Purine Metabolism - Lec. 33

Question 1

what two amino acids are the critical regulators of nitrogen (or amino acids) synthesis in our cells?

Answer 1

glutamate and glutamine

- they serve as a sensor of nitrogen levels in cells

Question 2

glutamine synthetase

Answer 2

converting glutamate into glutamine by consuming a molecule of ATP and ammonia
- it is allosterically regulated

Question 3

how is glutamine made?

Answer 3

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

Question 4

what is glutamine capable of regulating? (what biomolecules)

Answer 4

• AMP
• CTP
• tryptophan
• histidine
• carbamoyl phosphate

Question 5

what does carbamoyl phosphate do?

Answer 5

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

Question 6

how is glutamine synthetase allosterically regulated?

Answer 6

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

Question 7

allosteric regulation

Answer 7

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)

Question 8

how is glutamine formed? (what enzyme)

Answer 8

glutamine is formed through a molecule of glutamate that is converted by the enzyme glutamine synthetase –> glutamine synthetase is allosterically regulated

Question 9

how is glutamate formed in bacteria and plants? (by what enzyme)

Answer 9

glutamate is formed through the enzyme glutamate synthase (different than glutamate synthetase - which converts glutamate to glutamine)

Question 10

glutamate synthase enzyme

Answer 10

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

Question 11

how do humans form glutamate? (two different mechanisms)

Answer 11

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

Question 12

essential amino acids

Answer 12

means that the amino acid cannot be synthetized by most mamamilian cells and it needs to be obtained through dietary proteins/foods we eat

Question 13

essential amino acids (9) - name them

Answer 13

• phenylalanine
• valine
• tryptophan
• threonine
• isoleucine
• methionine
• histidine
• leucine
• lysine

Question 14

nonessential amino acids (5) - name them

Answer 14

• alanine
• asparagine
• aspartate
• glutamate
• serine

Question 15

nonessential amino acids

Answer 15

nonessential amino acids means that those ones can be easily synthesized in our cells from other metabolite (nonessential and conditionally essential)

Question 16

conditionally essential amino acids (6) - name them

Answer 16

• arginine
• cysteine
• glutamine
• glycine
• proline
• tyrosine

Question 17

3 critical amino acids for the TCA cycle? HINT: GAA

Answer 17

• glutamate –> can be converted to alpha-ketoglutarate
• aspartate –> can be converted to oxaloacetate
• alanine –> can be converted to pyruvate

Question 18

what are the critical regulators of amino acid synthesis or nitrogen metabolism (urea cycle)?

Answer 18

• glutamate

- glutamine

Question 19

where does the amino group for amino acid synthesis come from? (what two amino acids)

Answer 19

• glutamine

- glutamate

Question 20

amino acid synthesis

Answer 20

• 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

Question 21

what amino acids can form from a molecule of glutarate?

Answer 21

• glutamine
• proline
• arginine through

Question 22

through transamination what will form from a molecule of alpha-ketoglutarate (if it combines with an amino group)

Answer 22

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

Question 23

what is arginine synthesized from? (think back to beginning of urea cycle)

Answer 23

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)

Question 24

how to do humans synthesize proline from ornithine?

Answer 24

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

Question 25

how does serine derive from 3PG (3-phosphoglycerate)?

Answer 25

serine derives from 3PG through two different enzymatic process by undergoing oxidation and then transamination and lastly dephosphorization to produce serine

Question 26

in reference to serine, what other amino acids usually group together with it?

Answer 26

serine is typically coupled with glycine and cysteine

Question 27

how is cysteine synthesized from homocysteine and serine?

Answer 27

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

Question 28

where does the sulfur come from during the synthesis of cysteine from serine and homocysteine?

Answer 28

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

Question 29

what does oxaloacetate produce through transamination (addition of an amino group)

Answer 29

through transamination oxaloacetate (OAA) will convert to aspartate by adding an amino group

Question 30

once oxaloacetate produces a molecule of aspartate through transamination (adding an amino group) what can aspartate produce? (what 4 amino acids can be synthesized)

Answer 30

• asparagine through transamination (add amino group)
• methionine
• lysine
• threonine –> threonine can also be further converted into isoleucine

Question 31

what are the amino acids which are synthesized through pyruvate? (mnemonic: pyruvate (I)s (A)ll (V)ery (L)eucy

Answer 31

• alanine
• valine
• leucine
• isoleucine

Question 32

what are the branched amino acids that can undergo branched amino acid degradation? (LIV –>they call come from pyruvate)

Answer 32

valine
leucine
isoleucine
*** these all come from pyruvate
* know this

Question 33

does isoleucine have an amino transferase enzyme?

Answer 33

no. isoleucine instead uses the valine aminotransferase alpha-ketoglutarate enzyme to convert the ketone to an amino group

Question 34

what is the name of the aminotransferase used for valine and leucine?

Answer 34

valine uses the valine aminotransferase alpha-ketoglutarate

leucine uses the leucine aminotransferase alpha-ketoglutarate

Question 35

what are the three aromatic amino acids that derive from the combined PEP (phosphoenolpyruvate) and erythrose 4-phosphate?

Answer 35

• phenylalanine –> tyrosine is also synthesized from phenylalanine
• tyrosine
• tryptophan