Lecture 5- Amino Acids and Nitrogen Flashcards

1
Q

Are amino acids stored by the body? Y/N

A

No

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2
Q

Where are amino acids obtained from?

A

Diet
Synthesized de novo
Produced from normal protein degradation

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3
Q

What happens to excess amino acids?

A

They are rapidly degraded

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4
Q

What is the first phase of amino acid catabolism?

A

Removal of the a-amino groups forming

  • ammonia
  • the corresponding a-keto acid
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5
Q

What happens to the free ammonia that is removed in the first phase of amino acid catabolism?

A

A portion is excreted in the urine,

most is used in the synthesis of urea

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6
Q

What is the second phase of amino acid catabolism?

A

the carbon skeletons of the a-keto acids are converted to common intermediates of energy producing, metabolic pathways

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7
Q

Nitrogen enters the body in food, but how does the majority of it leave the body?

A

leaves as urea and ammonia

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8
Q

In the stomach, which enzyme hydrolyzes proteins?

A

pepsin

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9
Q

What enzymes act on proteins in the small intestine and what do they do?

A

Pancreatic proteases- cleave polypeptides

Aminopeptidases- produce even smaller peptides and free amino acids (cleave from amino end)

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10
Q

In the small intestines, what happens to the free amino acids?

A

taken into the enterocytes

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11
Q

What does the presence of the a-amino group on amino acids do?

A

keeps the amino acids protected from oxidative breakdown

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12
Q

What is the first step in the catabolism of most AA’s?

A

Transamination (transfer of their a-amino group to a-ketoglutarate), which is catalyzed by
aminotransferases

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13
Q

Which two amino acids do not participate in transamination in their catabolism, but instead use deamination?

A

Lysine

Threonine

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14
Q

What is the result of deamination?

A

produces a free ammonia

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15
Q

What is the major disposal form of amino groups derived from amino acids?

A

urea

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16
Q

What produces urea?

A

liver

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17
Q

What is the most important rate limiting step in the urea cycle, and what is its essential activator?

A

The conversion of CO2 and NH3 (ammonia) to carbamoyl phosphate by carbamoyl phosphate synthetase I.
N-Acetylglutamate is the essential activator

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18
Q

Disorder when too much ammonia is found in the blood

A

hyperammonemia

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19
Q

glucogenic vs. ketogenic AA’s

A

Glucogenic AAs- whose catabolism yields pyruvate or one of the intermediates of the TCA cycle
Ketogenic AAs- who catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA)

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20
Q

Which AAs are only glucogenic?

A
Alanine
Arginine
Asparagine
Aspartate
Glutamine
Glutamate
Glycine
Proline
Serine
Histidine
Methionine
Threonine
Valine
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21
Q

What AAs are glucogenic and ketogenic?

A

Tyrosine
Isoleucine
Phenylalanine
Tryptophan

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22
Q

What AAs are only ketogenic?

A

Leucine

Lysine

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23
Q

Arginine and proline can be synthesized from what?

A

Glutamate

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24
Q

Two main disorders of AA metabolism

A

Phenylketonuria (PKU)- results in over-accumulation of phenylalanine (deficiency of PHENYLALANINE HYDROXYLASE). Can cause mental retardation and other brain damage.
Albinism- lack of TYROSINASE, thus melanin not produced

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25
Q

What are porphyrins and what are the most prevalent in humans?

A

Cyclic compounds that readily bind metal ions (usually iron)

Heme

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26
Q

Major sites of heme biosynthesis?

A

Liver

Erythrocyte-producing cells of the bone marrow (~85%)

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27
Q

Which steps of the biosynthesis of heme happen where?

A

Initial reaction and the last 3 steps occur in the mitochondria.
Intermediate steps in the cytosol

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28
Q

When do red blood cells make heme?

A

before they are mature

29
Q

What is the sequence of heme degradation?

A

Heme to Biliverdin via Heme oxygenase
Biliverdin to Bilirubin via Biliverdin reductase
Bilirubin to Bile

30
Q

Where is the only known place in the body where CO is produced?

A

via Heme oxygenase when Heme is converted to Biliverdin

31
Q

What is jaundice (icterus) caused by?

A

deposition of bilirubin

32
Q

What are the three main catecholamines and what AA is responsible for them?

A

Dopamine
Norepinephrine
Epinephrine
All from Tyrosine

33
Q

Where are dopamine and norepinephrine synthesized?

A

brian (function as neurotransmitters)

34
Q

Where is epinephrine and norepinephrine synthesized?

A

adrenal medulla

35
Q

catecholamine(s) responsible for “fight or flight” response?

