Amino Acid Degradation - Lec. 32 Flashcards
make you cry
what do the twenty amino acids have in common in terms on their function?
they can all provide energy and they can all be used to synthesize either glucose or ketone bodies
what 5 amino acids can used for both glucose and ketone bodies?
- phenylalanine (aromatic a.a.)
- isoleucine
- tryptophan (aromatic a.a.)
- threonine
- tyrosine (aromatic a.a.)
what amino acids can only produce ketone bodies?
- lysine
- leucine
what is transamination?
mechanism that transfers aminium between alpha amino acid and alpha keto acid
what are the key amino acids that play a critical role in nitrogen metabolism? (HINT: GAA there’s 3)
- glutamate
- aspartate
- alanine
what are the corresponding alpha keto acids for the following alpha amino acids:
- alanine
- aspartate
- glutamate
- alanine = pyruvate
- aspartate = oxaloacetate
- glutamate = alpha- ketoglutarate
all three of these amino acids are glucogenic because they can be used for gluconeogenesis (form new glucose molecules)
what is the key chemical that can redirect the TCA cycle into phosphoenolpyruvate?
oxaloacetate
how are glutamate and proline similar?
they’re chemical make up is the same, but their structures differ in the sense of their side chains –> prolines side chain loops back up while glutamate is just a side chain with no loop
examples of transamination - what amino acids go through transamination to produce the following amino acids?
- aspartate
- glutamate (two amino acids)
- asparagine goes through transamination to form aspartate
- glutamine goes through transamination to form glutamate as well as proline
how many entry points are there for the TCA cycle? What are they?
there are a total of seven entry points
- oxaloacetate
- alpha-ketoglutarate
- succinyl-CoA
- fumarate
- pyruvate
- acetyl-CoA
- acetoacetate
what are the two entry points of the TCA cycle that are also used in the amino acid degradation into ketone body pathway?
- acetyl-CoA
- acetoacetate (the combining of two acetyl-CoA)
of the 7 ketogenic amino acids, what are the three that have aromatic rings?
- phenylalanine
- tyrosine
- tryptophan
- these are going to be both ketogenic and glucogenic because the ring structure has a part that will synthesize ketone bodies and another part of the ring to synthesize glucose
why is threonine considered ketogenic and glucogenic?
threonine can break down into glycine and acetyl-CoA
- the acetyl-CoA can be used to synthesize ketone bodies, making it ketogenic
- glycine is used to synthesize glucose
why is acetyl-CoA not considered a glucogenic amino acid?
acetyl-CoA is only acting as a fuel source for the TCA cycle which will be broken down to produce that fuel source, thus it’s ultimately not going to be used towards the structure of the glucose molecule at the end
glyoxylate cycle
this is a cycle utilized to produce glucose using acetyl-CoA but humans do not use this cycle as our biological makeup does not use acetyl-CoA towards the structure of glucose - acetyl-CoA instead gets broken down for energy to power the TCA cycle
what is purpose of cofactors for amino acid metabolism, degradation and synthesis?
these are important for transferring a carbon from and to molecules
- cofactors are groups of chemicals that involve a single carbon transfer
what are examples of single carbon molecules?
-COO-
-CHO
-CH2O-
-CH3
COO- is the most oxidized
CH3 is the most reduced
biotin cofactor
biotin can transfer CO2
- biotin functions as a cofactor that aids in the transfer of CO2 groups to various target macromolecules
SAM (S-adenosylmethionine cofactor)
transfers CH3 (most reduced single carbon) - plays a critical role in the transfer of methyl groups to various biomolecules, including DNA, proteins and small-molecule secondary metabolites
THF (tetrahydrofolate) cofactor
can do multiple jobs - transfer the different types of single carbon molecules (CHO, CH2O, CH3)
an example of how biotin cofactor is used is TCA cycle
converting pyruvate to oxaloacetate is done by an enzyme called pyruvate carboxylase and the biotin cofactor will work with the enzyme and transfer CO2 to oxaloacetate
why is THF so useful in regards to single carbon transfer
allows single carbon molecules to be converted within the molecule itself in the presence of the right enzyme required and the THF cofactor
ex. CH3 to CH2OH (methyl to methylene)
what is the importance of SAM cofactor (single carbon transfer)
it is the key/main methyl group carrier in cells - has a much higher affinity to methyl group then compared to THF
–> function of the SAM and the methyl group is important in many ways
mechanism of amino acid degradation of asparagine (Asn) and aspartate (Asp) to oxaloacetate
asparagine has an additional amino group that will be removed from the enzyme asparaginase to form aspartate and from aspartate an enzyme called aspartate aminotransferase (AST), converts the aspartate to oxaloacetate
asparaginase enzyme
converts asparagine to aspartate by removing an amino group (NH4+)
aspartate aminotransferase (AST) enzyme
this enzyme will convert aspartate to oxaloacetate through transamination using the PLP cofactor
- this enzyme is highly expressed in the liver
what key enzyme is liver specific that converts aspartate to oxaloacetate
aspartate aminotransferase (AST) - once this enzyme produces oxaloacetate the oxaloacetate will be used to produce phosphoenolpyruvate and then ultimately glucose -->liver specific pathway
why then are asparagine and aspartate glucogenic amino acids?
