Protein Breakdown and Urea Formation Flashcards
What is dietary protein broken down into?
Amino acids
Likewise, amino acids can be converted into body proteins, and the synthesis and degradation of proteins and amino acids is equal
What can amino acids be further broken down into?
- Biosynthetic products
- Nitrogen free intermediates (This is the carbon skeleton, left behind after the ammonia is removed)
- These are further converted into glucose, CO2, H2O and ketone bodies
- Ammonia (NH3)
- This enters the urea cycle, metabolised by the liver and converted into urea, and is excreted by the kidneys
Outline the metabolism of glucose. What’s the name of the proces in which glucose is synthesised, and what can it be converted into when glucose lvls are too high?
- Glucose converted into pyruvate via glycolysis
- Gluconeogenesis is the process of synthesising gluocse from pyruvate
- Glucose can be converted into glycogen by liver, can also take place in skeletal muscle and kidney, vice versa when lvls are too high or low
What is pyruvate converted into?
Acetyl CoA, which reacts with citric acid to form citrate, enters TCA cycle. Generates NADH and FADH, used in oxidative phosphorylation to yield much more ATP
Acetyl CoA is used for fatty acid synthesis in the liver, and is formed when FAs are degraded
How do amino acids enter the TCA cycle?
After being converted to either Acetyl CoA, pyruvate, oxaloacetae or succinyl- CoA
How do amino acids differ from carbs and fats?
Amino acids are either used or broken down but NOT stored
What are amino acids converted into?
2 parts:
- Carbon skeleton (alpha-keto acid), used for:
- Energy metabolism
- Biosynthetic pathways
- Nitrogen (ammonia/ammonium ion) used for:
- Nitrogenous compounds
- Urea
Converted via transaminase/aminotransferase enzyme
Describe the fate of the carbon skeleton
Carbon skeleton formed from breakdown of amino acids
2 forms of amino acids:
- Ketogenic - Broken down to form acetyl CoA/ acetoacetyl CoA, form ketone bodies
- Glucogenic - Broken down and fed into TCA cycle, forms oxaloacetate which is syphoned off, forming phosphoenol pyruvate, which is then used to synthesise glucose
Some amino acids are both glucogenic and ketogenic
Describe oxidative deamination
Ammonia can be released from glutamate as glutamate is converted into alpha-ketogluterate. This is mediated by glutamate dehydrogenase, which is in the mitochondrial matrix. This process is oxidative deamination
What happens to free ammonia in non-hepatic tissue?
Free ammonia generated in non-hepatic tissue combines with glutamate to produce glutamine + ADP. This is mediated by glutamine synthase
Glutamine is soluble and readily transported in the blood, so is able to safely transport the ammonium ion to the liver
Why must ammonia be removed?
It’s toxic, so must be removed safely. Lvls of ammonia in the blood are low
In mammals, what is ammonia converted into?
Into non-toxic neutral compound urea, and excreted in urine
Amino acid nitrogen is transferred to urea in 3 steps:
- Transamination
- Formation of ammonia
- Synthesis of urea
Where does the urea cycle take place, and what substrates and molecules are required?
Urea cycle = Excretion of Nitrogen
- Takes place in mitochondria and cytoplasm
- NEEDS:
- Enzymes - These are present in the liver but NOT muscle
- Bicarbonate
- Aspartate
- Ammonium ions (released from glutamine or glutamate)
How is urea formed?
CO2 from carbon skeleton or bicarbonate is able to bind to amine groups of glutamine and aspartate
Describe the urea cycle
When CO2 reacts with ammonium ions from glutamine:
- CO2 from bicarbonate reacts with ammonium ions from glutamine forms carbamoyl phosphate
- Carbamoyl phosphate reacts with ornithine to form cirtulline
- Citrulline formed in the mitochondria is exported out into the cytosol, in exchange for ornithine synthesised in the cytosol.
- Citrulline in the cytosol reacts with aspartate, forming arginino-succinate
- Aspartate is formed when alpha amino acids react with an alpha-keto-acid (transamination) e.g. oxaloacetate
- Arginino- succinate forms arginine and fumarate
- Arginine produces urea and ornithine, this reaction is mediated by the enzyme arginase. This allows the cycle to continue
- Fumarate is converted into malate and malate then into oxaloacetate, this allows for the formation of aspartate
Where are the enzymes glutamate dehydrogenase and aspartate aminotransferase found?
Mitochondria of liver
What is transamination?
When amino acids react with alpha keto acids to produce a new amino acid and a new alpha keto acid. This is mediated by transaminase/aminotransferase
The amino acid amine group is transfered to an alpha-keto acid. The amino acid becomes a keto acid, and the alpha-keto acid acceptor of the amine group is converted into the corresponding amino acid
NOTE:
- Alpha-ketoglutarate, pyruvate and oxaloacetate are alpha-keto acids
What are the 2 amino acids that don’t undergo transamination?
- Threonine
- Lysine
What are the 2 most important transaminases?
- Alanine (ALT)
- Reacts with alpha ketoglutarate via transamination. Alpha ketoglutarate becomes glutamate, and alanine is converted into pyruvate
- Pyruvate can be used in the TCA cycle and ETC to make ATP
- Aspartate (AST)
- Reacts with oxaloacetate via transamination. Oxaloacetate becomes Aspartate, glutamate is converted into alpha ketogluturate
What are high levels of AST and ALT in the blood indicative of?
Tissue damage, particularly liver and cardiac muscle
What can oxaloacetate and alpha-ketoglutarate be used in the liver for?
Glucose synthesis via gluconeogenesis
How does the muscle metabolise proteins?
- Enzymes of the urea cycle aren’t present
- In prolonged exercise or starvation branched amino acids are used for energy (leucine, isoleucine and valine)
- 2 routes used to transport nitrogen to liver
- Alanine
- Glutamine
If nitrogen were transported via amino acid alanine:
- Glycogen is broken down to produce glucose, which via glycolysis produces pyruvate
- Pyruvate reacts with the ammonium ions formed from the breakdown of amino acids, this forms alanine via transamination reaction
- Alanine can be transported in blood to liver
- Enzyme alanine transaminase converts alanine into glutamate and pyruvate
- Glutamate is broken down by glutamate dehydrogenase, releasing an ammonium ion, which can then enter the urea cycle
- The pyruvate is used to synthesise glucose via gluconeogenesis, where it’s then transported back to muscle
What is nitrogen balance?
Synthesis of new proteins balanced by degradation of proteins, so equal amounts of nitrogen are synthesised/uptaken and excreted
What is a positive nitrogen balance?
Build up of body proteins, so greater proteins being synthesised (growth, pregnancy, exercise, tissue hypertrophy). This is under the influence of anabolic proteins. Greater amount of nitrogen being produced than is being lost.
