Chapter 29

Question 1

What is the precursor/substrate for synthesizing proline?

Answer 1

Glutamate

Question 2

Proline synthesis steps/enzymes (NOT HY)

Answer 2

Step 1: uses ATP, NADH
Step 2: spontaneous
Step 3: uses NADPH and enzyme

Question 3

What is needed for the hydroxylation of proline? (HY)

Answer 3

VITAMIN C (ascorbic acid), proline hydroxylase

proline hydroxylase requires vitamin C

Question 4

What is the use of 3- or 4-hydroxyproline?

Answer 4

they are major components of collagen and help with collagen stability (connective tissue)

Question 5

what causes scurvy? What is one symptom? (HY)

Answer 5

Scurvy is caused by a deficiency of ascorbate (Vit C). Without this, hydroxyproline cannot be synthesized resulting in collagen issues.

Symptom: Scorbutic tongue/bleeding gums

Question 6

What substrates are needed for selenocysteinyl-tRNA synthesis?

Answer 6

Substrates: seryl-tRNA, selenide**, ATP


Question 7

What is selenocysteinyl-tRNA used to make?

Answer 7

It produces selenoproteins like…

1. **Glutathione peroxidase: Prevents oxidative damage
2. Deiodinases: convert T4 —> T3 (active form)
3. Thioredoxin reductase

Question 8

what does phenylalanine hydroxylase (PAH) do? What does it require?

Answer 8

Converts phenylalanine into tyrosine (Phenylalanine metabolism)

Requires: THB (Tetrahydrobiopterin), O2

Question 9

What is phenylketonuria (PKU) and it’s pattern of inheritance? What accumulates?

Answer 9

phenylketonuria (PKU): inability to metabolize phenylalanine. Causes an accumulation of phenylalanine, phenylpyruvate and phenyllactate

AUTOSOMAL RECESSIVE: if mom and dad are unaffected carriers, 1/4 chance of child having it

Question 10

What are the symptoms of PKU?

Answer 10

symptoms: Mousy/musty odor***, Light pigmentation, peculiar gait/stance, eczema, developmental delay, low IQ, epilepsy

Question 11

what causes classical PKU and what is the treatment?

Answer 11

Cause: PAH deficiency
Tx: Low phenylalanine, high tyrosine diet

Question 12

What causes nonclassical PKU? And what is the treatment?

Answer 12

cause: THB deficiency (cofactor)
tx: THB supplements (kuvan/sapropterin), large neutral AA’s

Question 13

tyrosine metabolism steps/enzymes

Answer 13

Question 14

A deficiency in what enzyme causes alkaptonuria? What compound accumulates and what is the result of this accumulation?

Answer 14

homogentisate oxidase deficiency causes alkaptonuria (“Black urine disease”)

Homogentisate accumulates and forms dark brown polymers. Causes arthritis and dark urine

Question 15

what is the first step in methionine metabolism/cysteine synthesis (substrates, enzyme, product)?

Answer 15

substrates: Methionine, ATP
product: S-adenosylmethionine (SAM)

Enzyme: methionine adenosyltransferase (MAT)

Question 16

what is the importance of SAM?

Answer 16

a universal methyl group donor

Question 17

What products are made via SAM dependent methylation of the following methyl group acceptors…

1. guanidoaceitic acid
2. protein bound lysine
3. histones
4. DNA

Answer 17

1. Creatine phosphate: stores the phosphate from ATP in muscle/cardiac tissue and brain to be used later to make ATP from ADP
2. Trimethyl lysine: Used for carnitine synthesis. Carnitine is added onto fatty acids so they can move into mitochondria for beta oxidation
3.  Methylated lysine/arginine** of histones: typically inactivates chromatin. enzyme: Methyl transferase
4. CpG islands: methylated DNA typically shuts off gene expression
   

Question 18

 what enzyme converts homocysteine to cystathionine? What cofactors/substrates are needed?

Answer 18

Enzyme: cystathionine beta-synthase
Requires: SERINE AND PYRIDOXAL PHOSPHATE (B6)

Question 19

what enzyme is used to convert cystathionine to cysteine? What cofactor is needed?

Answer 19

Enzyme: gamma-cystathionine
cofactor: pyridoxal phosphate (B6)

Question 20

What is homocystinuria and what is it caused by?

Answer 20

Homocystinuria: The accumulation of homocysteine and methionine in the blood AND homocysteine in the urine

Caused by deficiencies in any of the following: cystathionine B-synthase (CBS), pyridoxal phosphate (B6), methionine synthase, B12

Question 21

What can cause atheromas/atherosclerosis by forming a very reactive intermediate that thiolates LDL?

Answer 21

Homocysteine (homocystinuria): forms homocysteinethiolactone (reactive)

Question 22

Substrate and enzyme involved in methionine resynthesis?

Answer 22

Substrate: homocysteine
Enzyme: homocysteine methyltransferase AKA methionine synthase
cofactor: N5-CH3-tetrahydrofolate

Question 23

what is caused by a deficiency in gamma-cystathionase or its cofactor (B6)?

Answer 23

Cystathionuria: excess cystathionine, Can’t be converted into cysteine

Question 24

What is caused by a defect in membrane transport of dietary cysteine through the epithelial cell?

Answer 24

Cystinuria: instead of being transported cysteine is oxidized to cystine OR homocystine (disulfide bond). Cystine has poor solubility and precipitates in the urinary tract to form KIDNEY STONES

Question 25

What are the starting substrates and products of methionine degradation?

Answer 25

**also called cysteine synthesis

substrates: methionine, ATP
Products: cysteine, alpha-ketobutyrate (—> propionyl CoA)