Amino Acid Metabolism I

Front 1

Is tyrosine an essential amino acid?

Back 1

No, but it is derived from phenylalanine, which is an essential amino acid

Front 2

Which amino acid are derived from oxaloacetate in a transamination, PLP rxn?

Which amino acid can be derived from that transamination?

Back 2

(a) Asparate

(b) Asparagine

Front 3

How is Asp related to Asn?

Which 2 enzymes makes this possible?

Back 3

Asparagine is derived by the addition of an amine group: which requires: Aspartate, Glutamate, ATP and Asparagine synthetase

The reverse rxn produces Aspartate from Asparagine, required: Asparagine, asparaginase and H2O

Hint 3

None

Front 4

(a) Which amino acids are related to ∂-KG?

(b) Which is the central amino acid that links all these amino acids?

Back 4

a) Glu, Gln, proline, arginine, histidine…

b) glutamate

Front 5

How is proline linked to glutamate?

Back 5

glutamate <-> gluamate semialdehyde <-> pyrroline 5-carboxylate <-> proline

Front 6

a) What form of energy and what reducing agent are required in the formation of proline from glutamate.

b) at which stage of the glutamate to proline pathway is energy needed?

c) at which which points in the rxn is a reduciing agent needed?

d) what is need to produce Glutamate from Proline?

Back 6

a) ATP and NADPH…

b) glutamate <-> glutamate semialdehyde.

c) Glutamate --> Glutamate semialdehyde and Pyrroline 5-carboxylate --> proline (both require NADPH)

d) an oxidizing agent to reverse the rxn: proline --> pyrroline 5-carboxylate requires FAD+) and glutamate semialdehyde --> glutamate (requires NAD+)

Front 7

Besides proline, which amino acid is glutamate semialdehyde a precursor to?

Back 7

arginine

Hint 7

None

Front 8

How is arginine linked to glutamate?

How is this different from the urea cycle?

Back 8

1. glutamate <-> gluamate semialdehyde <-> ornithine <-> arginine

2. The formation of arginine from ornithine occurs in the liver as a means of eliminating excess Nitrogen. To produce arginine from glutamate requires the cooperative actions of the intestinal and kidney cells.

Front 9

How do the intestine and the kidney work together to form arginine from ornithine?

Name the requried enzymes

Back 9

a) the intestines have the enzyme that convert glutamate --> ornithine --> citruline…

b) the citrulline is passed through the blood stream to the kidneys

c) the kidneys have the enzyme (arginase) that convert citrulline to arginine

Hint 9

None

Front 10

Why is it that the arginine made in the liver, as part of the urea cycle, is not useful?

Back 10

because of the large amount of arginase in the liver, the produced arginine would be broken down into ornithine as a means to eliminate unwanted nitrogen… thus arginine in the circulation is produced by the intestines and the kidneys where the product (arginine) is not converted to ornithine.

Front 11

How is Histidine synthesized from glutamate?

Back 11

Tt's not, it an essential amino acid. However, Glutamate is synthesized from Histidine.

Hint 11

None

Front 12

Glutamate and histidine are related to each other (Histidine ->->-> glutamate) but glutamate has 5 carbons, where histidine has 6 carbons. What happens to the other carbon?

Back 12

the extra carbon is transferred to THF (which binds 1-carbon units)

Hint 12

None

Front 13

What are the four amino acids related to ∂-KG (glutamate)?

Back 13

arginine, histine, Gln, proline

Front 14

Can humans synthesize phenyl rings?

Back 14

no

Front 15

Which amino acids have phenyl rings?

Back 15

phenylalanine, tryptophan, and tyrosine

Front 16

Why is tyrosine not an essential amino acid?

Back 16

tyrosine is synthesized from phenylalanine

Front 17

Phenyl ring amino acids can be degraded to fumarate and acetoacetate. Given this fact, are phenyl ring amino acids (tyrosine, phenylalanine, and tryptophane) glucogenic or ketogenic?

Back 17

Both: phenyl ring amino acids are ketogenic via acetoacetate and glucogenic via fumarate

Hint 17

None

Front 18

(a) Which enzyme and cofactor are required for the conversion of phenylalanine to tyrosine?

(b) What can inhibit the production of tyrosine?

Back 18

(a) phenylalanine hydrolase (adds an -OH group) and tetrahydrobiopterin (BH4)

(b) the lack of the above

Front 19

What two cofactors contain a pterin ring?

