Exam 3 December 2 Lecture

Question 1

What are the difference between glucogenic and ketogenic amino acids?

Answer 1

glucogenic amino acids are used to make glucose while ketogenic amino acids can make acetyl CoA → some amino acids can be both glucogenic and ketogenic

Question 2

What are amino acids used for?

Answer 2

1. usually reserved for protein synthesis
2. excess amino acids in the diet are utilized as an energy source
3. during prolonged fasting, amino acids in skeletal muscles are released → start to digest our own amino acids

Question 3

What is the importance of amino acids?

Answer 3

1. our body can’t make many amino acids so we need to get them from the diet → is essential unlike glucose which our liver can make
2. amino acids have nitrogen (most abundant atom in our bodies is carbon, hydrogen, oxygen, then nitrogen) → amino acids are our nitrogen source (especially if we want to make nucleic acids)

Question 4

How many ketogenic amino acids are there?

Answer 4

only 2 → leucine and lysine

Question 5

What are the fates of the glucogenic amino acids?

Answer 5

some become various intermediates of the TCA cycle and enter in at different points

Question 6

What are the fates of the ketogenic amino acids?

Answer 6

become acetoacetate that can become acetyl CoA that can then enter the TCA cycle

Question 7

What is the fate of asparagine and aspartate as glucogenic amino acids?

Answer 7

they can become oxaloacetate that can then enter the TCA cycle or be converted to phosphoenolpyruvate (PEP) that can be made into glucose or enter back into the TCA cycle by being converted to pyruvate then acetyl CoA

Question 8

How is an α-keto acid created?

Answer 8

the removal of the amine group from amino acids → some of the α-keto acids are readily available as intermediates in glycolysis or the TCA cycle

Question 9

What are some α-keto acids and their amino acid counterparts?

Answer 9

1. alanine ↔ pyruvate (final product of glycolysis)
2. aspartate ↔ oxaloacetate (intermediate in the TCA cycle)
3. glutamate ↔ α-ketoglutarate (intermediate in the TCA cycle)

Question 10

How is an amino acid deemed as essential?

Answer 10

when the corresponding α-keto acids are not produced in the human body, the amino acid is called nutritionally essential

Question 11

Which amino acids are essential?

Answer 11

the branched amino acids → valine, leucine, and isoleucine

Question 12

What are the essential amino acids and their α-keto acid counterpart?

Answer 12

1. valine ↔ α-ketoisovalerate
2. leucine ↔ α-ketoisocaproate
3. isoleucine ↔ α-keto-β-methylvalerate

Question 13

What is transamination?

Answer 13

the removal of the amine group from an amino acid is coupled with the production of glutamate from α-ketoglutarate → catalyzed by amino acid specific aminotransferases (or transaminases)

Question 14

What is an example of a transamination reaction?

Answer 14

alanine to pyruvate with α-ketoglutarate to glutamate (so alanine + α-ketoglutarate ↔ pyruvate + glutamate)

Question 15

What are the two exceptions that do not have a transamination reaction?

Answer 15

threonine and lysine

Question 16

What is pyridoxal phosphate (PLP)?

Answer 16

1. a co-factor for many amino acid metabolizing enzymes like aminotransferases
2. active form of vitamin B6
3. forms a Schiff base (aldimine) with amine groups → lysine side chain of enzymes and amine groups of amino acids

Question 17

What does the structure of pyridoxal phosphate look like?

Answer 17

has an aldehyde group and a phosphate group in which the aldehyde can form a Schiff base with a lysine residue → forms an aldimine (aldehyde + amine)

Question 18

What is important to note about the transamination reaction?

Answer 18

it is reversible! α-ketoglutarate can come in to do the reverse reaction to produce glutarate
(amino acid + pyridoxal phosphate (PLP) ↔ aldimine ↔ ketimine ↔ α-keto acid (from the amino acid) + pyridoxamine phosphate (PMP, from PLP))

Question 19

What happens during the transamination reaction between the aldimine and the ketimine?

Answer 19

tautomerization in which the double bond is broken when hydrolyzed in the ketimine form

Question 20

What is oxidative deamination and what does glutamate dehydrogenase have a role in it?

Answer 20

1. amine groups of amino acids are released as ammonia
2. glutamate dehydrogenase removes the amine group from glutamate by producing ammonia and NADH
3. glutamate dehydrogenase catalyzes the reverse reaction using NADPH but under normal conditions, [NH4+] is too low for the reaction to occur
   (glutamate ↔ α-ketoglutarate + NH4+)

Question 21

What is oxidative deamination and what does amino acid oxidase have a role in it?

Answer 21

1. amino acid oxidase removes the amine group of an amino acid as ammonia → like glutamate dehydrogenase
2. not significant contribution to metabolism
   (amino acid → intermediate → α-keto acid + NH4+)

Question 22

What happens because ammonia is toxic?

Answer 22

ammonia is transported into a nontoxic form as amino acids (glutamine and alanine)

Question 23

What is the most abundant circulating amino acid?

Answer 23

glutamine

Question 24

What does glutamine synthetase do?

Answer 24

produces glutamine from glutamate and ammonia → reaction requires ATP

Question 25

What happens when glutamine is produced?

