Jan31 M1-Protein Metabolism in Health and Disease

Question 1

2 aa that are ntrs

Answer 1

glutamate and glycine

Question 2

how many different aa intracellularly and 2 special ones

Answer 2

21 including proline (imino acid) and selenocysteine

Question 3

N % of protein mass

Answer 3

16% (prots are 16% N)

Question 4

how to find amount of protein in a sample

Answer 4

get mass of N in it and multiply it by 6.25

Question 5

protein to total mass ratio in BCM and what occupies the rest of total mass

Answer 5

1:5. 200g protein for 1kg of BCM. water is the rest

1g protein for 4g water

Question 6

2 reasons dietary prot is essential

Answer 6

1. inefficient turnover (not all aa reused): obligatory N loss (some aa reduced for E)
2. aa abso and incorporation in endogenous prots is inefficient

Question 7

necessary and required daily prot

Answer 7

0. 65g per kg

0. 80 per kg

Question 8

what happens if eat too much protein

Answer 8

N balance stays 0. the excess aa are catabolized

Question 9

biologic value of a protein (food) and examples

Answer 9

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

Question 10

3 types of diseases where protein requirement is increased

Answer 10

• malabsorption
• protein loss
• protein-catabolic (ex. sepsis)

Question 11

what determines rate at which body is losing or gaining protein (practically)

Answer 11

N balance (Nin - Nout)

Question 12

how to estimate daily N excretion

Answer 12

urinary N + 4g (bc urinary N is 80% of N loss daily)

Question 13

how liver gets N for urea or temporary storage and why

Answer 13

through NEAAs interchanging their NH2 and become their corresponding ketoacid when they give it.
bc free N is highly toxic

Question 14

molecule of entry into urea cycle and how many NH2 in urea

Answer 14

glutamate.

urea has 2 NH2

Question 15

3 steps of urea synthesis

Answer 15

• 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)

Question 16

ornithine recycling

Answer 16

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

Question 17

rate limiting enzyme for urea biosynthesis + what it does

Answer 17

CPS1 (carbamoyl phosphatase 1): CO2 + NH3 + ATP to make carbamoyl phosphate

Question 18

consequence of CPS1 deficiency

Answer 18

ammonia (NH3) accumulates in liver, spills in other tissues. infant has severe symptoms (seizures, coma and very high blood NH3). low blood urea

Question 19

consequence of a block of urea synthesis below the carbamoyl phosphate step (where CP CAN be synthesized)

Answer 19

high CP conc overloads CPS 2 (pyrimidine pathway in cytosol) and this creates a lot of orotic acid. (orotic aciduria) visible in the blood

Question 20

how to detect site of block when see orotic aciduria

Answer 20

measure citrulline, arininosuccinate and arginine levels. (high levels = block is after that) low levels = block is before that

Question 21

OTC deficiency conc of diff substrates (OTC = ornithine transcarbomyolase, enzyme to make citrulline)

Answer 21

high ammonia, high orotic acid, low citrulline

NOT HIGH CP bc converted to orotic acid

Question 22

consequence of severe hepatocellular disease

Answer 22

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

Question 23

cirrhosis def

Answer 23

disease of destruction of most hepatocytes + scarring leading to disorganization of pattern of blood flow to remaining hepatocytes

Question 24

uremia and severe renal disease: what’s the link

Answer 24

severe renal disease = kidneys can’t excrete wastes. urea accum in the blood

Question 25

why methionine can be toxic

Answer 25

has 1 catabolic pathway and if don’t elim methionine as fast as it gets in, excessive met conc can be toxic

Question 26

rate limiting enzyme disease in metab of methionine and consequence

Answer 26

mutation of CBS enzyme. makes homocysteine into cystathionine.

blood: hyperhomocysteinemia
urine: homocystinuria

Question 27

why get homocystinuria in CBS mutation

Answer 27

homocysteine is excreted as homocystine in the urine

Question 28

name of the disease of CBS mutation

Answer 28

homocystinuria

Question 29

vitamins required in normal methionine homeostasis

Answer 29

1. B6 (pyridoxine) for CBS

2. folic acid (B9) and cobalamin (B12) for pathway making homocysteine back into met

Question 30

most common serious disorder of aa metab

Answer 30

PKU (phenylketonuria)

Question 31

PKU cause and problems

Answer 31

problem in Phe hydroxylase (makes Phe into Tyr)

Phe accum and damages the brain

Question 32

PKU treatment and thing to be careful about

Answer 32

low but sufficient Phe

Tyr now essential aa

Question 33

albinism cause

Answer 33

problem in enzyme tyrosinase which makes tyrosine into melanin (complex polymeric molecule)

Question 34

alkaptonuria definition

Answer 34

disease of brown urine and cartilage damage due to homogentisic acid accumulation

Question 35

why homogentisic acid accumulates in alkaptonuria

Answer 35

mutation in homogentisic acid oxidase (product: homogentisate is a metabolite in Phe and Tyr catabolism)

Question 36

what’s cystine

Answer 36

disulfide bond molecule of 2 cysteines

Question 37

cystinuria cause and consequence

Answer 37

impairment in tubular reabso of cysteine (and lysine, arginine, ornithine). cystine forms stones in the UT

Question 38

how adaptation of diseases of substrate metabolism works

Answer 38

substrate accumulates and this increases rate of enzymes

Question 39

overflow pathway def and examples

Answer 39

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

Question 40

flow vs clearance

Answer 40

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

Question 41

in a metab block disease, how are flow and clearance affected

Answer 41

flow (turnover is normal) but clearance is reduced bc conc increased (flow over conc is reduced, meaning clearance is reduced)