Back 19

BH4 (or THB) and THF

Front 20

Can humans synthesize BH4 (tetrahydrobiopterin)?

Back 20

yes, from GTP

Front 21

Can humans synthesize THF?

Back 21

no

Front 22

What is BH4, which is needed in the conversion of Phe to Tyr, made from?

Back 22

GTP

Front 23

(a) What does BH4 converted back and forth from and to?

(b) What is needed in this conversion?

Back 23

(a) BH4 <-> BH2

(b) A reducing agent, NADH, and an oxidizing agent O2 --> H2O

Front 24

What amino acid degradation occurs in tandem with the BH4 to BH2 rxn?

Back 24

Phe to Tyr

Front 25

a) What is needed to convert BH2 back to BH4?

b) Is energy required and in what form?

Back 25

a) dihydrobiopterin reductase…

b) a reducing agent ,NADH

Front 26

What are the 3 causes of PKU (Hint: phenylketonuria is an excess of Phe in the urine)

Back 26

a) defective enzymes in the GTP >>> BH4 synthesis…

b) defect in phenylalanine hydrolase (which is the enzyme that drives the Phe to Tyr rxn)…

c) defect in the dihyropteridine reductase... (or lack of NADH)

Front 27

what was the first inborn error of the metabolism linked directly to an enzyme deficiency?

Back 27

PKU related to a deficiency of phenylalanine hydrolase (PAH)

Hint 27

None

Front 28

the phenoketone, phenylpyruvate, is elevated in PKU due to transamination from phenylalanine and is the classical method of diagnosis. What is really causing the problem in PKU?

Back 28

elevated levels of phenylalanine

Front 29

How is PKU diagnosed?

Back 29

fluormetry or bacterial inhibition assay

Front 30

What type of inheritance is PKU attributed to?

Back 30

autosomal recessive

Front 31

What is the dietary restriction for people with PKU?

Back 31

500-600 mg Phe/day

Front 32

What are the IQ effects of treating and untreating PKU on individuals?

Back 32

untreated 1% IQ>70… treated normal IQ >90%

Front 33

What impact does aspartame have on people with PKU

Back 33

aspartame is catalized to produce aspartate, phenylalanine and methanol, thus people with PKU are increasing their intake of phenylalanine

Hint 33

None

Front 34

What is the concern for PKU-moms?

Back 34

If they don't watch their diets, the fetus can suffer elevated blood levels of phenylalanine (not urinary phenylketones) which has teratogenic effects… even if the child is heterozygous… ALSO, too little Phe will have an effect on biosynthesis

Hint 34

None

Front 35

What is Tryptophan synthesized from in the body?

What is produced in the degradation of Trp?

Back 35

It's not, it's an essential AA

Formate (a 1-carbon unit, taken up by THF), alanine, acetyl CoA, and Nicotinamide (NAD and NADP... although most is obtained in the diet)

Hint 35

None

Front 36

a) What are the 3 amino acids branched chain amino acids (BCAA)? b) Are these amino acids essential or nonessential?

Back 36

a) Val, Ile, Leu… b) all three are essential

Hint 36

None

Front 37

Of the BCAA, which are glucogenic and which are ketogenic?

Back 37

Leu is ketogenic (producing acetoacetate) , Val and Ile are glucogenic (producting propionyl CoA, which leads to succinyl CoA in the TCA cycle)

Front 38

What are the 3 reactions associated with BCAA degradation?

Which branched amino acid, (leucine, valine, or isoleucine), produce a ketone?

Back 38

1. transamination, oxidative decarboxylation, dehydrogenation

2. leucine --> acetoacetyl CoA

Hint 38

None

Front 39

a) What is the first step in BCAA degradation and why doesn't occur in the liver? b) Why is this important?

Back 39

a) Deamination, the liver lacks the needed transaminases… b) BCAAs are the major source of energy for some tissue.

Front 40

what % of the essential amino acids do BCAA account for?

Back 40

35-40%

Front 41

What are the 3 common steps in BCAA degradation?

Back 41

Transaminase converts BCAA to an ∂-keto acid… b) oxidative decarboxylation converts ∂-keto acid to a CoA-thioester by BCKA dehydrogenase… c) CoA-thioester is the dehydrogenated

Hint 41

None

Front 42

BCKA dehydrogenase is seen in the third step of Branched Chain Amino Acid metabolism, which 2 other enzymes is the BCKA dehydrogenase enzyme similar to ?

