Lecture 36: Amino Acids as Precursors

Question 1

What are the 4 functions of glycine as a precursor?

Answer 1

1. Inhibitory transmitter
2. Glycocholic acid (bile salt)
3. Purine synthesis
4. Heme synthesis

Question 2

Describe glycine’s function as an inhibitory transmitter.

Answer 2

It inhibits impulses traveling down the spinal cord to stimulate skeletal muscle

Question 3

How does glycine contribute to purine synthesis?

Answer 3

It’s directly incorporated into de novo purine synthesis

Question 4

What are the 2 purines?

Answer 4

1. Adenine

2. Guanine

Question 5

How does glycine contribute to heme synthesis?

Answer 5

Glycine condenses with succinyl-CoA in the first step of heme synthesis and is a building block for porphyrin 9 which coordinates with iron

Question 6

What are the 2 predominant circulating AAs?

Answer 6

1. Alanine

2. Glutamine

Question 7

What is the main function of serine?

Answer 7

Important source of single carbon fragments (from the R group) => transferred to a folate derivative which can use the C in a variety of ways depending on its oxidative/reductive state (tetrahydrofolates)

Question 8

What are the 3 functions of glutamine?

Answer 8

1. Amino group and NH4+ transporter
2. Amino group donor for purine biosynthesis
3. Amino group donor for amino sugar biosynthesis

Question 9

Describe the synthesis of amino sugars.

Answer 9

Glutamine donates an amino group to F6P which produces glucosamine-6-phosphate => all amino sugars are derived from glucosamine-6-P

Question 10

What are the 4 functions of glutamate?

Answer 10

1. Excitatory NT
2. Precursor to GABA
3. Amino group donor for AA synthesis
4. Ammonia fixation reactant

Question 11

Describe the synthesis of GABA.

Answer 11

Decarboxylation of alpha carboxyl using PLP as a cofactor = GABA

Question 12

What does GABA stand for?

Answer 12

γ-amino butyrate

Question 13

What drugs is the GABA receptor a target for?

Answer 13

Benzodiazepines and barbiturates

Question 14

What are the 2 functions of methionine?

Answer 14

1. Methyl group source

2. Polyamine synthesis

Question 15

How does methionine donate a methyl group?

Answer 15

Methionine + ATP => S-adenosyl methionine (SAM)

Question 16

What is another name for S-adenosyl methionine (SAM)?

Answer 16

Ado-met

Question 17

How does methionine contribute to polyamine synthesis?

Answer 17

SAM is decarboxylated using PLP leaving behind propylamine residue attached to sulfur which serves as a precursor for polyamines

Question 18

What are 2 examples of polyamines? What is their role?

Answer 18

1. Spermine
2. Spermidine
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Question 19

What are the 2 functions of arginine?

Answer 19

1. Urea precursor

2. NO source

Question 20

What is the function of NO?

Answer 20

Short-lived second messenger that acts near its synthesis site

Question 21

What 2 cofactors does NO synthesis from arginine require?

Answer 21

1. Flavin

2. Tetrahydrobiopterin

Question 22

What 3 AAs contribute to the synthesis of creatine?

Answer 22

1. Glycine
2. Arginine
3. Methionine

Question 23

What is the main function of histidine? Describe the mechanism

Answer 23

Histamine precursor via histidine decarboxylation

Question 24

What are the 2 main functions of histamines

Answer 24

1. Stimulates systemic reactions to allergens

2. Stimulates acid release in the stomach

Question 25

What cofactor does the synthesis of histamines from histidine require?

Answer 25

PLP

Question 26

What is the main function of phenylalanine?

Answer 26

Precursor for tyrosine

Question 27

What are the 10 essential AAs (meaning we cannot make them)?

Answer 27

I Want To Kill VHRs. FML

Question 28

Describe the mechanism of tyrosine synthesis using phenylalanine (overall and 2 steps)

Answer 28

Coupling of 2 enzymes through the cofactor tetrahydrobiopterin: 1. Dihydrobiopterin reductase: NADH + 7,8-dihydrobiopterin => NAD+ + 5,6,7,8-tetrahydrobiopterin 2. Phenylalanine hydroxylase: 5,6,7,8-tetrahydrobiopterin + phenylalanine + O2 => tyrosine + H2O + 7,8-dihydrobiopterin

Question 29

What is phenylketonuria (PKU)? When is this screened for? Treatment?

Answer 29

Phenylalanine hydroxylase deficiency: excess phenylalanine impairs neural development Screened for at birth Treatment: inhibit intake of phenylalanine and take tyrosine supplements

Question 30

What is a deficiency in the enzyme dihydrobioterin reductase? Consequences?

Answer 30

Inability to regenerate the cofactor biopterin, which is used in many reactions: very serious consequences

Question 31

What are the 3 functions of tyrosine?

Answer 31

1. Catecholamine synthesis 2. Thyroid hormone precursor 3. Melanin precursor

Question 32

Describe the catecholamine synthesis pathway.

Answer 32

Tyrosine → Dopa (decarboxylation) → Dopamine → Norepi → Epi

Question 33

What cofactor is needed for the conversion of tyrosine to dopa?

Answer 33

Biopterin

Question 34

How is melanin synthesized?

Answer 34

Tyrosinase: dopa oxidation

Question 35

What is albinism caused by?

Answer 35

Tyrosinase deficiency

Question 36

What are the 3 functions of tryptophan?

Answer 36

1. Serotonin precursor 2. Nicotinic acid precursor 3. Indoleacetate precusor

Question 37

How is serotonin synthesized? Cofactors used?

Answer 37

Hydroxylation of tryptophan at C5 using biopterin + decarboxylation using PLP

Question 38

List the 7 reactions that require PLP as a cofactor? What reactions are these?

Answer 38

1. Glutamate → GABA 2. α-ketoglutarate + amino acid → glutamate + -keto acid (transamination) 3. SAM → precursor of polyamines 4. Ornithine → putrescine 5. Histidine → histamine 6. Dopa → dopamine 7. Tryptophan → serotonin All decarboxylations except for #2: transamination

Question 39

List the 3 reactions that require Tetrahydrobiopterin as a cofactor? What reactions are these?

Answer 39

1. Arginine → NO 2. Phenylalanine → tyrosine 3. Tryptophan → serotonin All hydroxylations

Question 40

Describe the synthesis of nicotinic acid. What is it used for? Enough to eliminate dietary need?

Answer 40

Tryptophan degradation => nicotinic acid: NAD+ precursor NOPE, not enough

Question 41

Write out the reaction of ammonia fixation using glutamate.

Answer 41

Glutamate + NH4+ + ATP => glutamine + ADP + Pi + H+

Question 42

What cells produce NO?

Answer 42

1. Macrophages 2. Vascular endothelial cells 3. Neurons 4. Hepatocytes

Question 43

Function of Indoleacetate?

Answer 43

Plant growth factor to do geotropism and phototropism