Amino Acid Catabolism Flashcards
Amino acid catabolism includes:
- Removal of alpha amino group as
- Converion of ammonia into
- Conversion of remaining amino acids carbon skeleton into
- Ammonia
- Urea
- TCA cycle intermediates
3 disposal methods of body nitrogen?
Transamination, deamination, and transport of ammonia
Transamination:
- What is happening?
- So acceptor of amino group is?
- Is ammonia released?
* 4. Requires? - 3 exceptions (do not go through transamination)
- Transfer of amino group from an amino acid to keto acid to form a newer keto acid and newer amino acid respectively
- Keto acid
- No
* 4. Pyridoxal phosphate (vitamin B6)(PLP) - Lysine, threonine, and proline ~sometimes proline does
Transamination is done by a family of enzymes called
Where are these enzymes located
How are these enzymes named?
Amino transferase/transaminase
In cytsol/mitochondria of liver, and muscle
After the specific amino group donor
Alanine + alpha ketoglutarate transaminate to give you what two things?
What enzyme does this?
Pyruvate (keto acid) and glutamate (amino acid)
ALT
What does aspartic acid + alpha ketoglutarate transaminate to?
What enzyme does this
Oxaloacetate and glutamate
AST
All the amino nitrogens that undergo transamination can be concentrated in?
Glutamate (and acceptor group is almost always alpha ketoglutarate)
Why are ALT and AST used for diagnosis?
They are nonfunctional enzymes which are not supposed to be present in the blood - if they are, then you know there is a pathology
If serum AST is more specific than ALT, what diagnosis does that indicate
Non hepatic diseases (MI and muscle disorders)
If serum ALT is more specific than serum AST, what diagnosis does that indicate?
Hepatic diseases
Are these transamination reactions reversible?
Yes
Deamination:
- Function of this type of reaction?
- Oxidative deamination is done by which enzyme
- Reversible?
- Location?
- Removal of amino group as ammonia
- Glutamate dehydrogenase
- Yes
- Mitochondrial matrix of the liver and kidney
What is the only amino acid that undergoes rapid oxidative deamination
Glutamate
Result of oxidative deamination
Release of a free ammonium ion (but body has to get rid of this or it can be toxic)
- Disposal of amino acids is called ___
2. Synthesis of amino acids is called __
- Oxidative deamination
- Reductive amination
~same process just reversed
Nitrogen mainly travels in which two amino acids?
Alanine and glutamine
- Glutamine transports ammonia from __ to __
2. Alanine transports ammonia from __ to __
- Peripheral tissue to liver
2. Muscle to liver
- In most of the tissues, glutamate gets converted to glutamine by which enzyme?
- What happens in liver, kidney, and intestine and by which enzyme?
- Glutaminase also does what?
- Glutamine synthase
- Glutamine to glutamate by glutaminase
- Releases ammonia to liver
What is the best carrier of ammonia group?
Glutamine - gets synthesized in most tissues then gets carried to liver/kidney/intestine where glutaminase works on it
Glutamine transport is major mechanism for detoxification of?
Ammonia in the brain
Liver, kidney, and intestine are only tissues that can?
Excrete ammonia
Source of NH3 in the intestine?
Bacterial flora
- Glutamine is removed from circulation by?
- What happens to most of the ammonia from when glutamine is converted to glutamate
- What is this mechanism important for
- Kidneys
- Excreted in the urine has NH4+
- Maintaining acid base balance of the body
What ion can be exchanged for NH4+
What does this help with
When would this be handy?
H+
Acid base balance
When you are in acidosis or alkalosis
Glutamate in liver gets excreted as?
Glutamate in kidney gets excreted as?
Glutamate in intestine?
Urea
Ammonium ion in the urine
Enters portal circulation then taken to the liver to form urea
Source of glutamine in the intestine?
Proteolysis of dietary protein
Urea cycle:
- Location of synthesis of urea?
- Urea clearance is a measure of?
- Urea is soluble in?
- Mammals are primarily
- Cytosol and mitochondria of the liver
- Glomerular filtration rate (GFR)
- Water
- Ureotelic - producing urea, not uric acid
Main function of urea?
To get rid of ammonia
What is CPS 1 involved in?
CPS2?
Urea cycle
Nucleotide synthesis
Urea cycle requires?
2 ATP
First amino group (nitrogen) utilized in urea cycle is provided by? Second?
First-ammonia
Second-aspartate
CPS1 (carbamoyl phosphate synthetase 1) is utilized in the first step of urea cycle. What is it combining?
This reaction requires?
Ammonia and CO2 to make carbamoyl phosphate
Mg2+
What is significant about CPS1?
What does CPS1 require?
Rate limiting step
Requires an activator (NAG)
NAG is synthesized from?
What does NAG do to activate CPS1?
Acetyl CoA and glutamate by NAG synthase
Enhances its affinity for ATP
When will intrahepatic concentration of NAG increase?
After a protein rich meal
Second step of urea cycle:
__ and __ combine to form __ by which enzyme?
Carbamoyl phosphate combines with ornithine to form citrulline by OTC
What does oral neomycin administration do?
Reduces intestinal bacteria - decreased NH3
In renal failure patients, what enzyme works on urea?
Urease (important source of NH3 in feces)
~so check for release of urea to determine if there is kidney dysfunction
Normal ammonia level
How much to be considered hyperammonemia ?
5-50 mmol/L
1000 mmol/L or more
Signs of hyperammonemia
Very sleepy during the day, flapping tremors, liver enlargement, SOB, papilledema (eyes), rigid trunk, and loss of coordination
~so CNS involvement
Main causes of hyperammonemia
What does it cause?
Liver disease (cirrhosis), toxic mushrooms, alcoholism, biliary obstruction
~so anything that affects the liver
Causes increased levels of circulating ammonia
Hereditary hyperammonemia
- Deficiency in what enzymes
- Treatment?
- Either CPS1 (type 1) or OTC (type 2)
2. Limiting protein in diet/ pheyl butyrate
Difference between CPS 1 deficiency and OTC deficiency presentation
CPS1 has no increase in orotic acid and uracil, OTC does
