Anino Acid Metabolism Ii

Front 1

1. What pterin based cofactor is involved in adding or subtracting 1-carbon units?

2. Which co-enzyme, THF or THB is seen in rxns that transfer oxygen (hydroxylations), e.g., pehenylalanine hydroxylation associated with PKU.

3. which THB or THF contain pterin rings?

Back 1

1. THF

2. THB

3. both

Hint 1

None

Front 2

Give 3 sources for 1-carbon units.

Back 2

a) glycine cleavage system: breaks down glycine (2-carbons) into CO2, NH4 and a 1C unit… b) Histidine(6-C) to glutamine (5-C)… c) Serine/Threonine Hydroxymethyltransferase: converts serine (3-C) to glycine (2-C)

Hint 2

None

Front 3

What are the three parts of THF? Where do the 1-C units attach?

Back 3

glutamate residues (n=1-6), PABA, pterin ring. b) N-5 on pterin ring and N-10 on PABA

Front 4

Which THF with residues (n=1-6) can enter the cell membrane?

What part of the THF do the 1-C unit attach to?

Back 4

n=1

the N-5 or N-10

Hint 4

None

Front 5

What organism makes folate?

In what form can bacteria absorb THF?

Back 5

by bacteria

It can't, I must make all of it's own THF

Hint 5

None

Front 6

Where does Folate come from?

Back 6

GTP

Front 7

What is the name of the process where PABA is attached to the pterin ring?

Back 7

conjugation

Front 8

What enzyme do humans lack that render them unable to conjugate PABA to the pterin ring?

Back 8

dihydropteroate synthase

Hint 8

None

Front 9

Can humans make the pterin ring, such as those found on biopterin?

Back 9

yes

Front 10

Since bacteria makes PABA, it cannot absorb it. Thus it is essential that bacteria absorb the enzyme critical for the conjugation of PABA. What drugs inhibit bacterial growth and what related mechanism do these drugs use?

Back 10

Sulfa drugs… they mimic PABA and thus competitively inhibit PABA from binding dihydropteroate

Front 11

What are the 5 sources of 1-C units?

Back 11

serine, glycine, histadine, formaldehyde, Tryptophane (formate)

Hint 11

None

Front 12

1. What accept the 1-C units?

2. Besides THF and THB, which other coenzyme is based on the pterin ring?

Back 12

1. THF

2. folate

Hint 12

None

Front 13

What are the products of the 1-carbon units?

Back 13

dTMP, Serine, Purines, B12•CH3

Front 14

a) What are the 5 forms of folate, including folate that accept a 1-C unit. b) and which one isn't reversible?

Back 14

a) Folate, formyl-FH4, methenyl-FH4, Methylene-FH4 and Methyl-FH4… b) methyl-FH4

Front 15

Place the folate based carriers in order from least reduced to most reduced.

What is partly responsible for spina bifida?

Back 15

formyl-FH4 < methenyl-FH4 < Methylene-FH4 < Methyl-FH4

maternal folate deficiency

Hint 15

None

Front 16

Trace the pathway for the origin of 1-C unit entering into Formyl-FH4.

Back 16

Tryptophan -> formate + FH4 + ATP -> Formyl-FH4

Front 17

Trace the pathway for the origin of 1-C unit entering into Methenyl-FH4.

Back 17

Histidine -> forminino + FH4 -> glutamate + methenyl-FH4

Hint 17

None

Front 18

Trace the pathway for the origin of 1-C unit entering into Methylene-THF.

Back 18

(Glycine OR Serine OR Formaldehyde) + FH4

Front 19

What is the source of the Methyl-THF?

Back 19

reduction of methylene-FH4 by NADH

Front 20

Which folate based carriers are the most proximal to purine rings?

Back 20

formyl-FH4 and Methenyl-FH4

Front 21

1. which folate based carrier converts dUMP to dTMP?

2. Which Folate based carriers contribute 1-C units to DNA/RNA bases?

Back 21

1. Methylene-FH4

2. Formyl-FH4 and methylene-FH4

Hint 21

None

Front 22

What role does methyl-THF play in Homocystein degradation?

Back 22

it serves has a cofactor and contributes a methyl group in the methionine synthase rxn.

Front 23

What is required to convert homocystein to methionine?

Back 23

methyl-THF, B12

Front 24

What is another name for B12

Back 24

Cobalamin

Front 25

What is the path of the 1-carbon unit from the methyl-THF to S-Adenosylmethionine (SAM = Ado-Met)

Back 25

methyl-THF + Homocystein -(Methionine synthetase = homocysteine methyltransferase + B12 -> Methionine + free THF (to recycle) -> Methionine + ATP to form -> SAM

Hint 25

None

Front 26

What makes AdoMet (SAM) an effective methyl donor?

