31-AMINO ACID METABOLISM LECTURE 4-5 – Dr. Venk

Question 1

Name two linear compounds in the praline biosynthetic pathway.

Answer 1

Glutamate and glutamate semialdehyde

Question 2

What are the functions of hydroxyprolines.

Answer 2

key role for collagen stability and structural components

Question 3

Name the amino acid that is required for selenocysteinyl tRNA sysnthesis.

Answer 3

Selenocysteine

Question 4

What is the cofactor that is required for the phenylalanine hydroxylase reaction.

Answer 4

Tetrahydrobiopterin (THB)

Question 5

What enzyme deficiency causes phenylketonuria?

Answer 5

Phenylalanine hydroxylase

Question 6

Name two disorders of tyrosine metabolism.

Answer 6

phenylkaptonuria, and alcaptonuria

Question 7

What enzyme defiency causes albinism?

Answer 7

Tyrosinase

Question 8

Methionine adenosyltransderase catalyzes the synthesis of _____?

Answer 8

SAM (S-adenosylmethionine)

Question 9

What compound is the precursor for cysteine synthesis?

Answer 9

Methionine

Question 10

Name a disorder of cysteine metabolism.

Answer 10

Homocystinuria & cystathionuria

Both have “cyst” in it!

Question 11

Name the oxidized form of homocysteine.

Answer 11

Homocystine

Question 12

Name the amino acid precursor for NMP synthesis.

Answer 12

Tryptophan

Question 13

Name an enzyme that requires a vitamin B12 derivative as a coenzyme.

Answer 13

Methionine synthase and methymalonyl mutase

Question 14

Name the pathway that requires both the derivatives of vitamin B12 as a coenzyme.

Answer 14

Resynthesis of methionine:

methylmalonyl CoA –> succinyl CoA

Question 15

Name a disorder of branched chain amino acid metabolism.

Answer 15

Maple syrup urine disease

Question 16

Name the amino acid that is required for carnitine biosynthesis.

Answer 16

Lysine

Question 17

Name the two amino acids that are required for creatine biosynthesis.

Answer 17

Glycine and arginine

Question 18

Name the components of folate.

Answer 18

Pterin, PABA and glutaminc acid

which result in
Pteridine Ring and Polyglutamate

Question 19

Name 2 active centers of tetrahydrofolate.

Answer 19

N5 and N10

Question 20

Name the three reactions that use tetrahydrofolate.

Answer 20

Purine, thymidine and methionine synthesis

Question 21

Name the amino acid and the vitamin derivative that is required for glycine synthesis.

Answer 21

Serine and THF (?)

Question 22

Name the two degradative pathways that require tetrahydrofolate.

Answer 22

○ homocysteine → methionine

○ Histidine → glutamate

Question 23

Name two reactions that require tetrahydrobiopterin as a cofactor.

Answer 23

1) Phenylalanine metabolism to tyrosine (tyrosine hydroxylase)
2) 5-hydroxytryptophan from tryptophan in synthesis of seratonin (tryptophan hydroxylase)

Question 24

Describe how homocysteine is converted into methionine.

Answer 24

Methionine synthase + vit B12
Homocysteine ————–> Methionine
N5-CH3-THF

Question 25

Lysine is required for the synthesis of _____

Answer 25

Carnitine, Acetyl CoA and ketone bodies

Question 26

Name the vitamin derivative that is required for prolyl hydroxylase reaction.

Answer 26

Vitamin C

Question 27

Why is the element selenium essential?

Answer 27

Selenium is essential to normal metabolism because it is necessary in the formation of Selenocysteine. Selenocysteine is needed to make glutathione peroxidases among other various selenoproteins. Selenocysteine is also used in the synthesis of selenocysteinyl-tRNA.

Question 28

Describe in detail, the pathway for the biosynthesis of SAM and cysteine

Answer 28

SAM: methionine + ATP –> SAM + P_i + PP_i (via methionine adenosyltransferase (MAT) )

Cysteine: Cystathionine —> Cysteine + alpha-ketobutyrate (via gamma Cystathionase and cofactor Pyridoxal Phosphate [Vit B6 derivative])

–

The biosynthesis of SAM involves the substrates Methionine and ATP. The enzyme that catalyzes the reaction is Methionine Adenosyltransferase.

SAM is then converted to S-adenosylhomocysteine, catalyzed by Methyltransferase. S-adenosylhomocysteine is converted to Homocysteine, losing its adenosine group. Homocysteine is converted to Cystathionine. This reaction requires the enzyme Cystathionine Beta Synthase and Pyridoxal Phosphate (vitamin B6). Cystathionine is then converted to Cysteine and this reaction is catalyzed by Gamma Cystathionase and also requires Pyridoxal Phosphate (vitamin B6).