A

Norepinephrine and epinephrine

36
Q

Cause of Parkinson disease

A

insufficient dopamine production

37
Q

Catecholamines are inactivated by…?

A

deamination

38
Q

What are epinephrine, norepinephrine and dopamine broken down to?

A

epinephrine and norepinephrine –> Vanillylmandelic acid (VMA)
dopamine –> Homovanillic acid (HVA)

39
Q

Where are homovanillic acid (HVA) and vanillylmandelic acid (VMA) excreted?

A

in the urine

40
Q

What hormone is involved in allergic and inflammatory reactions and gastric secretion? What AA is needed for its synthesis?

A

Histamine

Histidine

41
Q

What does Seretonin function in, and what is needed to synthesize it?

A
Tryptophan to synthesize
functions:
-pain reception
-regulation of sleep
-appetite
-temperature
-blood pressure
-cognitive functions
-mood (well being)
42
Q

What is needed for the synthesis of creatine and what does it do?

A

Arginine and Glycine
High energy compound that provides a small but rapidly mobilized reserve of high energy phosphates (few minutes of intense muscular contraction)

43
Q

what is the amount of creatine phosphate in the body proportional to?

A

muscle mass

44
Q

What is needed to make melanin?

A

tyrosine

45
Q

What are the two families of nucleotides?

A

purines

pyrimidines

46
Q

Which nucleotides are purines?

A

Adenine

Guanine

47
Q

Which nucleotides are pyrimidines?

A

Thymine
Cytosine
Uracil

48
Q

nucleoside vs nucleotide?

A

nucleotide is a nucleoside + phosphate group(s)

49
Q

Difference between a ribonucleoside and a deoxyribonucleoside?

A

At Carbon 2, ribonucleoside has an OH and deoxyribonucleoside has a H

50
Q

Where is the purine ring primarily constructed?

A

liver

51
Q

what is the major enzyme involved in the synthesis of PRPP?

A

Ribose-5-phosphate pyrophosphokinase

52
Q

Glutamine and Glycine contribute in converting PRPP to…?

A

Inosine 5’-monophosphate (IMP)

53
Q

What two products are ultimately formed from IMP?

A

AMP and GMP

54
Q

What is the pathway from IMP to AMP?

A

IMP is converted to adenylosuccinate via
Adenylosuccinate synthetase, then to AMP via
Adenylosuccinate lyase

55
Q

What is the pathway from IMP to GMP?

A

IMP is converted to Xanthosine monophosphate (XMP) via
IMP dehydrogensase, then to GMP via
GMP synthase

56
Q

AMP and GMP are converted to the deoxy form by which enzyme?

A

Ribonucleotide reductase

57
Q

excessive amounts of uric acid not being excreted can cause…?

A

Gout

58
Q

What inhibits purine metabolism and how?

A

6-Mercaptopurine (purinethol) by inhibiting the enzymes that convert IMP to AMP and GMP

59
Q

What enzymes does 6-Mercaptopurine (purinethol) inhibit?

A
IMP dehydrogenase (IMPDH) and 
Adenylosuccinate synthetase
60
Q

What is an inhibitor of Ribonucleotide reductase?

A

Hydroxyurea

61
Q

What are a few important purine and pyrimadine analogues that are incorporated into the DNA, and analogues for which purine/pyrimidine?

A

Thioguanine- guanine analogue
Cytarabine- cytidine analogue
5-Azacytidine- cytidine analogue
Gemcitabine- fluorinated cytidine analogue

62
Q

What is the beginning precursor to UMP?

A

Glutamine

63
Q

What is the path from UMP to dTMP?

A

UMP –> UDP –> dUDP –> dUTP (briefly) –> dUMP –> dTMP

64
Q

What catalyzes the conversion of dUMP to dTMP?

A

Thymidylate synthase

65
Q

What reduces dihydrofolate to tetrahydrofolate? and what inhibits it?

A

Dihydrofolate reductase

Can be inhibited by anti-cancer drugs

66
Q

Name the three anti-cancer drugs discussed and what enzyme they inhibit

A

5-Fluorouracil- thymidylate synthase
Capecitabine- thymidylate synthase
Methotrexate- dihydrofolate reductase

67
Q

What are the products of pyrimidine degradation?

A

B-amino acids
CO2
NH3

68
Q

The type of enzyme known as a phosphoribosyltransferase is involved in what?

A

the synthesis of IMP from hypoxanthine

69
Q

if a cell were unable to synthesize PRPP, what process would likely be directly impaired?

A

ribose 5-phosphate synthesis