🐟 Breakdown + Urea Formation Flashcards
Growth equation?
growth = synthesis - breakdown
What’s positive nitrogen balance?
protein/AA retained exceeds amount that’s broken down + excreted because:
-more of the AAs in the AA pool being converted into body protein + less body protein broken down or excreted
What’s negative nitrogen balance?
protein input is superseded by breakdown
Fate of ingested protein?
Broken down -> AAs to make new protein eg muscle fibres, enzymes (structural or functional)
-Proteins broken down, in nitrogen balance so breakdown = synthesis
Input is 100g a day + output 100g a day.
Where is nitrogen removed?
in liver via formation of urea
Causes of positive nitrogen balance?
- Growth in small children
- Pregnancy as they take in + lay down more protein
- Exercise, tissue hypertrophy due to anabolic hormones
Cause of negative nitrogen balance?
protein deficiency
What’s negative N balance associated with + eg?
pathophysiology rather than physiology
eg wasting diseases, burns, trauma, response to catabolic hormones, or lack of anabolic ones (eg in diabetes) –> lose body protein mass
How protein metabolism deals with AA?
- dealing with C skeleton + N
- breaking down of protein via peptidases —> constituent AAs
What’s C skeleton used for?
for energy metabolism or biosynthesis
Effect of N in body?
toxic (adverse effect on neuronal cells)
What happens if can’t produce urea?
die in infancy
How’s N from AA converted to urea?
- Transamination.
- Formation of ammonia.
- Formation of urea
What happens in transamination?
nitrogen part of α-amino group transferred to an α-keto acid to become a new AA (glutamate).
eg of α-keto acids?
α-ketoglutarate, pyruvate, oxaloacetate
Role of transaminases?
enzymes that transfer amino group from AA to α-keto acid
eg of transaminases?
alanine (ALT) + aspartate (AST)
Role of Alanine Transaminase (ALT)?
Alanine + α-Ketoglutarate ⇋ Pyruvate + Glutamate
Role of Aspartate Transaminase (AST)?
Aspartate + α-Ketoglutarate ⇋ Oxaloacetate (oxaloacetic acid) + Glutamate
Why oxidse α-ketoglutarate, pyruvate, oxaloacetate?
- Make ATP in OP
- Converted to glucose (supplementing gluconeogenesis)
Role of Glutamate? .
a way the body can transport potentially toxic nitrogen
Where are transaminases?
in liver
What happens if high levels of AST + ALT in blood?
indicative of liver damage (shouldn’t be found in plasma)
Role of Alanine?
donates its α-amino group to α-ketoglutarate to give glutamate + pyruvate
reaction requires vit B6
What happens to glutamate?
- release ammonia via glutamate dehydrogenase
- yields back α-ketoglutarate
- NAD used for degradation + NADPH for synthesis
Where does transamination occur?
in cytosol
Role of glutamate dehydrogenase
release ammonia from glutamate
Where’s glutamate dehydrogenase?
in the mitochondrial matrix
Which AA don’t undergo transamination?
threonine + lysine
How’s 1g of urea formed from 3g of protein?
Urea contains 48% nitrogen by weight, protein contain 16%
Why’s glutamate useful?
freely interchangeable with α-keto acids + ability to donate / accept ammonium ions
Describe step 1 + 2 of urea formation?
- transamination to glutamate
- oxidative deamination back to α-ketoglutarate
Importance of converting AA into glutamate?
can be transported then re-converted back into something body can use for energy (or transamination again) while re-synthesising the ammonia which is fed into urea cycle
How’s glutamine synthesised + equation?
glutamate formed from transamination combines with free ammonia (or NH4+) generated in tissues
Glutamate + NH4+ + ATP ⇋ Glutamine + ADP
Role of glutamine synthase?
Glutamate + NH4+ + ATP ⇋ Glutamine + ADP
Role of glutamine?
transports the potentially toxic N to the liver
Where does glutamine synthesis occur?
in periphery
glutamine synthase widely distributed in blood vessels with a lot of protein breakdown including blood vessels of liver
Removal of N summary?
- transfer of amino groups to α-ketogluterate to form glutamate
- glutamate oxidatively deaminized to α-ketogluterate (recycled for transamination again or used as energy source in TCA)
- glutamate can accept more N forming glutamine
- glutamine is main transporter of N
- glutamine can donate nitrogen for biosynthesis of AAs, nucleotides, NAD+
What’s the urea cycle?
metabolic pathway for excreting N
restricted in its distribution, being mostly in liver - not in muscle
What does muscle produce?
substrates, but not enzymes
Where does the urea cycle occur?
mitochondria + cytoplasm of hepatocytes
Substrates of urea cycle?
bicarbonate, aspartate, ammonium ions
Where’s ammonium ions in urea cycle from?
released from glutamine or glutamate produced in deamination
Where’s bicarbonate in urea cycle from?
from CO2 as a byproduct of metabolising C skeleton
Role of bicarbonate in urea cycle?
forms the CO2 needed
Describe where chemical components of urea are from?
