Protein Metabolism (mini-test 2) Flashcards
What percent of our bodies energy comes from AA oxidation?
10-15% (even more if starving)
Amino acids undergo oxidative degradation under 3 different situations. What are they?
1) normal recycling of cellular proteins
2) protein rich diet (AAs cannot be stored)
3) during starvation or in uncontrolled DM, AAs are used for fuel (ATP production) or for gluconeogenesis
Dietary proteins are absorbed during….
Digestion
What are the 2 instances of tissue proteins getting degraded?
1) proteins are old
2) starvation
What enzyme is used to synthesize tissue proteins from AAs?
Peptidotransferase
Which AAs can be synthesized by the body?
The 10 nonessential AAs
Eating lots of dietary proteins will help build muscle if the person exercises and has physical demands, but if not, then the body will break down the protein through deamination rather than becoming tissue protein. So this will generate lots of urea and can turn to ATP, but if ATP is enough then it will change to….
Fat
What makes up a general AA?
Amino group, R group, carboxyl group, H, and alpha carbon
What is transamination?
Transfer of amino group from AA to an alpha keto acid
What is deamination?
Removal of amino group from AA, which creates alpha keto acid and the amino group becomes ammonia
Why are AAs not the preferred energy source?
Bc breaking down AAs creates ammonia which is a toxic compound and can only be processed in the liver
Ammonia is a converted to what in the liver to be excreted through kidneys in the urine?
Urea
Alpha keto acids will be used to build up what 3 things?
1) glucose (through gluconeogenesis)
2) make ATP in TCA
3) ketone bodies (fasting state)
AAs within the AA pool can undergo decarboxylation. What is this?
Carboxyl group of AA is removed and the AA is now known as an amine
Ex: glutamate is a neurotransmitter activator and after decarboxylation it becomes GABA which is an amine
AAs within the AA pool of the body can become biologically active compounds like….
Neurotransmitters and hormones
Deamination is done with what enzyme?
Glutamate dehydrogenase
Removing the amine group of an AA is called….
Deamination
Where does deamination occur?
In the liver
T/F: any tissue besides the liver cannot do deamination
TRUE, so muscles and other tissues only do transamination
Does transamination synthesize ammonia?
NO
Is transamination reversible or irreversible?
Reversible
Which AA cannot be transaminated?
Lysine
ALL aminotransferases use a coenzyme. What is it and what is it derived from?
Pyridoxal phosphate, which is derived from, vit B6
What are the 3 aminotransferase pairs we should know?
1) alpha KG and glutamate
2) pyruvate and alanine
3) aspartate and OAA
If alanine donates NH2 to alpha KG what enzyme is used and what are the products?
Enzyme= glutamate pyruvate aminotransferase (GPT) OR alanine aminotransferase (ALT)
Products= pyruvate and glutamate
What vitamin is required with ALT, AST, GPT, or GOT?
Vit B6
If aspartate donates NH2 to alpha KG, what enzyme is used and what are the products?
Enzyme= glutamate OAA aminotransferase (GOT) or aspartate aminotransferase (AST)
Products= OAA and glutamate
The alanine cycle begins in the muscles with pyruvate. Pyruvate will undergo transamination and become what?
alanine
The alanine cycle begins in the muscles with pyruvate. Pyruvate will undergo transamination and become alanine. Alanine will be transported out of the muscle to blood and then to the liver. From here, alanine will convert back to pyruvate, while an alpha KG can undergo transamination here at the same time and make glutamate. Glutamate is the collecting point. Glutamate will undergo deamination to make ammonia and urea with what enzyme?
glutamate DH
In muscle tissues, alpha KG can undergo transamination and become glutamate. Glutamate is too acidic to be transported in the blood so it first has to convert to glutamine. What enzyme does this?
glutamine synthetase
In muscle tissues, alpha KG can undergo transamination and become glutamate. Glutamate is too acidic to be transported in the blood so it first has to convert to glutamine. From here glutamine will be transported out of the muscles to blood and then to liver. Glutamine will then change back to glutamate (collecting point) + NH3 with what enzyme?
glutaminase
What 2 AAs can be transported in the blood and are the major transport form of NH3?
alanine and glutamine
When is the alanine cycle most active?
starvation
Glutamate and ammonia undergo a reaction with glutamine synthetase to make glutamine. What does it require?