Back 26

The positive charge on the Sulfur to release -CH3

Front 27

1. Give the complete "Activated Methyl Cycle" starting with methyl-THF and ending with Homocystein.

2. which of the intermediates of the above cycle acts as the methyl handle?

Back 27

FH4-CH3 -> B12 -> homocystein -> methionine + ATP -> SAM (loss of CH3 to give) -> SAH (loss of adenosine to give) -> homocystein

2. which of the intermediates of the above cycle acts as the methyl handle? Homocysteine

Hint 27

None

Front 28

1. What is the most important metyl donor in the body?

2. a) What is the most common use of SAM as a methyl donor? b)Where does this occur?

Back 28

1. SAM (AdoMet)

2.
a) Guanidinoacetate + SAM -> creatine… b) in the liver

Hint 28

None

Front 29

1. What is the product of the following rxn: Norepinephrine + SAM -> ?

2. What did SAM do in the above rxn?

Back 29

1. epinephrine

2. donated a methyl group to NE

Hint 29

None

Front 30

Which enzyme catalyzes the methylization of homocystein?

Back 30

methionine synthase (=homocysteine transferase)

Front 31

Besides THF-CH3, how can homocysteine become methylated?

Back 31

degradation of choline (phosphatidylcholine) produces Betaine, which serves as a 1-carbon donor to homocysteine

Hint 31

None

Front 32

Where else can choline degradation contribute a 1-carbon unit?

Back 32

a product of choline degradation (dimethylglycine) can contribute

Front 33

On B12, what does the 1-carbon unit attach to? What does B12 resemble?

Back 33

cobalt… a heme... where the cobalt is analogous to Fe

Hint 33

None

Front 34

Skip

Back 34

skip

Hint 34

None

Front 35

How do we absorb B12?

Back 35

In the stomach R-binders and intrinsic factor are produced. R-binders bind B12 so it does not denature with HCl. Intestinal proteases release B12 from R-binders, while affinity of intrinsic factor for B12 increases. Specialized receptor in the Ileum binds intrinsic factor and B12 is shuttled across the membrane... then to the liver

Front 36

What is pernicious anemia?

Back 36

malabsroption of B12

Front 37

Where do R-binders come from?

Back 37

Gastric mucosa

Front 38

Where does intrinsic factor come from?

Back 38

parietal cells

Front 39

What happens as people age that impairs B12 absorption?

Back 39

lack of HCl (failure to breakdown meat products to capture B12)

poor intrinsic factor production, thus B12 does not bind to intestinal receptors and is excreted

Hint 39

None

Front 40

What does B12 deficiency lead to?

Back 40

megaloblastic anemia, because folate is not recycled… thus without purines and dTMP cells arrest in S-phase

Front 41

Besides methionine synthetase (homocysteine methyltransferase), which enzymes require B12

Back 41

methylmalonyl CoA Mutase

Front 42

1. What are the consequences of B12 deficiency with respect to methylmalonyl CoA Mutase?

2. what are the consequences of B12 deficiency with respect to homocysteine methyltransferase?

Back 42

1. neurologic which overtime may be irreversible (due to methylmalonyl CoA accumulation, demyelinization of nervous tissue, altered fatty acid synthesis

2. megaloblastic anemia and functional folate deficiency (which leads to loss of purine and thymidine base needed for DNA synthesis (stuck in S-phase)

Hint 42

None

Front 43

What is thought to be the cause of neurological symptoms in methylmalonyl CoA Mutase/B12 deficiency? (3 causes)

Back 43

1. Accumulation methylmalonyl CoA… 2. Demyelinization of nervous tissue… 3. Fatty acid biosynthesis affecting myelin synthesis: methylmalonyl CoA used instead of malonyl CoA… Priopionyl CoA used instead of acetyl CoA

Front 44

What supplies the sulfur for the production of cysteine?

Which cofactor is needed in the rxn that produces cysteine?

Back 44

homecysteine (or methionine)

PLP

Hint 44

None

Front 45

Give the pathway for cysteine synthesis from homocysteine.

Back 45

Homocysteine + (serine, PLP, cystathionine synthase also called CBS) --> cystathionine (cystathionase + PLP) --> cysteine

Front 46

Since homocysteine is linked with cardiovascular disease, which 5 deficiencies can lead to this condition?

Back 46

cytathionine synthase (CBS), vitamin B6 (PLP), homocysteine methyltransferase (methionine synthase), Methylene-THF reductase, choline