Back 42

pyruvate dehydrogenase and ∂-KG dehydrogenase (which converts ∂-KG to succinyl CoA

Hint 42

None

Front 43

What are the steps of the BCKA dehydrogenase enzyme complex?

Back 43

1) decarboxylation (attatchment of the ∂-KA to Thiamine PPi)…

2) transfer of the fragment to lipoamide to form a thioester…

3) Transfer of the acyl group to CoA and release of this molecule from the enzyme…

4) regeneration of the oxidized lipoamide by the reduction of FAD by dihydrolipoyl DH...

5) oxidation of FADH2 by the reduction of NAD+

Hint 43

None

Front 44

What is the first step in the BCKA dehydrogenase reaction catalyzed by? And what is it composed of?

Back 44

E1 = subunit ∂ an ß

Front 45

What is the term for the mutation in BCKA dehydrogenase and what does it mean?

Back 45

Y393N: it means that a mutation on the E1∂ subunit has replaced asparagine with a tyrosine.

Front 46

What is the lay term for Y393N mutation and what are the clinical manifestations?

What is the Rx for this disease?

Back 46

Maple syrup disease, it is fatal if low BCAA diet is not observed… Seen in "Old Mennonite" and Amish population of SE Penn.

Low dietary intake of BCAA

Hint 46

None

Front 47

Which amino acids are associated with glycolytic intermediates?

Back 47

Alanine, Serine, Glycine

Front 48

Are the amino acids associated with the glycolytic pathway essesntial?

Back 48

No

Front 49

1. Summarize how serine can be synthesized in the glycolytic pathway and how it can enter the glycolytic pathway.

2. What regulates the synthesis of serine?

Back 49

Glycine <-> Serine from a 3-phosphoglycerate intemediate->

Serine -> can re-enter the glycolytic pathway via by first being metabolized to 2-phosphoglycerate

2. What regulates the synthesis of serine? serine does... negative feedback at the level of 3-phosphoglycerate rxn level.

Hint 49

None

Front 50

1. How are Serine and Glycine related?

2. Besides hyrdroxymethyltransferase, what is needed to catalyze the rxn serine <-> glycine?

3. How many carbons do serine and glycine have?

4. what happens to the extra carbon atom?

5. What is an alternative method for glycine catabolism?

Back 50

1. Serine/threonine hydroxymethyltransferase rxn.

2. PLP

3. Serine =3C... Glycine = 2C

4. THF transfers the extra carbon to a 1-carbon unit

5. What is an alternative method for glycine catabolism? Glycine cleavage system: D-Amino acid oxidase (which releases NH4)

Hint 50

None

Front 51

What is the major source of 1-unit carbons?

Back 51

serine

Front 52

How are serine and glycine related? (hint: which enzyme) What is also required in this rxn?

Back 52

a) serine/threonine hydroxymethyltransferase… b) PLP

Front 53

Show the pathway that links serine and threonine to glycine.

Back 53

serine <-> glycine <- threonine

Hint 53

None

Front 54

Serine has 3-carbons and glycine has 2-carbons, what happens to the extra carbon in the serine/threonine hydroxymethyltransferase rxn?

Back 54

THF will either donate or receive it

Front 55

PKU is caused by an unstable or absent PAH enzyme, or it is caused by a defective regeneration of THB by dihydrobipterin, or by a defective THB synthesis. If THB synthesis is defective, what is the treatment?

Back 55

administer THB

Front 56

What are some proposed causes of neural abnormalities seen in PKUics?

Back 56

a) deficient tyrosine in the brain… b) high phenylalanine levels alter distribution of metabolites… c) direct effects of phenylalanine

Front 57

When is the best time to check for PKU?

Back 57

1-6 weeks after birth

Front 58

What are the first two steps in BCAA catabolism?

Back 58

BCAA transaminase ... BCKA dehydrogenase

Front 59

(a) Which enzyme is deficient in maple syrup disease?

(b) ∂-KA dehydrogenases are much like pyrvate dehydrogenase, such that they are complexes, In maple syrup disease, what is the mutation that causes the disorder and at what part of the BCKA dehydrogenase complex?

(c) What is the role of the part of the complex?

(c) Biochemically, what is observed?

Back 59

(a) BCKA dehydrogenase

(b) Try is replaced by Asp on E1 part of complex.

(c) the decarbosylation and covalent bodn to thiamine pyrophosphate)

(d) rise in BCAA (Val, Leu, Iso)