
How does trypsin trigger the enzyme cascade?
- trypsin activated
- acts auto-catalytically to increase trypsin production
- trypsin also acts to increase activation of other proteases
What do aminopeptidases (exopeptidases) do?
Cleave N-terminal residues to produce smaller peptides and free amino acids
How are free amino acids absorbed in digestion?
- Absorbed by enterocytes
- using Na+ co-transporter (secondary) system
How are di/tri peptides absorbed in digestion?
- absorbed by enterocytes
- using H+ transport system
- hydrolysed to amino acids in cytosol
Where do amino acids go after being absorbed?
- released into portal system (hepatic-portal vein) by facilitated diffusion
- metabolised by liver
- OR released into circulation