2 ATP
Glutamate is the collecting point of….
ALL amine groups removed from AAs
Deamination is what type of reaction?
oxidative deamination reaction
What does glutamate use to make alpha KG with glutamate DH?
NAD+ or NADP+
Urea is a _____________ waste product
nitrogenous
Urea is generated in the urea cycle. Where is the urea cycle?
mitochondria and cytosol of liver
Urea cycle occurs in the mitochondria and cytoplasm of the liver. What is the only other pathway that is here?
gluconeogenesis
Where do the 2 nitrogens come from in urea?
1) oxidative deamination of glutamate
2) aspartate
Where does the carbon come from in urea?
from the CO2 that was generated in TCA
In the urea cycle, step 1 is in the mitochondria and this is where NH4+ and CO2 combine with __________________________________ to generate carbomoyl phosphate
carbamoyl phosphate synthetase I (CPS1)
note: 2 ATP is required for this step
What is the RLE in the urea cycle?
carbamoyl phosphate synthetase I (CPS1)
What is the rate limiting step in the urea cycle?
step 1
What 2 urea cycle enzymes are in the mitochondria?
1) carbamoyl phosphate synthetase I (CPS1)
2) ornithine transcarbamoylase (OTC)
In the urea cycle, step 2 is still in the mitochondria. Ornithine is combined with carbamoyl phosphate by ________________________________ to generate citrulline. Citrulline is then transported into the cytoplasm of the liver
ornithine transcarbamoylase (OTC)
What are 2 nonstandard AAs that are also VIP molecules in the urea cycle?
1) ornithine (smaller)
2) carbamoyl phosphate (larger)
In step 3 of the urea cycle, it is now in the cytoplasm. Citrulline is condensed with aspartate by ______________________________ to create argininosuccinate.
argininosuccinate synthetase
note: 2 ATP are required here and the hydrolysis of ATP to AMP DRIVES THIS RXN
What are the 3 basic AAs?
1) lysine
2) arginine
3) histidine
In step 4 of the urea cycle, ______________________ cleaves argininosuccinate to form fumarate (which can enter the TCA cycle) and arginine
argininosuccinate lyase
In step 5 of the urea cycle, _______________ cleaves arginine to release urea and regenerate ornithine. Ornithine re-enters the mitochondria for further urea cycle rounds. Urea passes into the blood and is excreted by the kidneys
arginase
How many ATPs are required for 1 round of urea cycle?
4
What 2 enzymes in urea cycle require 2 ATP (4 in total with both enzymes)?
1) carbamoyl phosphate synthetase I (CPS1)
2) argininosuccinate synthetase (ASS)
T/F: the body does not like using AAs for energy
true
What 2 organs have to work hard bc of urea cycle?
liver and kidneys
What does BUN stand for?
blood urea nitrogen
What does increased BUN indicate?
kidney dysfunction (kidneys are unable to excrete waste products)
What markers indicate liver damage (cannot form urea)?
1) increased ALT or AST
2) decreased BUN
What are the 10 essential AAs?
-phenylalanine
-valine
-threonine
-tryptophan
-isoleucine
-methionine
-histidine
-arginine
-leucine
-lysine
PVT TIM HALL
note: this is only in a positive nitrogen balance (growth in kids or pregnant moms, recovery after injury or surgery, etc)
Otherwise there are 8 essential AAs (his and arg are conditionally essential)
Which 8 AAs are essential all the time?
-phenylalanine
-valine
-threonine
-tryptophan
-isoleucine
-methionine
-leucine
-lysine
Which 2 AAs are conditionally essential, only during positive nitrogen balance?
histidine and arginine
What is the allosteric activator for carbamoyl phosphate synthetase I (CPS1) in step 1 of urea cycle?
