W6 - Protein Metabolism Flashcards
What are proteins metabolised to in the stomach?
Polypeptides
Where do the polypeptides from the stomach travel to?
Small intestine
–where peptidases (secreted from the pancreas + intestinal wall) break them down to:
- aa, di peptidases + tri peptidases.
What happens to the aa in the small intestine?
Absorbed into blood
aa after eating - fed state
⬆️ insulin in blood
aa arrive at liver from the hepatic portal vein
aa after eating - fed state
What do the aa do once arrived at the liver
Used for protein synthesis
Transported to other tissues
Storage - TAG / Glycogen
aa when not having eaten for a while - fasted state
Body needs to make energy
aa broken down as body is in a catabolic state
Glucagon in blood
What are the 2 ways aa can be classified?
Glucogenic
Ketogenic
Fate of ketogenic aa
Will be converted to AcetylCoA or Acetoacetyl CoA
Then enter TCA cycle if in catabolic situation
OR
Converted back to be stored as fat.
Fate of glucogenic aa
Feed into TCA cycle:
- Used for energy if in catabolic state.
OR
- If taken in excess aa, store them as CHO
Difference between aa + a-keto acid
a-keto acid is an aa but with the N group removed
What happens to the aa that aren’t used for protein synthesis or synthesis of any N containing compounds?
Metabolised by transamination or deamination
What is the most common way to remove N from an aa?
By transaminating it
How does transamination work/.
N group on aa is transferred to an a-keto acid
= Interchangeable reaction
How is deamination carried out?
W/ dehydrogenase
What does deamination result in?
a-keto acid
NH3
What is transamination important for?
Production of non-essential aa
Transaminases are freely reversible but what do they depend on?
Substrate availability
Where does transamination occur?
Most tissues including the muscle
What do main transamination reactions involve?
Alanine
Aspartate
Glutamate
What does the liver do during exercise in regards to alanine?
Increases its uptake by about 50%
Why does the liver increase the uptake of alanine during exercise?
As it can be converted to pyruvate.
- Pyruvate can go through gluconeogenesis OR can be oxidised to give energy
Why is aspartate important for nitrogen excretion?
Plays a part in the urea cycle
When can transamination be heavily utilised?
During periods of starvation or prolonged exercise
Where does oxidative deamination occur?
Mit matrix of liver
What happens when there’s a shortage of substrates during oxidative deamination in the liver?
Glutamate is broken down to give:
- NADH (can enter ETC)
- a-ketoglutarate (can enter TCA cycle)
Which aa is the only aa to contain 2 nitrogens?
Glutamine
What can be used to make glutamine?
How?
Glutamate
Glutamate + NH4 + ATP –> Glutamine + ADP
Which aa is the most abundant free aa in the skeletal muscle + blood?
Glutamine
What is glutamine really important for?
Ammonia transport
Gluconeogenic precursor
Helps transfer C + N between skeletal muscle + kidneys
Fuel for GI tract + immune system
What is meant by glutamine being a gluconeogenic precursor?
If amino group is lost from glutamine = glutamate
If another is lost = a-ketoglutarate (can enter TCA cycle)
Then can go round + back up through gluconeogensis OR can be used for oxidation.
Example of a cataplerotic loss
Losing glutamine from muscles
Where does the urea cycle happen?
Liver
UREA CYCLE - STEP 1 (Before actually entering cycle)
NH3 + CO2 + 2ATP—>
By what enzyme?
Carbamoyl P + 2ADP
By Carbamoyl P synthetase
IRREVERSIBLE
What is carbamoyl P synthetase stimulated by?
N-acetylglutamate
How does carbamoyl P enter the urea cycle?
By combining w/ L-ornithine –> citrulline
UREA CYCLE
Citrulline –> L-argininosuccinate
Citrulline + ATP + N from aspartate–> L-argininosuccinate + AMP
UREA CYCLE
What happens to the fumarate produced between L-argininosuccinate –> L-arginine
Leaves + enters TCA cycle
In which part of the urea cycle is urea released into the blood?
Between L-arginine + L-ornithine
What must happen to get the a-keto acid from BCAAs
Must be transaminated w/ a-ketoglutarate to get glutamate + the a-ketoacids of BCAAs
Enzyme = BCAT
What happens to the glutamate produced from BCAA oxidation?
Transaminates to form alanine
Alanine leaves muscle + taken up by liver
What then happens to the a-ketoacids of BCAAs?
Undergo dehydrogenation by BCKDH
Where H group is removed so they have their own specific dehydrogenase.
