Metabolismul aminoacizilor –

balanta azotata
 Aminoacizii
• Twenty in proteins
– More involved in metabolism
– Loads of different side chains
– So pathways of formation and disposal varied
and complex
• Synthesis and degradation of proteins
– Each under different control
– Hard to generalize
 Daily Flux

10 kg pool

Intake 100 g Loss 100 g

300 g turnover
16 g nitrogen 3% per day skin 0.5 g nitrogen
urea 16 g nitrogen
faeces 2 g nitrogen

Turnover varies massively between tissues: muscle 2%, intestine 15%

But muscle is greatest bulk of protein.
 Principles
• Liver important
– First place amino acids go from intestine
– Conversion of amino acids
• Especially to glucose
– Processing of amine groups
• Urea synthesis
• Degradation enzymes have very high Km
– Not ‘controlled’
– Only affected by [amino acid]
– So excess amino acids are degraded
 Facts
• Amino group
– Fixed nitrogen is quite precious
• Recycle if possible
– But ammonia is toxic
• So need to convert to non-toxic product
• Carbon skeleton
– Normally a 2-oxo acid
• Oxidized or converted to carbohydrate or fat
 Transamination
• Shuffling of amino groups
• Involves alpha-keto (2-oxo) acids
– Main acceptors
• Pyruvate  alanine
• 2-oxo glutarate  glutamate
• Oxaloacetate  aspartate
• These are involved in other pathways
– Glycolysis, Krebs Cycle
 Other Key Reactions
• Glutamate dehydrogenase
– Oxidative deamination of glutamate
• Regenerates 2-oxoglutarate
• Releases ammonia
• Glutamine synthesis
– Using glutamate and ammonia
• Glutamine effectively carries two amino groups
– Reaction reversible
 Essential Amino Acids
• Can’t be synthesized by us - Sometimes conditional on age/situation
 Getting a Good Mixture
• Protein quality
– Meat generally is very high in proteins
• “Standard” is egg
– Beans are low in methionine
– Lysine relatively low in grains
• Protein malnutrition
– If you are lacking in one amino acid, you may not be
able to make an entire protein
– All the other amino acids then ‘in excess’
 Amino Acid Fluxes
• After feeding
• Portal vein (into liver)
– Mixture reflects protein composition
– 20% branched chain amino acids
• Leucine, isoleucine, valine
• Hepatic vein (out of liver)
– 70% branched chain amino acids
• Veins from muscle
– Branched chain amino acids removed
 During Starvation
• Hypoinsulinemia stimulates proteolysis
• Muscle releases all amino acids
– But large amount of alanine & glutamine
• These are preferentially taken up by liver
– Small amount of branched chain amino acids
• Where has the alanine come from
– From pyruvate transamination
• Which needs glycolysis from glucose
 Amino acids
blood

Protein synthesis

Cell protein
proteolysis

glycolysis
glucose pyruvate Amino acids 2-oxoglutarate

alanine 2-oxoacids glutamate

oxidation

glutamine
CO2

Export to
liver Export to
liver
Ciclul glucoza - alanina
 Processing Amino Acids
• During normal turnover
– Many amino acids escape re-synthesis
• Oxidized
• During starvation
– Or other times when there is high proteolysis
• When diet is rich in protein
– Surplus amino acids
• Issue is always…
– How to deal with amine groups
– What to do with carbon skeletons
 Dealing with amine groups
• Urea Cycle
– Liver only
• Glutamate is the main substrate
– In mitochondria, oxidative deamination
• Giving 2-oxoglutarate and ammonia
– Ammonia quickly ‘fixed’ into carbamoyl phosphate
– Glutamate also transaminated to aspartate
• Carbamoyl Phopshate and aspartate
– combine to give urea
Ciclul
UREEI
 General Principle
• Carrier is ornithine
• Reacts with carbamoyl phosphate
– Giving citrulline
• Now add –NH2 from aspartate
– Releasing fumarate, a Krebs intermediate
• Split off urea
– Regenerating the ornithine
 Urea
• Non-toxic
– Can be present in blood at mM levels
– Cleared by kidneys
• Fish can secrete ammonia
– Very dilute!
– Ammonia very toxic to us

• Birds excrete mainly uric acid

• Related diseases: Cirrhosis, Renal failure

REZUMAT