N-acetylglutamate (it indicates a buildup of glutamate and amino groups, so its time to make urea)
AAs can be glucogenic, ketogenic, or both. What is the fate of the carbon skeletons for glucogenic AAs?
will become glycolytic or TCA cycle intermediates
AAs can be glucogenic, ketogenic, or both. What is the fate of the carbon skeletons for ketogenic AAs?
will become acetyl CoA or acetoacetate
18 of the standard AAs are glucogenic, and 2 are ketogenic. Which 2 AAs are ketogenic?
leucine and lysine (so these are the only 2 standard AAs that CANNOT change to glucose)
18 of the standard AAs are glucogenic, and 2 are ketogenic. BUT, 4 are both ketogenic and glucogenic. What are these 4 AAs?
1) tyrosine
2) isoleucine
3) phenylalanine
4) tryptophan
PITT
What are the 3 branch chain AAs (BCAAs)?
1) valine
2) leucine
3) isoleucine
What 2 BCAAs can change to glucose?
valine and isoleucine
Which 2 BCAAs can change to ketone bodies?
leucine and isoleucine
Ala carbon skeleton will be converted to…
pyruvate
Arginine carbon skeleton will be converted to…
alpha KG
Asparagine carbon skeleton will be converted to….
aspartate and then OAA
Cysteine carbon skeleton will be converted to…
pyruvate
Glutamine carbon skeleton will be converted to…
glutamate and then alpha KG
Glycine carbon skeleton will be converted to…
pyruvate
Proline carbon skeleton will be converted to…
alpha KG
Histidine carbon skeleton will be converted to…
alpha KG
Methionine carbon skeleton will be converted to…
SCoA or
homocysteine which can then be converted to cysteine and then back to methionine
Threonine carbon skeleton will be converted to…
SCoA
Valine carbon skeleton will be converted to…
SCoA
Isoleucine carbon skeleton will be converted to…
SCoA
Phenylalanine carbon skeleton will be converted to…
tyrosine and then fumarate
What enzyme converts phenylalanine to tyrosine?
phenylalanine hydroxylase
Tryptophan carbon skeleton will be converted to…
pyruvate
Serine carbon skeleton will be converted to…
pyruvate
or
cystiene
or
glycine and then heme or collagen
AAs can change to what 4 TCA intermediates?
SOFA
1) succinyl CoA (SCoA)
2) OAA
3) fumarate
4) alpha KG
and some AAs can change to pyruvate
Asparagine (Asn) will be converted to aspartate. Aspartate (Asp) and alpha KG will undergo reaction with _______ to make OAA
AST
What 2 AAs can make OAA?
Asn and Asp
What 2 AAs can make fumarate?
Phe and Tyr
What coenzyme is required to convert Phe to Tyr?
biopterin/ tetrahydrobiopterin (produced by humans from GTP)
When Phe converts to Tyr and then to Fumarate, what is also made with fumarate?
acetoacetate
What is PKU (phenyloketonuria)?
in normal situations phe should be able to convert to tyr but here patients are:
-deficient in phe hydroxylase
-causes mental retardation and odor in urine
-need to restrict phe intake
-need to completely avoid artificial sweeteners like aspartame because its asp + phe
-tyrosine is essential here
What does tyrosine synthesize?
-pigment
-catecholamines
-thyroid hormones
What enzyme converts tyrosine to melanin?
tyrosinase
What is albinism?
-tyrosine cannot convert to melanin because theres a tyrosinase deficiency
-causes lack of pigmentation in the eyes, skin, and hair
Tyrosine can be converted to homogentistate. Homogentistate can then be converted to fumarate with what enzyme?
homogentistate oxidase
What is alcaptonuria?
in normal cases, Tyrosine can be converted to homogentistate. Homogentistate can then be converted to fumarate with homogentistate oxidase
but here, the enzyme is deficient so there will be an accumulation of homogentistate
this causes:
-black urine and bone disease
-joint pain, organ damage, kidney stones
tx:
-vit C supplementation
-restrict phe and tyr
What are the 3 aromatic AA metabolic diseases?