What does valine make after the BCAA oxidation?
Succinyl CoA
- Glucogenic aa
What does isoleucine make after the BCAA oxidation?
Succinyl CoA
- Glucogenic aa
Also creates acetyl-CoA
- Ketogenic
What does leucine make after the BCAA oxidation?
Acetyl CoA + Acetoacetyl CoA
- Ketogenic
Where does glycogenolysis occur?
Muscle
What does glycogenolysis result in?
G-6-P which can go further through glycolysis to create pyruvate.
Glucose-Alanine cycle
Pyruvate created from G-6-P in glycogenolysis. What can happen to it?
Can transaminate w/ an aa to form Alanine in the muscle.
Released into blood.
Taken up by liver
Undergoes transamination w/ a-ketoglutarate –> glutamate + pyruvate.
What can happen with the pyruvate formed from the glucose-alanine cycle when in the liver?
Can go through gluconeogenesis.
Glucose can be released back into blood + transported to wherever needed.
Glucose alanine cycle
What happens to the glutamate in the liver?
Deaminated
NH3 lost through urea OR used to make plasma proteins.
How is net protein balance calculated?
Protein synthesis - Protein breakdown
Transcription
How is it controlled?
By:
Transcription factors
Coactivator proteins
Repressors
Transcription
How is it controlled?
What comes under transcription factors?
Activators
Enhancer sites
Transcription
How is it controlled?
What comes under coactivator proteins?
Signals
Transcription
How is it controlled?
What comes under repressors?
Silencer
Role of tRNA
Brings aa to mRNA
What catalyses the binding of aa to the appropriate tRNA
Aminoacyl tRNA synthetase
3 stages of translation
Initiation
Elongation
Termination
What does the process of initiation of translation involve?
40s + 60s ribosomal units
mRNA mol
Initial aminoacyl-tRNA (tRNA mol w/ methionine attached)
Protein factors to control initiation process
Energy from GTP
Examples of the protein factors to control the initiation process of translation
p70s6 kinase
What does elongation in translation involve?
Addition of aa to carboxyl terminal end of polypeptide chain
Why does elongation in translation occur?
Anticodon of aminoacyl-tRNA recognises 2nd codon on mRNA
Elongation in translation
Where does the peptide bond occur?
Between carboxyl group of MET + 2nd aa (still attached to tRNA)
Termination in translation
What does the termination / release factor do?
Releases the complete polypeptide chain from the last tRNA
80s dissociates to its 2 x 40s + 60s subunits.
Post-translational control of protein function
What is it regulated by?
- Chaperones
- Scaffolding proteins
What are the 5 main pathways in which protein can be broken down?
Ubiquitin-proteosome
Lysosomal proteolysis
Caspases
Matrix metalloproteases
Calpain
How can muscle protein synthesis + breakdown be measured?
By looking at:
Fractional synthetic rate (FSR)
OR
Fractional breakdown rate (FBR)
How is fractional synthetic rate typically measured?
Biopsies and Isotopes
At rest what is greater? - Muscle protein synthesis or muscle protein breakdown
Muscle protein breakdown
When taking a muscle biopsy, what muscle protein fractions do you separate out?
Collagen
Myofibrillar proteins
Mitochondria proteins
Sarcoplasmic proteins
Which of the muscle proteins is more associated with resistance type exercise?
Myofibrillar proteins
Which of the muscle proteins is more associated with endurance type exercise?
Mitochondrial proteins
What does exercise do to net muscle protein balance?
Improves it but still no positive values are reached.
Availability of substrates in the human body.
Where can the CHO be?
Plasma glucose
Liver glycogen
Muscle glycogen
Availability of substrates in the human body.
Where can the fats be?
Plasma FAs
Plasma TAGs
Muscle TAGs
Adipose tissue
How does the VO2 max test step protocol work in the fat max test?
Start at low intensity at 60W on a bike.
⬆️W by 35 every 3 mins.
When collecting data for the VO2 max test step protocol in the fat max test, which data do you collect and disregard?
Disregard = 1st min of each workload
Calculate = Average of final 2 mins
Where can BCAA be oxidised?
Kidneys + muscle
What happens to net balance following resistance exercise ONLY
⬆️ but remains -ive
When BCAAs are oxidised, what is their N group generally used to form?
Glutamate + then alanine
Where does the decarboxylation of a-ketoacids involving branched chain a-keto acid dehydrogenase occur?
In the mit
Which protein breakdown system is most likely to be used in the muscle following exercise?
Calpain system
Which amino acid is always the first in a polypeptide chain?
Methionine
