Nitrogen Metabolism/Urea Cycle Flashcards
What are the dietary fuels
- Carbohydrates - sugars and starches ( store glycogen in skeletal muscle and liver)
- Lipids (store as triglycerides in adipose tissue)
- Proteins - amino acids
We dont store amino acids ; we ____them down
break
No ____ in carbohydrates of lipids
nitrogen
Have to convert nitrogen to ____
urea
where does urea cycle occur
liver
When are aa oxidized for energy?
- normal protein turnover
- starvation/diabetes (uncontrolled)
- protein rich diet (Atkins)
what is nitrogn balance
what you take in vs what you excrete; if intake and excretion are equal it is called N balance; healthy adults
What is + nitrogen balance
Holding all the nitrogen you take in (intake> loss); growing children, pregnancy, illness/trauma recovery
What is - nitrogen balance
loss is greater than your intake; excreting a lot of Nitrogen in urine; you get edema
What is kwashiorkor
The condition of the first born when the second child arrives. the first child who was on breast milk that had all the essential aa’s is put on grain diet thats missing essential aa: muscle waisting metabolism!
what maintains fluid in bloodstream vs going into tissues
colloid osmotic pressure; proteins of blood maintain colloid osmotic pressure that draws water in but if your lose protein from your blood bc your using it for energy production the main protein you lose is albumin which prov bulk of colloidic osmotic pressureAs osmotic pressure dec fluid leaves blood and goes into tissues. You get edema.
What is ureotelic
excrete urea- terrestrial animals. 86%
what is ammonotelic
excrete ammonia directly - bony fishes. 2.8%
what is uricotelic
excrete uric acid- birds and reptiles. You dont want a bird with a big bladder; birds conserve water in this way. 1.5%
what does the other 4% nitrogen come from
Creatine. Which comes from muscle
What is peristalsis and stomach acid important for
open up proteins and dentature them; make them more accesible to proteases and cleave them into ind aa that can be asorpeed by brush border in intestine.
What do mucosal cells produce
Gastrin; hormone that binds to receptors on T cells that cause them to secrete pepsinogen (inactive precursor protein) and it also makes histamine which makes HCl via parietal cells.
What is the end result of the digestive system
liquid chyme
How does pepsinogen turn to pepsin
Pepsinogen–>pepsin–>active and auto cleaves itself which starts process of protein digestion slightly
Secretion initiated by CNS input is via
acetylcholine
What does atropine, probanthine do
blocks acetylcholine interaction with muscarinic receptors.
What does cimetidine or ranitidine block
histamine interaction with H2 receptors
What are the two hormones that the intestinal mucosa produces
cholecyskokinin: causes gall bladder to secrete bile salts to emulsify fats.
secretin: targets exocrine pancreas; secretes things into intestine which secretes zymogens and bicarbonate.
What is the enzyme that the intestinal mucosa produces:
enteropeptidase which activates trypsinogen–>trypsin–> pancreatic zymogens: pro carboxypeptidase
What are the enzymes involved in gall bladder and bile salts
chymotrypsinogen, procarboxypeptidase and proelastase
what do secretory cells secrete and what is the end result of it
zymogens and bicarbonate. End result is a single amino acids!
What are the different classes of aa that the intestine uses for active transport systems
- neutral
- basic and Cys
- imino and Gly
- acidic
- beta amino acids: beta alanine, taurine
What is Hartnup’s disease
similar to pellagra; niacine deficiency; bc this transporter transports tryptophan. you get dermatitis, diarrhea and dementia and inflammation of tongue and oral cavities.
how do you get amino acids
from intracellular protein or dietary proteins
what do the carbon skeletons do
Go into diff pathways: TCA cycle for energy production, ketone bodies which break down into acetyl coA for fatty acid synthesis, or glucose synthesis or glycogen storage
What are the 3 basic processes
- Transport nitrogen to liver to synthesized into urea and excreted: transamination (moves nitrogen from aa to glutamate), glutamine synthase.
- nitrogen removal in liver: glutaminase, glutamate dehydrogenase
- Production of urea
what are peripheral tissues
center of universe is liver so peripheral tissues are everything else
what do peripheral tissues use in transamination
alpha keto gluturate –> funnel N to glutamate –> glutamine
How does skeletal muscle transaminate
doesnt want to give up alpha keto glutarate (bc in TCA cycle) instead it sacrifices pyruvate to form alanine. Glutamine and alanine then travel through bloodstream to liver.