1) PKU
2) albinism
3) alcaptonuria
What 4 AAs can make succinyl CoA?
VITM
1) valine
2) isoleucine
3) threonine
4) methionine
these AAs go through VOMIT pathway- all the letters match up to AA, but O stands for odd chain FA bc the AAs will be broken down to propionyl CoA
There are 4 AAs that can make succinyl CoA: valine, isoleucine, threonine, and methionine. This is the VOMIT pathway. They are first broken down to propionyl CoA and then are converted to methylmalonyl CoA with ___________________________. Methylmalonyl CoA is then converted to succinyl CoA with ____________________________
propionyl CoA carboxylase and ABC, methylmalonyl CoA mutase and vit B12
note: this is the exact same reactions that happens with odd chain FAs
What vitamins are required to convert VITM (valine, isoleucine, threonine, and methionine) into succinyl CoA?
vit B7 (biotin) and B12
Valine and isoleucine are BCAAs. After transamination, they become branch chain ketoacids. This can be further broken down with branch chain ketoacid DH. The products are then used to generate propionyl CoA. What coenzymes are required for branch chain ketoacid DH?
TLCFN
(same coenzymes that are required by pyruvate DH)
Maple syrup urine disease is characterized by….
branch chain ketoacid DH deficiency
Does leucine produce succinyl CoA?
NO
What 2 AAs contain sulfur?
methionine and cysteine
Methionine can be converted to S-adenosylmethionine (SAM) which is a….
carbon donor
methionine can be converted to homo__________
cysteine
What is maple syrup urine disease? What is the treatment?
-caused by branch chain alpha keto acid DH deficency
-causes ketoacids to build up in the urine which gives it a maple syrup smell
tx:
-strict diet with restricted protein but high carb
-thiamine supplements
What is homocysteinemia? What is the treatment?
-increase of homocysteine in the blood
-associated with neuro and cardiovascular diseases
-could be due to enzyme deficiency (rare)
-usually due to vitamin deficiency with vit B6, B9 (folic acid), or B12
tx:
-restrict methionine intake
-vit B6, B9, and B12 supplements
inadequate B12 and B9 (folate) may cause _____________ deficiency
methionine
Met gets converted to SAM. SAM is a modified met and it donates methyl group to DNA. SAM is then converted to homocysteine. At this point homocysteine can convert back to methionine if theres adequate levels of….
vit B12 and B9 (folate)
Met gets converted to SAM. SAM is a modified met and it donates methyl group to DNA. SAM is then converted to homocysteine. At this point homocysteine can convert back to methionine if theres adequate levels of vit B12 and B9 (folate). Another option is- homocysteine can make LDL (bad cholesterol). Or another option is homocysteine can be converted to cysteine and propionyl CoA (which will then be converted to succinyl CoA) if theres adequate….
serine and vit B6
What are the 5 AAs that can make alpha KG?
PHAGG
1) proline (cyclic)
2) histidine (basic)
3) arginine (basic)
4) glutamine (neutral)
5) glutamate (acidic)
What 5 AAs can make pyruvate?
G CAST
1) glycine
2) cysteine
3) alanine
4) serine
5) tryptophan
note: serine, glycine and cysteine are non-essential BUT they are very important for our health
-serine can be converted to cysteine and glycine
-glycine is needed to make collagen for bones, skin, hair and glycine also makes heme (not enough gly= can result in anemia)
-cysteine is an antioxidant bc of the thiol group
Which enzyme is used with vit B6 and 9 to catalyze a reversible conversion of serine to glycine?
serine hydoxymethyl transferase
Tryptophan is the largest AA and in order to make pyruvate, it is cleaved to liberate alanine and _________ group/ring
indole
What are the products of catabolsim for ketogenic AAs?
acetoacetate or acetyl CoA
acetyl CoA can be used in TCA
note: only leucine and lysine are exclusively ketogenic
Do ketogenic AAs use pyruvate as an intermediate?
no
