Jan31 M1-Protein Metabolism in Health and Disease Flashcards
2 aa that are ntrs
glutamate and glycine
how many different aa intracellularly and 2 special ones
21 including proline (imino acid) and selenocysteine
N % of protein mass
16% (prots are 16% N)
how to find amount of protein in a sample
get mass of N in it and multiply it by 6.25
protein to total mass ratio in BCM and what occupies the rest of total mass
1:5. 200g protein for 1kg of BCM. water is the rest
1g protein for 4g water
2 reasons dietary prot is essential
- inefficient turnover (not all aa reused): obligatory N loss (some aa reduced for E)
- aa abso and incorporation in endogenous prots is inefficient
necessary and required daily prot
- 65g per kg
0. 80 per kg
what happens if eat too much protein
N balance stays 0. the excess aa are catabolized
biologic value of a protein (food) and examples
adequacy of a food’s essential aa profile
egg and whole milk score of 1. meat, fish, etc. close to 1. rice and beans = 0.5
3 types of diseases where protein requirement is increased
- malabsorption
- protein loss
- protein-catabolic (ex. sepsis)
what determines rate at which body is losing or gaining protein (practically)
N balance (Nin - Nout)
how to estimate daily N excretion
urinary N + 4g (bc urinary N is 80% of N loss daily)
how liver gets N for urea or temporary storage and why
through NEAAs interchanging their NH2 and become their corresponding ketoacid when they give it.
bc free N is highly toxic
molecule of entry into urea cycle and how many NH2 in urea
glutamate.
urea has 2 NH2
3 steps of urea synthesis
- aa from blood (mostly glutamate) reach liver mt
- glutamate releases NH3 and eventually this becomes citrullin in mt (many steps)
- citrulline goes to cytosol and becomes urea (many steps)
ornithine recycling
used to form citrulline (by combining with carbamoyl phosphate) but later generated by arginine (arginine makes urea + ornithine) in the cytosol so it goes back to mt to be reused
rate limiting enzyme for urea biosynthesis + what it does
CPS1 (carbamoyl phosphatase 1): CO2 + NH3 + ATP to make carbamoyl phosphate
consequence of CPS1 deficiency
ammonia (NH3) accumulates in liver, spills in other tissues. infant has severe symptoms (seizures, coma and very high blood NH3). low blood urea
consequence of a block of urea synthesis below the carbamoyl phosphate step (where CP CAN be synthesized)
high CP conc overloads CPS 2 (pyrimidine pathway in cytosol) and this creates a lot of orotic acid. (orotic aciduria) visible in the blood
how to detect site of block when see orotic aciduria
measure citrulline, arininosuccinate and arginine levels. (high levels = block is after that) low levels = block is before that
OTC deficiency conc of diff substrates (OTC = ornithine transcarbomyolase, enzyme to make citrulline)
high ammonia, high orotic acid, low citrulline
NOT HIGH CP bc converted to orotic acid
consequence of severe hepatocellular disease
less urea synthesis capability of the liver. the normal below 50 uM conc of urea in the blood can now exceed 1000uM.
must spread protein intake
cirrhosis def
disease of destruction of most hepatocytes + scarring leading to disorganization of pattern of blood flow to remaining hepatocytes
uremia and severe renal disease: what’s the link
severe renal disease = kidneys can’t excrete wastes. urea accum in the blood
why methionine can be toxic
has 1 catabolic pathway and if don’t elim methionine as fast as it gets in, excessive met conc can be toxic
rate limiting enzyme disease in metab of methionine and consequence
mutation of CBS enzyme. makes homocysteine into cystathionine.
blood: hyperhomocysteinemia
urine: homocystinuria
why get homocystinuria in CBS mutation
homocysteine is excreted as homocystine in the urine
name of the disease of CBS mutation
homocystinuria
vitamins required in normal methionine homeostasis
- B6 (pyridoxine) for CBS
2. folic acid (B9) and cobalamin (B12) for pathway making homocysteine back into met
most common serious disorder of aa metab
PKU (phenylketonuria)
PKU cause and problems
problem in Phe hydroxylase (makes Phe into Tyr)
Phe accum and damages the brain
PKU treatment and thing to be careful about
low but sufficient Phe
Tyr now essential aa
albinism cause
problem in enzyme tyrosinase which makes tyrosine into melanin (complex polymeric molecule)
alkaptonuria definition
disease of brown urine and cartilage damage due to homogentisic acid accumulation
why homogentisic acid accumulates in alkaptonuria
mutation in homogentisic acid oxidase (product: homogentisate is a metabolite in Phe and Tyr catabolism)
what’s cystine
disulfide bond molecule of 2 cysteines
cystinuria cause and consequence
impairment in tubular reabso of cysteine (and lysine, arginine, ornithine). cystine forms stones in the UT
how adaptation of diseases of substrate metabolism works
substrate accumulates and this increases rate of enzymes
overflow pathway def and examples
accum of metab upstream in a blocked pathway = these substrates go in another pathway not meant for them
ex:
- homocysteine forms homocystine which goes in urine
- orotic acid is form when carbamoyl phosphate accumulates
flow vs clearance
flow = rate of metabolic turnover (ex. 9g excreted per day) clearance = volume (of fluid cleared of that) per unit time clearance = metab turnover div. concentration
in a metab block disease, how are flow and clearance affected
flow (turnover is normal) but clearance is reduced bc conc increased (flow over conc is reduced, meaning clearance is reduced)