What aa are most in blood
- glutamine
- alanine (these two bc they use N groups to transport to liver)
- all others are pretty low
How does the glucose alanine cycle work in skeletal muscle
Pyruvate from skeletal muscle glucose metabolism is converted to Ala, sent to liver and converted back to glucose and sent back to muscle
What is first step of nitrogen cycle
Transamination: Peripheral tissues will send nitrogen to liver via glutamine or alanine
What are the major transaminases
- Glutamate Oxaloacetate Transaminase (GOT) which makes aspartate aminotransferase (AAT)
- Glutamate Pyruvate Transaminase (GPT): makes alanine amino transferase (ALT)
How do transamination reactions occur?
swap positions of nitrogen group and keto group.
Reactions occur in pairs. All aa can transaminate with alpha KG except:
Lysine, Thr, and Proline
Which cofactor does it require
B6. (pyridoxal phosphate and pyridoxamine phosphate)
What is second step
Alpha Ketoacid (usally alpha KG) picks up nitrogen group and comes off as glutamate.
What if you used something else other than alpha KG
Pyruvate; goes off as alanine.
Heart and liver has, but liver also has a lot of :
GOT; GPT. Both elevated it points to liver disease.
What enzyme converts glutamate to glutamine synthase.
Glutamine synthase. Highly regulated! Bc once you make glutamine it gets transported out and goes to liver. When this happens it converts to urea and then gets excreted out forever.
What are the allosteric modifiers in glutamine synthase regulation
amino acids, nucleotides, N compounds
If glycine and alanine levels drop then
inhibition would be lost. Make glutamine for protein synthesis.
Once in the liver, the nitrogens will be removed to be converted to _____. Alanine from muscle will transaminate with alpha KG to make _____. Glutamine will have side chain nitrogen removed via glutaminase and become _____
urea. Glutamate. Glutamate.
What are the two things that glutamate does
- Transaminate with OAA to make Asp which will be used in the urea cycle
- Undergo oxidative deamination via glutamate dehydrogenase to regenerate alpha KG and NH4 which be used in the urea cycle.
Hydrolytic deamination uses ____to exchange with NH2
water
What is step 3 of the nitrogen cycle
- most ammonia is converted to urea in the LIVER
- You get 1 N from NH4, and 1 N from Asp
- You get 3 ATPs, and 4 high energy bonds
Portions of the cycle occur in cytosol, other parts occur in:
mitochondria
What are the nitrogen excretion products
86% urea, 2.8% ammonia, 1.5% uric acid
What are normal BUN levels
8-25 mg% or 2.9 -8.9 mM
What does high urea or BUN indicate
kidney problem; liver does its job of making urea
What does high NH4+ indicate
liver problem; cause the liver doesnt convert ammonia to urea and some ammonia is escaping into bloodstream
Oxaloacetate makes aps. Puruvate makes____
alanine
What is the Urea Cycle
Starts in mitochondria matrix bc of free amonia. Take CO2 + free amonia and hook them together to make carbamoyl phosphate which condenses with citrulline which leaves mitochondria to transaminate to aspartate. It makes argeninosuccinate which gets transferred to fumerate which goes to TCA cycle. This also releases argenine wthic gets cleaved with water, regenerates to ornithine and releases UREA.
What is the committed step of the urea cycle
carbamoyl phosphate synthesis; occurs in mitochondira
What enzyme is responsbile for carbamoyl phosphate
carbamoyl phosphate synthetase I. This reaction is irreversible.
What are non standard aa
no codon in genetic code for ornithine and citrulline
Krebs Bicycle refers to oxaloacetate giving off aspartate which gets turned to :
fumerate
why is ammonia so toxic
- depletes the TCA cycle intermediate alpha KG and thus NADH production which results in dec ATP production. Bran in highly ATP dependent.
- Depletes Glu and gammy aminobutyrate (GABA) both are neurotransmitters
- Build up of Gln inc. intracellular osmotic balance; water enters astrocytes; brain swells.
What are genetic defects in urea metabolism
- usually cause mental retardation, seizures/coma
2. treatment requires careful control of diet and admin of detoxifying compounds.
