W6 Protein breakdown + urea formation Flashcards
Metabolism of AAs
Broken down but not stored
Two parts
The carbon skeleton
Nitrogen
Carbon skeleton
Energy metabolism
Biosynthetic pathways
Removal of Nitrogen
Nitrogen is toxic so has to be removed safely
In mammals the nitrogen is converted to the non-toxic neutral compound urea and excreted in the urine
Amino acid nitrogen is transferred to urea in three steps
Transamination, formation of ammonia and formation of urea
Transaminase
aminotransferase
AA a reacts w/alpha-keto acid B
AA a into alpha-keto acid a
alpha-keto acid B into AA b
NH3 transfer to alpha-keto acid B from AA a
Alanine
A transaminase (High levels in blood indicative of liver damage)
Transfer an amino group from an AA to α-keto acid
Alanine + alpha-ketoglutarate ⇋ pyruvate + glutamate
Preffered direction = →
Requires pyridoxal phosphate derived from vitamin B6
Aspartate
A transaminase (High levels in blood indicative of liver damage)
Transfer an amino group from an AA to α-keto acid
Aspartate + alpha-ketoglutarate ⇋ oxaloacetate + glutamate
α-ketogluterate and oxaloacetate can be oxidised or converted to make glucose
Preferred direction = ←
AST funnels the amino groups from glutamate to OAA to make aspartate for the urea cycle
Requires pyridoxal phosphate derived from vitamin B6
Transamination of AAs
All amino acids except threonine and lysine undergo transamination
Formation of ammonia
Oxidative deamination
Ammonia formed is a substrate for the urea cycle
Glutamate → alpha-ketoglutarate by glutamate dehydrogenase (NADH + NH3 released)
NADP (synthesis)/NAD (degradation) can be used
Elimination of free ammonia
Free ammonia generated in tissue combines with glutamate to give glutamine
Glutamate + NH4^+ + ATP → glutamine + ADP
By glutamine synthase
This is a way of transporting more than one residue
Removal of Nitrogen
The transfer of amino groups to α-ketogluterate to form glutamate
Glutamate can accept more nitrogen forming glutamine
Glutamine is the main transporter of nitrogen
Glutamine can donate nitrogen for the biosynthesis of amino acids, nucleotides, amino sugars and NAD+ (also for urea synthesis)
The urea cycle summary
The means of excreting nitrogen
Enzymes are present in the liver but not muscle
Takes place in the mitochondria and the cytoplasm
Substrates are bicarbonate, aspartate and ammonium ions (released from glutamine or glutamate)
2 cycles linked together
Formation of urea
Uses 2 amino groups
Aspartate = from transaminase reaction
Bicarbonate = from breakdown of carbon skeleton
Ammonium ions
Urea cycle
Oxaloacetate (from TA) → aspartate → argininosuccinate → Fumarate → Malate and then back to oxaloacetate
Argininosuccinate → arginine → orinithine → citrulline (by addition of carbamoyl phosphate formed by CO2 + NH4+) and then back to argininosuccinate
Why no urea cycle in muscles
Because no arginase
Reaction catalyzed:
Arginine + H2O → ornithine + urea
It is the final enzyme of the urea cycle
Muscle
In prolonged exercise or starvation branched amino acids are used for energy
Enzymes of the urea cycle not present but has transaminases
Two routes of transport used to transport nitrogen to the liver
Alanine and glutamine
Nitrogen transferred to alanine via glutamate and pyruvate
Glutamate is made into glutamine
Glucose alanine cycle
In liver:
Alanine → pyruvate + glutamate (which is then converted into NH4+ then urea)
Pyruvate → glucose
Glucose through blood into muscle
In muscle:
Glucose (from liver + glycogen) → pyruvate → alanine
Alanine also from branch chain AAs into NH4+ (also producing carbon skeletons + using cellular respiration). Then NH4+ combine w/pyruvate = alanine
Ketogenic AA
Not used to generate glucose but will be used to generate ketone bodies
Glucogenic AA
Feed into points of krebs cycle, in liver, that will generate excess intermediate which will lead to generation of oxaloacetate
Oxaloacetate used for glucogenic pathway to form glucose
Nitrogen balance
Proteins are structural or functional
There are no specific protein stores
Amino acids are supplied in the diet
Excess protein is broken down and excreted
Positive nitrogen balance
AA pool going to body > body protein to AA pool
Dietary protein > normal (feeding into AA pool)
Urea + other products = normal levels
Exercise and tissue hypertrophy
Response to anabolic hormones
Growth/pregnancy
Negative nitrogen balance
Body protein into AA pool > than AA pool into body protein
AA pool into urea, other products > than when normal nitrogen balance
Response to catabolic hormones lack of anabolic ones (e.g. in diabetes)
Wasting diseases, burns, trauma
Cancers
