AA Catabolism
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Essential vs Non-Essential AAs
Essential AAs = Amino acids we CANNOT synthesize on our own; we must acquire them from our diet (= are an “essential” part of our diet) Non-Essential AAs = Amino acids we CAN synthesize on our own (= are a “non-essential” part of our diet, we don’t need to get them from our food)
List the Essential AAs:
There are 9 essential AAs: 1) Tryptophan 2) Threonine 3) Histidine 4) Valine 5) Isoleucine 6) Phenylalanine 7) Methionine 8) Leucine 9) Lysine
What is the pneumonic for the essential AAs?
Try THis VIP MaLL (Careful!! P = Phenylalanine!)
List the Non-Essential AAs:
There are 11 non-essential AAs: 1) Alanine 2) Arginine 3) Aspartate 4) Asparagine 5) Cysteine 6) Glycine 7) Glutamine 8) Glutamate 9) Proline 10) Serine 11) Tyrosine (All those NOT in “Try THis VIP MaLL”
Carbon skeletons of AAs have what two main fates in AA catabolism?
1) Entry into the ketone body pathway (conversion to acetyl-coA) 2) Entry into the TCA cycle (conversion to TCA intermediate)
What are glucogenic vs ketogenic AAs?
Ketogenic AAs = Amino acids whose carbon skeletons can be converted into acetyl-CoA or acetoacetyl-CoA to then enter ketone body production pathways Glucogenic AAs = Amino acids whose carbon skeletons can be converted into TCA cycle intermediates to continue into the TCA cycle to make OAA and enter gluconeogenesis!
How many AAs are glucogenic vs ketogenic?
Ketogenic = Total SEVEN (2 solely, 5 mixed) Glucogenic = Total EIGHTEEN (13 solely, 5 mixed) –> 2 AAs are ONLY ketogenic –> 13 AAs are ONLY glucogenic –> 5 AAs are BOTH ketogenic + glucogenic
List the solely glucogenic AAs
13 of them: 1) Alanine 2) Arginine 3) Asparagine 4) Aspartate 5) Cysteine 6) Glycine 7) Glutamine 8) Glutamate 9) Histidine 10) Methionine 11) Proline 12) Serine 13) Valine
List the solely ketogenic AAs
2 of them: 1) Lysine 2) Leucine (The 2 Ls!)
List the AAs that are BOTH ketogenic and glucogenic:
“These don’t FITTT in either category” (5 of them) 1) Phenylalanine (F) 2) Isoleucine (I) 3) Tyrosine (T) 4) Threonine (T) 5) Tryptophan (T)
What are the 4 critical cofactors used in enzymes in AA catabolism?
1) PLP = Transamination rxns 1 Carbon transfer rxns: 2) Biotin 3) adoMet (adenosylmethionine) 4) THF (Tetrahydrofolate)
What are the cofactors mainly used in 1 carbon transfer rxns?
Biotin, adoMet, THF
What is Biotin derived from?
Vitamin B7 (biotin)
What oxidation state is the carbon that biotin can transfer?
Solely CO2! = most oxidized form of carbon!
Explain the process of biotin-mediated carbon transfer:
1) Biotin binds to carboxylase enzyme active site via a lysine residue that forms an amide linkage with biotin’s long COO- arm! 2) Once anchored, the carboxylase enzyme phosphorylates bicarb using ATP to activate it 3) Once activated, one of biotin’s nitrogens attacks the bicarb, displacing the Pi grp and forming a bond with CO2! 4) The biotin typically then swings over to the oppositve active site and donates this CO2 group to a substrate that comes in! (carboxylating the substrate)
In the biotin catalytic mechanism, what are the two activities of the enzyme bound to biotin?
1) Biotin carboxylase = Carboxylates the biotin itself (adds CO2) 2) Carboxyl transferase = Transfers CO2 grp from biotin to substrate
What is THF derived from?
Vitamin B9 (folate)
What oxidative states of carbon can THF transfer?
1) Methyl (-CH3) 2) Methylene (-CH2-) (-CH2OH) 3) Methenyl (-CH=) (-CH=O)
On THF, where are the 1 carbon grps bound to?
Bound to either: 1) N5 2) N10 3) N5 AND N10 (N5, N10)
Where does the carbon usually come from when THF gain a carbon to transfer?
Typically comes from SERINE! (CAN also come from glycine or formate)
What is adoMet derived from?
Adenosine + methionine
What is the oxidation state of the carbon that can be transferred with adoMet?
METHYL (only methyl!)
Which carbon in adoMet gets transferred?
The methyl grp coming off of the suflur from methionine
What other cofactor is involved in the regeneration (remethylation) of adoMet?
N5-methyl-THF! (only known use for this cofactor actually!)