L17: biosynthesis of nonessential & specialized AA's

Question 1

Creatine Kinase rxn

Answer 1

Creatine + ATP -> Creatine-P (“ATP buffer” in muscle)

Question 2

Keq for Creatine kinase rxn?

Answer 2

30

Question 3

Characteristics of Creatinine

Answer 3

• breaks down product of creatine-P in our muscle
• it is produced at a fairly constant uncatalyzed rate
• yield depends on muscle mass; higher in men
• clearance rate tells us how well the kidney is working

Question 4

3 reactions that form Glutamate

Answer 4

Transamination: alpha-KG + AA -> Glutamate + alpha-AA
Reductive amination: alpha-KG + NH3 + NADPH -> glutamate + NADP+
Hydrolysis: glutamine + H2O -> glutamate + NH3

Question 5

Enzymes for:

1. transamination
2. reductive amination
3. hydrolysis of glutamate

Answer 5

1. transaminase
2. GDH
3. glutaminase

Question 6

the reaction that forms Glutamine

Answer 6

glutamate + NH3 + ATP -> glutamine + ADP + Pi

Question 7

2 reactions that form Aspartate

Answer 7

Transamination: OAA + glutamate -> aspartate + alpha-KG
Hydrolysis: asparagine + H2O -> aspartate + NH3

Question 8

the reaction that forms Asparagine

Answer 8

Asp + Gln + ATP -> Asn + AMP + PPi + Glu

Question 9

the reaction that forms Alanine

Answer 9

Pyruvate + Glutamate -> alanine + alpha-KG

Question 10

What is the Alanine shuttle?

Answer 10

it is an inter-organ transfer of ammonia nitrogen. Alanine prevents ammonia toxicity.

Question 11

What is the key step in proline biosynthesis?

Answer 11

the reduction of glutamate to glutamate semi-aldehyde

Question 12

what can glutamate semi-aldehyde do?

Answer 12

it can undergo a side transamination reaction to form ornithine

Question 13

glutamate is a precursor for ___?

Answer 13

it is a precursor for arginine synthesis in the Urea Cycle

Question 14

hydroxyproline biosynthesis

Answer 14

prolyl residue + O=O + alpha-KG -> hydroxyprolyl residue + glutamate

Question 15

prolyl hydroxylase is ___?

Answer 15

it is easily deactivated, forming bound Fe(iii)-O-, which must be reduced by vitamin C to restore enzyme

Question 16

what does vitamin C deficiency lead to?

Answer 16

it leads to unstable collagen (the basis of Scurvy)

Question 17

what does hydroxyproline stabilize?

Answer 17

it stabilizes collagen by forming key hydrogen bonds within the tropocollagen triple helix

Question 18

Serine biosynthesis

Answer 18

can from 2 ways from 3-phosphoglycerate

Question 19

Tyrosine biosynthesis

Answer 19

Phe + NADPH + O2 -> Tyr + NADP+ + H2O

Question 20

deficiency in phenylalanine hydroxylase?

Answer 20

Phenylketonuria (PKU)- high serum Phe and high urinary phenylpyruvate

Question 21

Molecular basis of PKU?

Answer 21

rare genetic condition, autosomal recessive, blood Phe rises to 20X above the normal level

Question 22

Elevated Phe __?

Answer 22

damages nerve function

Question 23

is PKU a treatable disease?

Answer 23

Yes; requires strict “low-phenylalanine” diet, close supervision, becomes a balancing act when a PKU woman is pregnant.

Question 24

Cysteine biosynthesis

Answer 24

Methionine is a substrate needed.

Met + ATP -> S-adenosyl-methionine(SAM) -> S-adenosyl-homocysteine -> homocysteine -> cystathionine -> CYSTEINE

Question 25

Specialized AA synthesis: Thyroxin

Answer 25

look at slide 85 :)

Question 26

T3 is formed from T4 by ___?

Answer 26

peripheral deiodinase

Question 27

T3 binds to __?

Answer 27

mobile receptors/transcription factors

Question 28

T3 increases __?

Answer 28

basal metabolic rate: - increase O2 consumption and the rate of ATP hydrolysis - stimulates fat mobilization, raising plasma fatty acids - enhances insulin-dependent glucose uptake, gluconeogenesis, and glycogenolysis

Question 29

Which amino acids are neurotransmitters?

Answer 29

Glutamate, aspartate, D-Serine, and Glycine

Question 30

what is the main excitatory neurotransmitter?

Answer 30

glutamate (serine also excitatory)

Question 31

What are the neurotransmitters that are converted from amino acids?

Answer 31

- gamma-aminobutyric (glutamate) - dihydroxy-phenylalanine (phenylalanine) - serotonin (tryptophan)

Question 32

how is gamma-aminobutyric acid formed?

Answer 32

it is formed by the decarboxylation of L-glutamate in a vitamin B6-dependent reaction

Question 33

how is D-serine formed?

Answer 33

it is formed by the racemization of L-serine in a vitamin B6-dependent reaction

Question 34

Heme biosynthesis

Answer 34

- synthesized in a complex series of steps catalyzed by enzymes in mitochondrial and cytosolic compartments - the first step occurs in the mitochondrion

Question 35

Heme biosynthesis rxn

Answer 35

Succinyl-CoA + Glycine -> alpha-linolenic acid (ALA) + CoA + CO2

Question 36

What does ferrochelatase do?

Answer 36

it inserts Fe(ii) into protoporphyrin IX to form HEME

Question 37

Deranged heme production leads to ___?

Answer 37

anemia

Question 38

Iron deficiency is ___

Answer 38

a leading cause of anemia

Question 39

what replaces Fe2+ in iron deficiency?

Answer 39

Sn2+

Question 40

how does Pb2+ produce anemia?

Answer 40

by inhibiting heme synthesis; lead has a sweet taste making this s problem for children - ingested Pb2+ catalyzes DNA strand cleavage