Purine Metabolism - Lec. 33 Flashcards
make you wonder if this is going to ever end
what two amino acids are the critical regulators of nitrogen (or amino acids) synthesis in our cells?
glutamate and glutamine
- they serve as a sensor of nitrogen levels in cells
glutamine synthetase
converting glutamate into glutamine by consuming a molecule of ATP and ammonia
- it is allosterically regulated
how is glutamine made?
glutamine is made through a molecule of glutamate and an enzyme called glutamine synthetase
- glutamine synthetase is a regulator and what converts glutamate to glutamine
- its an allosteric regulator which is regulated by the binding of an effector molecule on the site other than its enzymatic active site
what is glutamine capable of regulating? (what biomolecules)
- AMP
- CTP
- tryptophan
- histidine
- carbamoyl phosphate
what does carbamoyl phosphate do?
this is the molecule that will integrate a nitrogen into the urea cycle by combining with a molecule of ornithine to ultimately form a molecule of citrulline that will pass into the cytoplasm of the liver cell
how is glutamine synthetase allosterically regulated?
it is allosterically regulated by a number of amino acids like AMP, CTP, histidine, tryptophan, carbamoyl phosphate, glycine, alanine, and glucosamine 6-phosphate
- all of these are allosteric inhibitors of glutamine synthetase (the enzyme that converts glutamate to glutamine) –> so when any of these inhibitors reach a level too high it will inhibit the enzyme and slow it down or stop it so that it does not produce any more substrates
- they can also be thought of as overall “indicators” that tell our cells we have enough glutamine around so we do not need to produce any more and they inhibit that enzyme (glutamine synthetase) to prevent the formation of any more glutamine
allosteric regulation
an enzyme is regulated by binding an effector molecule on a site other than its enzymatic site of the actual enzyme (so it can be inhibited and turned off ultimately)
how is glutamine formed? (what enzyme)
glutamine is formed through a molecule of glutamate that is converted by the enzyme glutamine synthetase –> glutamine synthetase is allosterically regulated
how is glutamate formed in bacteria and plants? (by what enzyme)
glutamate is formed through the enzyme glutamate synthase (different than glutamate synthetase - which converts glutamate to glutamine)
glutamate synthase enzyme
takes a molecule of glutamine and transfers an amino group to a molecule of alpha-ketoglutarate to form two molecules of glutamate but this will only occur in bacteria and plants
how do humans form glutamate? (two different mechanisms)
for humans we use a molecule of alpha-ketoglutarate and ammonia to form glutamate, and the enzyme responsible is glutamate dehydrogenase
OR transfers an amino group from an alpha-amino acid to a molecule of alpha-ketoglutarate which forms the glutamate and an alpha-keto acid (from the alpha-amino acid that lost the amino group)
- **remember that glutamate dehydrogenase is one of three enzymes that can integrate a free ammonia
essential amino acids
means that the amino acid cannot be synthetized by most mamamilian cells and it needs to be obtained through dietary proteins/foods we eat
essential amino acids (9) - name them
- phenylalanine
- valine
- tryptophan
- threonine
- isoleucine
- methionine
- histidine
- leucine
- lysine
nonessential amino acids (5) - name them
- alanine
- asparagine
- aspartate
- glutamate
- serine
nonessential amino acids
nonessential amino acids means that those ones can be easily synthesized in our cells from other metabolite (nonessential and conditionally essential)
conditionally essential amino acids (6) - name them
- arginine
- cysteine
- glutamine
- glycine
- proline
- tyrosine
3 critical amino acids for the TCA cycle? HINT: GAA
- glutamate –> can be converted to alpha-ketoglutarate
- aspartate –> can be converted to oxaloacetate
- alanine –> can be converted to pyruvate
what are the critical regulators of amino acid synthesis or nitrogen metabolism (urea cycle)?
- glutamate
- glutamine
where does the amino group for amino acid synthesis come from? (what two amino acids)
- glutamine
- glutamate
amino acid synthesis
- the source of the amino group for amino acid biosynthesis comes from glutamine or glutamate
- amino acids can be derived from intermediates like
- glycolysis
- TCA cycle (citric acid cycle)
- Pentose phosphate pathway
what amino acids can form from a molecule of glutarate?
- glutamine
- proline
- arginine through
through transamination what will form from a molecule of alpha-ketoglutarate (if it combines with an amino group)
alpha-ketoglutarate can combine with an alpha-amino acid which will form an alpha- keto acid (from the alpha-amino acid losing its amino group) and a molecule a glutamate will form
what is arginine synthesized from? (think back to beginning of urea cycle)
arginine is synthesized from ornithine
- glutamate will be involved as glutamate will ultimately convert to ornithine which will get fed into the urea cycle and break down into arginine through a series of processes (arginine will break down into ornithine and urea through the enzyme arginase)
how to do humans synthesize proline from ornithine?
ornithine will undergo transamination through a molecule of alpha-ketoglutarate and an alpha amino-acid, ornithine, using the enzyme called ornithine gamma-aminotransferase, which in turn will produce a glutamate thats converted to PSC and then ultimately the final product of proline
how does serine derive from 3PG (3-phosphoglycerate)?
serine derives from 3PG through two different enzymatic process by undergoing oxidation and then transamination and lastly dephosphorization to produce serine
in reference to serine, what other amino acids usually group together with it?
serine is typically coupled with glycine and cysteine
how is cysteine synthesized from homocysteine and serine?
homocysteine is derived from the SAM cycle that uses a molecule of methionine, which has a sulfur molecule attached to it (we need a sulfur atom for the final product of cysteine), and the SAM cycle eventually produces homocysteine (which has that sulfur attached) and it will combine with a molecule of serine to ultimately produce cysteine as the product as well as an alpha-ketoglutarate
where does the sulfur come from during the synthesis of cysteine from serine and homocysteine?
cysteine has a sulfur within in its side chain which will ultimately come from the SAM cycle that induces methionine degradation (keep in mind methionine has a sulfur attached) that in turn will produce a molecule of homocysteine, that has the sulfur molecule attached, and thus together the homocysteine and serine will combine together and produce a molecule of cysteine
what does oxaloacetate produce through transamination (addition of an amino group)
through transamination oxaloacetate (OAA) will convert to aspartate by adding an amino group
once oxaloacetate produces a molecule of aspartate through transamination (adding an amino group) what can aspartate produce? (what 4 amino acids can be synthesized)
- asparagine through transamination (add amino group)
- methionine
- lysine
- threonine –> threonine can also be further converted into isoleucine
what are the amino acids which are synthesized through pyruvate? (mnemonic: pyruvate (I)s (A)ll (V)ery (L)eucy
- alanine
- valine
- leucine
- isoleucine
what are the branched amino acids that can undergo branched amino acid degradation? (LIV –>they call come from pyruvate)
valine leucine isoleucine *** these all come from pyruvate * know this
does isoleucine have an amino transferase enzyme?
no. isoleucine instead uses the valine aminotransferase alpha-ketoglutarate enzyme to convert the ketone to an amino group
what is the name of the aminotransferase used for valine and leucine?
valine uses the valine aminotransferase alpha-ketoglutarate
leucine uses the leucine aminotransferase alpha-ketoglutarate
what are the three aromatic amino acids that derive from the combined PEP (phosphoenolpyruvate) and erythrose 4-phosphate?
- phenylalanine –> tyrosine is also synthesized from phenylalanine
- tyrosine
- tryptophan