-2 N atoms:
donated from aspartate
from glutamine/glutamate.
-Carbon C=O from C skeleton via using CO2 that has been produced from its breakdown
Describe how urea cycle + TCA cycle linked?
- CO2 from bicarbonate reacts with NH4+ ions
- forms carbamoyl phosphate
- carbamoyl phosphate reacts with ornithine
- forms citruline.
- citruline reacts with aspartate
- form argino-succinate.
- argino-succinate metabolised to arginine + fumarate
- enzyme arginase forms arginine
- fumarate converted to malate
- malate transported back into mitochondria
- malate converted to oxaloacetate
- process continues
- starting point : aspartate
How’s aspartate formed?
by transamination of α-amino acids, when reacting oxaloacetate with glutamate (an α-amino acid) in mitochondria
How’s carbamoyl phosphate formed + where?
CO2 from bicarbonate + NH4+ using 2 ATP in mitochondria matrix
How’s citruline formed?
carbamoyl phosphate + ornithine
How’s argino-succinate formed?
citruline + aspartate
What’s argino-succinate metabolised to + via which enzyme?
arginine + fumarate
via arginase
How’s malate formed?
converted from fumarate
How’s oxaloacetate formed?
converted from malate
What’s oxaloacetate used for?
- Gluconeogenesis (TCA Cycle)
- Reaction with glutamate in mitochondria to form aspartate (in the transamination reaction) so recycled back into urea cycle
Where does urea cycle occur?
predominantly in hepatocytes (+ kidneys)
Why does the urea cycle occur?
to transform toxic by product of AA breakdown NH3, into less toxic form urea, that can be mobilised + transport to kidneys where excreted via urine
Describe urea cycle
- AA metabolism occurs
- extra NH4+ + CO2 using 2 ATP -> carbamoyl phosphate
- ornithine moves into matrix
- ornithine + carbamoyl phosphate -> citrulline
- citrulline moves to cytoplasm
- citrulline + aspartate -> argino-succinate
- argino-succinate metabolised -> arginine + fumarate
- 2nd amino group that came from aspartate, ends up on the arginine.
- C skeleton found on aspartate, ends up on fumarate (so C skeleton of the aspartate is fumarate)
- fumarate -> malate
- malate -> oxaloacetate
- hydrolyse arginine using H2O (where the O comes from in urea)
- urea is removed
- ornithine is formed which is recycled into matrix
Role of branched AAs + eg?
used for this energy
eg leucine, valine, isoleucine
Role of branched AAs + eg?
used for energy
eg leucine, valine, isoleucine
How are remaining AA dealt with?
- N transferred to alanine via glutamate + pyruvate
- Circulating/intracellular glutamate made into glutamine
What can muscle export?
alanine major export of muscle that is actively being broken down (due to exercise or starvation).
Describe cycling of alanine?
-branched AAs taken: C skeleton used for energy production + NH4 converts pyruvate -> alanine
-alanine exported into blood + travels to liver
alanine -> glutamate via transamination (reacting with α-ketogluterate) also producing a pyruvate
-pyruvate enters gluconeogenic pathway -> glucose
-glucose transported in blood back to muscle for energy
-glutamate used with CO2 generated -> urea
Role of the glucose-alanine cycle?
get rid of NH4+ from SM to transport to liver where that ammonium can be fed into the urea cycle
Describe glucose-alanine cycle?
- in SM, NH4+ formed from AA metabolism, combines with pyruvate -> alanine
- alanine transported via bloodstream into hepatocytes
- alanine -> pyruvate + glutamate (NH4+) via transamination with α-KG
- NH4+ disposed into urea cycle
- pyruvate -> glucose
- glucose transported to SM via blood stream, so it’s recycled
- glucose -> pyruvate in SM + reacts with NH4+
Why’s it called glucose-alanine cycle?
utilize glucose to form pyruvate, which is used to attach NH4+ and form alanine
Describe glutamine synthetize process?
- uses ATP to attach NH4+ to glutamate -> glutamine.
- glutamine can move into hepatocyte
- broken down into glutamate, releasing NH4+
- fed into urea cycle
2 types of AA?
ketogenic AA + glucogenic AA
What are ketogenic AAs?
form ketone bodies
What are glucogenic AAs
used by liver to produce glucose
Purpose of AA broken down being converted into intermedietes of TCA cycle?
can convert this back to glucose
