Nitrogen Metabolism Flashcards
What are some dietary fuels?
Carbohydrates (sugars & starches)
Lipids (fats)
Proteins (amino acids)
When are amino acids oxidized for energy?
Normal protein turnover
Starvation
Uncontrolled diabetes mellitus
Protein Rich Diet (Atkin’s)
N Balance
Intake = Loss
(+) N Balance
Intake > Loss
Growing children, pregnancy, illness/trauma recovery
(-) N Balance
Loss > Intake
Starvation
What is kwashiorkor?
Muscle Wasting Metabolism
Define Ureotelic.
Beings that excrete Urea like terrestrial animals.
86%
Define Ammonotelic.
Beings that excrete Ammonia directly like bony fish
2.8%
Define Uricotelic.
Beings that excrete Uric Acid like birds & reptiles
1.5%
Where does the other 4.5% of excreted ammonia products come from?
Creatin
What do the mucosal cells of the stomach excrete?
Gastrin and Histamine
What do the parietal cells of the stomach excrete and what are they activated by?
Secretes HCl
Activated by Histamine from the Mucosal Cell
What does gastrin from the mucosal cells activate?
Chief cells which secrete Pepsinogen
What is the action of Atropine and probanthine on the digestive system?
Blocks ACh integration with muscarinic receptors
What is the action of Cimetidine (Tagamet) and ranitidine (Zantac) on the digestive system?
Block histamine interaction with H2 receptors
What CNS Neurotransmitter initiates secretion in the stomach?
Acetylcholine
What two hormones and one enzyme do the intestinal mucosa produce?
Cholesistokinin, Secretin, Enteropeptidase
What does the pancreas excrete?
The secretory cells secrete zymgens and HCO3-
What is the end result of pancreas excretion?
Single Amino Acids
What does a deficiency in Neutral amino acids result in?
Hartnup’s Disease (NAD def)
Can free amino acids be stored?
No, they are catabolized. There is no way to store them.
What are the products of amino acid catabolism?
Ammonia (NH4+)
Alpha-keto acid carbon skeletons
What is ammonia converted into?
To Urea for excretion
What are alpha-keto acid carbon skeletons converted into?
Pyr, AcCoA or TCA cycle intermediates
What are the 3 basic processes of nitrogen metabolism?
1) Transport nitrogen to liver
2) Nitrogen removal in liver
3) Production of urea
How is nitrogen transported to the liver?
Transamination
Glutamine synthase
How is nitrogen removed in the liver?
Glutaminase
Glutamate dehydrogenase
What is the Glucose Alanine Cycle in a nutshell?
Pyruvate from skeletal muscle glucose metabolism converted to Ala, sent to liver & converted back to glucose & sent back to muscle
What are some major Transaminases?
Glutamate-Oxaloacetate Transaminase (GOT)
Glutamate-Pyruvate Transaminase (GPT)
What are some minor transaminases?
Branched chain aminotransferase
Tyrosine aminotransferase
Ornithine aminotransferase
What forms of Vitamin B6 are involved in transamination reactions?
Pyridoxal phosphate
Pyridoxamine phosphate
In what cases would serum levels of transaminases go from normally very low to elevated levels?
Heart Attack and Liver Damage
Damaged cells leak enzymes into bloodstream
What serum levels should yo check if you think a heart attack may have occurred?
SGOT SGPT CK LDH If both CK and LDH raised then 100% diagnostic
What two intermediate steps are needed for nitrogen transport to the liver?
Transamination
Glutamine synthase
What two intermediate steps are needed for nitrogen removal in the liver?
Glutaminase
Glutamate Dehydrogenase
Why is the glutamine synthase step of nitrogen transport so important?
It commits the nitrogen to disposal and no other process and is thus highly regulated.
What is glutamine important for?
Main repository for NH3
What are the functions of glutaminase?
Hydrolytic deamination that uses water to exchange with NH2.
Also used in kidneys to supply ammonia for acid neutralization in urine.
How much of the bodies nitrogen is excreted as Urea?
80%
Where is more ammonia converted to Urea?
In the Liver
How energy costly is the urea cycle?
Very
Uses 3 ATP’s and 4 high energy bonds
What does to much urea in the body mean?
Gout
What does increase BUN levels mean?
Kidney problem
What does BUN stand for?
Blood urea nitrogen
What does increase NH4+ levels mean?
Liver problem
What is the committed step (rate limiting step) of the Urea Cycle?
Carbamoyl phosphate synthesis via carbamoyl phosphate synthetase I (an irreversible reaction)
Which portion of the urea cycle occurs in the mitochondrial matrix?
The 1st portion
What happens when NH4+ is in excess?
alpha-KG is removed from the TCA cycle for transamination to Glu for conversion to Gln for export to liver
When would levels of NH4+ increase?
Cirrhosis caused by alcoholism, hepatitis or genetic defects
Elevated ammonia levels affects which part of the body profoundly.
The brain
Problems include: decreased ATP, depleted Glu and GABA, and brain swelling due to osmotic imbalance.
What are some effects of genetic defect in urea metabolism?
Life threatening
Usually cause mental retardation, seizures, and/or coma
How are genetic defects in urea metabolism treated?
Requires careful control of diet and administration of detoxifying compounds