Question 29

Describe in detail the biochemical basis for phenylketonuria

Answer 29

Phenylalanine is converted to Tyrosine via the enzyme Phenylalanine Hydroxylase. The reaction also requires THB. Deficiency of this enzyme results in increased levels of Phenylalanine and this is excreted in the urine as phenylpyruvate and phenylketones. In some cases, deficiency of THB also causes PKU. Since tyrosine is no longer formed, those compounds that are related to tyrosine are also blocked in individuals with PKU

Question 30

Describe in detail the biochemical basis for alkaptonuria

Answer 30

Tyrosine is degraded into p-hydroxy phenylpyruvate. This is converted to Homogentisate via an oxidase. The Homogentisate is converted to Maleyl Acetoacetate via another oxidase. Deficiency of the Homogentisate Oxidase results in accumulation of Homogentisate or homogentisic acid. This compound is oxidized into a dark brown polymer and is deposited in joints, which causes arthritis.

Question 31

Describe in detail the biochemical basis for albinism

Answer 31

Tyrosine through a series of reactions is also converted into Melanin. Involved in these reactions is the enzyme Tyrosinase. Melanin is responsible for skin pigmentation. In individuals with albinism, tyrosinase deficiency results in low melanin production, and the skin the becomes susceptible to the damaging effects of sunlight such as skin cancer.

Question 32

Describe in detail, the biochemical basis for the diseases:

a. homocystinuria
b. cystathionuria
c. cystinuria

Answer 32

All three of these diseases involve the following reaction:
Methionine is converted to SAM. SAM is converted to S-adenosylhomocysteine, which is converted to Homocysteine. Homocysteine is converted to Cystathionine via Cystationine Beta Synthase and Pyridoxal Phosphate. Cystathionine is converted to Cysteine via Gamma Cystathionase and Pyridoxal Phosphate.

a. Cystathionine Beta synthase deficiency causes homocysteine accumulation. Pyridoxal Phosphate deficiency can make the problem worse.
b. Caused by deficiency of the next enzyme involved in the pathway: Gamma Cystathionase. The accumulated Cystathionine is then excreted. This condition can also result from a deficiency of Pyridoxal Phosphate (vitamin B6). This disease is less problematic than Homocystinuria.
c. Cystinuria is due to a defect in membrane transport of dietary cysteine through epithelial cell membrane which results in the accumulation of cysteine in the urine. Cysteine gets oxidized into Cystine. Cystine has low solubility, so it precipitates out in the urinary tract forming kidney stones.

Question 33

Describe in detail the biochemical basis for cystinuria

Answer 33

defect in epithelial membrane transporter of dietary cysteine. Cysteine nonezymatically gets oxidized to cystine. Cystine precipitates into kidney stones

Question 34

Describe in detail the biochemical basis for maple syrup urine

Answer 34

Leucine is converted into Acetyl CoA via the enzyme Branched Chain Ketoacid Dehydrogenase. Valine and Isoleucine are converted into Propionyl CoA via the same enzyme. Deficiency in this enzyme causes MSUD.

Question 35

Describe in detail the biochemical basis for histidinemia

Answer 35

b. Histidine metabolism involves the conversion of Histidine to Urocanate via the enzyme Histidase. Uroconate is then converted to Glutamate through a series of reactions.

Histidinemia is due to deficiency of the enzyme histidase. This enzyme is highly expressed in skin and liver. Therefore histidase deficiency can be confirmed using skin biopsies. As a side note, urocanate is a component of sweat.

Question 36

Can folic acid be synthesized by humans?

Answer 36

No

Question 37

What step is inhibited by sulfamethoxazole?

Answer 37

It inhibits the formation of Folic Acid from ParaAmino Benzoic Acid (PABA). This is the first step in the pathway to convert PABA to THF.

Question 38

Describe in detail the role of folate in relation to one carbon metabolism

Answer 38

Folate is converted to THF. One carbon units from amino acid degradation are added on to THF to form active folate. Active folate comes in three forms: Formyl THF, Methenyl THF, and Methylene THF. These all serve as a carrier for carbon atoms. They can be reduced to Methyl THF which is utilized in the conversion of Homocysteine to Methionine, and in so doing reforms THF. Formyl and Methylene THF are involved in Purine synthesis, Methylene THF is involved in Thymidine synthesis, and Methyl THF is involved in Methionine synthesis

Question 39

Describe the biosynthesis of carnitine

Answer 39

Lysine is converted to N-trimethyl Lysine. This reaction is catalyzed by Methyl Transferase and 3 [SAM]. N-trimethyl Lysine is converted to Carnitine through a number of steps that Venk did not detail

Question 40

What are some organism specific dihydrofolate reductase inhibitors?

Answer 40

methotrexate, Pyrimethamine, and epiroprim/Trimethoprim

Question 41

Trimethoprim, methotrexate, and pyrimethamine inhibits _______,______, and ________ (specify the organisms).

Answer 41

Trimethoprim inhibits bacterial DHFF

Methotrexate inhibits Eukaryotes

Pyrimethamine inhibits Protozoans (amoebas)

Question 42

Patients with homocystinuria lack

a) cystathionine synthase
b) prolyl hydroxylase
c) methionine adenosyltransferase
d) methylmalonyl coA mutase
e) all the answers are correct

Answer 42

a) cystathionine synthase