Answer 25

most glutamine is transported to the intestine and then converted to alanine and ammonia

Question 26

In the liver, alanine is converted to what?

Answer 26

1. pyruvate → glucose (gluconeogenesis) | 2. ammonia → urea (urea cycle)

Question 27

Why is glutamine a good way to transport nitrogen?

Answer 27

it has 2 nitrogen molecules in its structure

Question 28

What is the flow of nitrogen?

Answer 28

1. amino acids → glutamate (by transamination) → alanine → NH4+ → urea (by the urea cycle) 2. amino acids → glutamate (by transamination) → NH4+ (by oxidative deamination) → glutamine → NH4+ → urea (by urea cycle) 3. amino acids → glutamate (by transamination) → NH4+ (by oxidative deamination) → glutamine → alanine → NH4+ → urea (by urea cycle) 4. amino acids → NH4+ (by oxidative deamination) → glutamine → alanine or NH4+ to then urea

Question 29

What are the different metabolites derived from amino acids?

Answer 29

1. glutamate → γ-aminobutyrate (GABA) 2. tyrosine → dopamine, norepinephrine, epinephrine 3. tryptophan → serotonin, melatonin 4. histidine → histamine 5. glycine → oxalate

Question 30

What is γ-aminobutyrate (GABA)?

Answer 30

an inhibitory neurotransmitter produced GABAergic neurons and is produced from glutamate by glutamate decarboxylase (CO2 is lost) → reduces neuronal excitability so neurons become quieter → causes a negative change in the membrane potential (hyperpolarization)

Question 31

What is unique about glutamate?

Answer 31

glutamate as is (itself) can function as an excitatory neurotransmitter

Question 32

What is the effect of alcohol on GABA?

Answer 32

it induces GABA neurons which makes you sleepy since it is an inhibitory neurotransmitter

Question 33

Catecholamine synthesis is using which amino acid?

Answer 33

tyrosine

Question 34

What is dopamine?

Answer 34

a neurotransmitter in which the end product in the substantia nigra of the brain controls mood, pleasure, and movement → insufficient production of dopamine causes Parkinson disease

Question 35

In the adrenal medulla, what is dopamine further converted to?

Answer 35

dopamine → norepinephrine → epinephrine (in which both are fight or flight hormones)

Question 36

How are catecholamines synthesized?

Answer 36

tyrosine → L-DOPA (catechol produced) → dopamine (amine group is removed) → norepinephrine (hydroxyl group added) → epinephrine (methyl group added)

Question 37

What are some examples of catecholamines?

Answer 37

dopamine, norepinephrine, epinephrine

Question 38

What does the root word "nor" mean?

Answer 38

that it's missing a methyl group (the difference between norepinephrine and epinephrine is that epinephrine has a methyl group added to it)

Question 39

What is a major tryptophan derivative?

Answer 39

serotonin

Question 40

What is serotonin?

Answer 40

a neurotransmitter in the CNS that regulates mood, appetite, and sleep in addition to regulating the gastrointestinal motility in the GI tract

Question 41

What is another common tryptophan derivative?

Answer 41

melatonin

Question 42

What is melatonin?

Answer 42

involved in regulation of the circadian rhythm and is synthesized mostly at night and induces sleep

Question 43

Many antidepressants are what?

Answer 43

SSRIs since serotonin is important in regulating mood

Question 44

How are serotonin and melatonin derived from tryptophan?

Answer 44

tryptophan → 5-hydroxytryptophan (hydroxyl group is added) → serotonin (carboxylic acid group is removed) → melatonin (hydroxyl group is changed to an ether group and amine group is changed to an amide group)

Question 45

How is histamine produced?

Answer 45

produced by the decarboxylation of histidine

Question 46

What is histamine?

Answer 46

released from cells as an allergic response which causes vasodilation and itchiness (from the histamine H1 receptor) → acts as a neurotransmitter in the CNs that promotes wakefulness (histamine H1 receptor in the brain) → can also promote gastric acid release (histamine H2 receptor in the stomach)

Question 47

What is an example of a drug that inhibits histamine's promotion of gastric acid release (aka targets the histamine H2 receptor)?

Answer 47

xantac which is an acid reducer

Question 48

What is a prominent side effect of histamine H1 receptor targets?

Answer 48

sleepiness (example is Benadryl) → blocks signaling of histamine in the brain and induces sleep

Question 49

The oxidation of glycine produces what?

Answer 49

oxalate

Question 50

What's the importance of oxalate?

Answer 50

1. excessive production of oxalate (hyperoxaluria) forms the insoluble calcium oxalate salt which can lead to kidney stones (if it builds up in the bloodstream) 2. about 50% of oxalate comes from the diet → peanuts, spinach, chocolate (want to be careful of these foods)

Question 51

What causes primary hyperoxaluria?

Answer 51

the lack of the enzyme activity converting glyoxylate to glycine

Question 52

What is the process (reaction) from glycine to oxalate?

Answer 52

glycine → glyoxylate (amine group gets removed to make an aldehyde) → oxalate (aldehyde group gets oxidized to become oxalate using NAD+)