Week 4 Flashcards
What two amino acids are both glucogenic and ketogenic?
- threonine
- tyrosine
Is there a net loss of nitrogen?
There is not net loss of nitrogen, synthesis = degradation
What are the 3 different metabolic circumstances in which amino acid catabolism occurs?
- normal synthesis and degradation of cellular proteins. those not recycles are oxidised to yield ATP
- Dietary protein surplus is catabolised and oxidised to yield ATP
- during starvation or in uncontrolled diabetes mellitus, carbohydrates are either unavailable or not properly used, cellular proteins will be oxidised to yield ATP
What proportion of dietary protein is endogenous?
half
What types of amino acids are sent to the muscles?
Branched-chain amino acids
What is the summary of dietary protein breakdown?
- lots of proteases, beginning in the stomach followed by the absorption of free amino acids and transport to the liver (except branched chain AA that go to the muscle)
What do trypsin and chymotrypsin do in the small intestine?
They cut proteins and larger peptides into smaller peptides.
What do aminopeptidases and carboxypeptidases A and B do in the small intestine?
Degrade peptides into amino acids
Cleavage of dietary protein by proteases secreted from the pancreas starts by?
Enteropeptidase starts the activation by converting trypsinogen to trypsin
The release and activation of pancreatic zymogens is mediated by which hormones?
Cholecystokinin and secretin
How do neutral amino acids transport?
Across a concentration gradient - glucose transporters (GLUT)
How do basic amino acids transport?
Charge dependent transporters - cotransport
How do acidic amino acids transport?
Transported with sodium ions
What is Hartnup disease? (autosomal recessive metabolic disorder)
- neurologic
- diarrhoea
- red scaly skin rash when skin is exposed to sunlight
This is where a person cannot absorb amino acids properly from the intestine and cannot reabsorb them properly from tubules in teh kidneys, particularly tryptophan
How is Hartnup diease tested?
A urine test that checks for high levels of neutral amino acids
SLC6A19 gene
What does the premature activation of trypsinogen lead to?
Results in the activation of trypsin and many other enzymes because trypsin is an activator for many proenzymes
What can the premature activation of trypsinogen lead to?
- pancreatic autodigestion
- detected by increased pancreatic amylase in serum
What are some of the causes of trypsin and pancreatic autodigestion?
- mutations within trypsinogen
- mutations within normal trypsin inhibitor
- clogged ducts, by gall stones.
What two amino acids make up gluten?
Gliadin and glutenin
What are some of the symptoms of cystinuria?
- kidney stones that can block the urinary tract from unabsorbed cysteine
How are most non-selective proteins degraded?
In the lysosomes, entry by macroautophagy that is the enclosure of a volume of the cytoplasm by an intracellular membrane
Where are all proteins synthesised?
In the cytosol. They are synthesised on ribosomes attached to the ER
Where is mRNA synthesised?
In the nucelus
What are the 2 main pathways in which eukaryotic cellular proteins are degraded?
- ATP independent process - degrades proteins inside of lysosomes.
- ATP dependent pathway - targets specific proteins for degradation in proteosomes if they are attached to another protein, ubiquitin
What are the 4 digestive processes mediated by the lysosome?
- endocytosis
- pinocytosis
- phagocytosis
- autophagy
How are short lived regulatory proteins degraded? and where
Degraded in the cytosol by the ubiquitin system
What is the ubiquitin-mediated degradation of amino acids?
It is the selective labelling of targetting proteins by ubiquitin molecules. Ubiquitin is a 76AA and binds covalently to available lysine residues on target proteins which are then recognised by proteases
Describe ubiquitination?
Once one ubiquitin molecule joins, multiple join yielding a poly-ubiquitin chain
Some are modified, called multi-ubiquitination
How many ubiquitin molecules must be attached to the lysine residues on the condemned protein in order for it to be recognised by the 26S?
4 molecules
What is the role of E1 subunit in ubiquitin-protein degradation?
Activation protein by cysteine on E1
What is the role of E2 in ubiquitin degradation?
Conjugation protein
What is the role of E3 in Ubiquitin degradation?
Ubiquitin ligase - substrate recognition
What is another example of proteolytic systems in cells?
Apoptosis
What is the role of apoptosis?
- eliminates unwanted or non-functional cells
- involves activation of caspases
- caspases have a cysteine at their active site and cleave target proteins at specific aspartic acids
Is there advantage in the inhibition of protein degradation?
- inhibition of proteosome in mammalian cells - induces apoptosis and sensitises cells to pro-apoptotic agents
- chemotherapy
What is an example of a proteosomal inhibitor used in chemotherapy?
Velcade, which is effective against multiple myeloma
What is Liddle Syndrome?
A mutation in the subunit of the renal epithelial NA+ channel interferes with the binding of an E3 ligase that mediates its degradation. Channel accumulation leads to Na2+ reabsorption in excess and severe hypertension.
What are 3 disorders with defects in cellular protein degradation regarding the E3 subunit of ubiquitin?
Liddle Syndrome
Juvenile parkinsonism
Breast and ovarian cancer
HPV induced cervical cancer
