Lecture 5- Amino Acids and Nitrogen

Question 1

Are amino acids stored by the body? Y/N

Answer 1

No

Question 2

Where are amino acids obtained from?

Answer 2

Diet
Synthesized de novo
Produced from normal protein degradation

Question 3

What happens to excess amino acids?

Answer 3

They are rapidly degraded

Question 4

What is the first phase of amino acid catabolism?

Answer 4

Removal of the a-amino groups forming

• ammonia
• the corresponding a-keto acid

Question 5

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

Answer 5

A portion is excreted in the urine,

most is used in the synthesis of urea

Question 6

What is the second phase of amino acid catabolism?

Answer 6

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

Question 7

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

Answer 7

leaves as urea and ammonia

Question 8

In the stomach, which enzyme hydrolyzes proteins?

Answer 8

pepsin

Question 9

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

Answer 9

Pancreatic proteases- cleave polypeptides

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

Question 10

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

Answer 10

taken into the enterocytes

Question 11

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

Answer 11

keeps the amino acids protected from oxidative breakdown

Question 12

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

Answer 12

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

Question 13

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

Answer 13

Lysine

Threonine

Question 14

What is the result of deamination?

Answer 14

produces a free ammonia

Question 15

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

Answer 15

urea

Question 16

What produces urea?

Answer 16

liver

Question 17

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

Answer 17

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

Question 18

Disorder when too much ammonia is found in the blood

Answer 18

hyperammonemia

Question 19

glucogenic vs. ketogenic AA’s

Answer 19

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)

Question 20

Which AAs are only glucogenic?

Answer 20

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

Question 21

What AAs are glucogenic and ketogenic?

Answer 21

Tyrosine
Isoleucine
Phenylalanine
Tryptophan

Question 22

What AAs are only ketogenic?

Answer 22

Leucine

Lysine

Question 23

Arginine and proline can be synthesized from what?

Answer 23

Glutamate

Question 24

Two main disorders of AA metabolism

Answer 24

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

Question 25

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

Answer 25

Cyclic compounds that readily bind metal ions (usually iron) | Heme

Question 26

Major sites of heme biosynthesis?

Answer 26

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

Question 27

Which steps of the biosynthesis of heme happen where?

Answer 27

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

Question 28

When do red blood cells make heme?

Answer 28

before they are mature

Question 29

What is the sequence of heme degradation?

Answer 29

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

Question 30

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

Answer 30

via Heme oxygenase when Heme is converted to Biliverdin

Question 31

What is jaundice (icterus) caused by?

Answer 31

deposition of bilirubin

Question 32

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

Answer 32

Dopamine Norepinephrine Epinephrine All from Tyrosine

Question 33

Where are dopamine and norepinephrine synthesized?

Answer 33

brian (function as neurotransmitters)

Question 34

Where is epinephrine and norepinephrine synthesized?

Answer 34

adrenal medulla

Question 35

catecholamine(s) responsible for "fight or flight" response?

Answer 35

Norepinephrine and epinephrine

Question 36

Cause of Parkinson disease

Answer 36

insufficient dopamine production

Question 37

Catecholamines are inactivated by...?

Answer 37

deamination

Question 38

What are epinephrine, norepinephrine and dopamine broken down to?

Answer 38

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

Question 39

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

Answer 39

in the urine

Question 40

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

Answer 40

Histamine | Histidine

Question 41

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

Answer 41

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

Question 42

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

Answer 42

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

Question 43

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

Answer 43

muscle mass

Question 44

What is needed to make melanin?

Answer 44

tyrosine

Question 45

What are the two families of nucleotides?

Answer 45

purines | pyrimidines

Question 46

Which nucleotides are purines?

Answer 46

Adenine | Guanine

Question 47

Which nucleotides are pyrimidines?

Answer 47

Thymine Cytosine Uracil

Question 48

nucleoside vs nucleotide?

Answer 48

nucleotide is a nucleoside + phosphate group(s)

Question 49

Difference between a ribonucleoside and a deoxyribonucleoside?

Answer 49

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

Question 50

Where is the purine ring primarily constructed?

Answer 50

liver

Question 51

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

Answer 51

Ribose-5-phosphate pyrophosphokinase

Question 52

Glutamine and Glycine contribute in converting PRPP to...?

Answer 52

Inosine 5'-monophosphate (IMP)

Question 53

What two products are ultimately formed from IMP?

Answer 53

AMP and GMP

Question 54

What is the pathway from IMP to AMP?

Answer 54

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

Question 55

What is the pathway from IMP to GMP?

Answer 55

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

Question 56

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

Answer 56

Ribonucleotide reductase

Question 57

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

Answer 57

Gout

Question 58

What inhibits purine metabolism and how?

Answer 58

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

Question 59

What enzymes does 6-Mercaptopurine (purinethol) inhibit?

Answer 59

``` IMP dehydrogenase (IMPDH) and Adenylosuccinate synthetase ```

Question 60

What is an inhibitor of Ribonucleotide reductase?

Answer 60

Hydroxyurea

Question 61

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

Answer 61

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

Question 62

What is the beginning precursor to UMP?

Answer 62

Glutamine

Question 63

What is the path from UMP to dTMP?

Answer 63

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

Question 64

What catalyzes the conversion of dUMP to dTMP?

Answer 64

Thymidylate synthase

Question 65

What reduces dihydrofolate to tetrahydrofolate? and what inhibits it?

Answer 65

Dihydrofolate reductase | Can be inhibited by anti-cancer drugs

Question 66

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

Answer 66

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

Question 67

What are the products of pyrimidine degradation?

Answer 67

B-amino acids CO2 NH3

Question 68

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

Answer 68

the synthesis of IMP from hypoxanthine

Question 69

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

Answer 69

ribose 5-phosphate synthesis