asparagine will convert to aspartate through the enzyme asparaginase and then aspartate will be converted to oxaloacetate by the enzyme aspartate aminotransferase (transamination and PLP cofactor used) –> thus since oxaloacetate is used to produce glucose, both asparagine and aspartate are considered glucogenic amino acids due to their role in gluconeogenesis
glutaminase enzyme
converts glutamine to glutamate by removing amino group
glutamate dehydrogenase enzyme
converts glutamate to alpha-ketoglutarate through transamination
- this enzyme can convert both glutamate to alpha-ketoglutarate and reverse it back, from alpha-ketoglutarate to glutamate
arginase enzyme
converts arginine to ornithine and removes a urea molecule –> this is a part of the urea cycle and also the last step of the urea cycle
what five amino acids can eventually convert to form alpha-ketoglutarate?
what do they all have in common?
- glutamine
- arginine
- proline
- histidine
- glutamate
- these all have a continuous 5 carbon chain
what are the six amino acids that can be converted into pyruvate?
- alanine
- cystine
- glycine
- serine
- threonine
- tryptophan
why are serine and cystine typically coupled together?
the can convert back and forth with one another
of the six amino acids that are used to produce pyruvate what ones have an aromatic ring? what is the significance or aromatic rings?
- tryptophan and threonine
- the aromatic ring allows these two amino acids to do both glucogenic and ketogenic
what does threonine break down into to make it both ketogenic and glucogenic?
threonine can break down into acetyl-CoA and glycine and the acetyl-CoA is used during gluconeogenesis for production of glucose molecules
why is tryptophan considered both glucogenic and ketogenic?
since it is an aromitic ring structure there are parts of the ring that is designated to glucose synthesis and another part of the ring for ketone bodies; when tryptophan breaks down its converted to alanine which converts ultimately to pyruvate (pyruvate is a substrate for gluconeogenesis)
what are the three amino acids that can undergo branched amino acid degradation?
- leucine
- isoleucine
- valine
mechanism of degradation of branched-chain amino acids
first step is transamination of the removal of amino group to convert them into alpha keto acids by branched-chain aminotransferase enzyme
then they are processed by a special protein complex called alpha-keto acid dehydrogenase complex (BCKDH) to produce the amino acid acyl-CoA derivatives
what does the enzyme branched-amino transferase do? what amino acids utilize this enzyme?
this enzyme converts the alpha amino acids into their alpha keto acid forms (removes amino group and produces ketone)
- the amino acids that utilize this enzyme are:
- valine
- isoleucine
- leucine
what does the alpha-keto acid dehydrogenase complex do?
this is a special protein complex enzyme that converts alpha keto acids into their acyl-CoA derivatives by putting on an acyl-CoA to the side chain
what cause maple syrup urine disease?
having a defect in the alpha-keto acid dehydrogenase complex will result in the complex not functioning properly by not breaking down the branched-chain aminotransferase
what 4 amino acids form into succinyl-CoA
- isoleucine
- valine
- threonine
- methionine
what makes isoleucine ketogenic and glucogenic
when isoleucine breaks down it forms an acetyl-CoA (forms ketone body) and propionyl-CoA which will ultimately form glucose
how is threonine both ketogenic and glucogenic
threonine can be degraded in multiple ways; one way is to produce succinyl-CoA which is ketogenic pathway; and the other pathway is by ultimately forming pyruvate which will produce glucose (glucogenic pathway)
what are the 7 ketogenic amino acids
- tryptophan
- lysine
- phenylalanine
- leucine
- tyrosine
- isoleucine
- threonine
amino acids are the building blocks for many important biological molecules, such as
- tryptophan can be used a neurotransmitter
- glutamate can be used to form GABA
- histidine can be used to form histamine for our allergic reactions
