Chapter 29 Flashcards
What is the precursor/substrate for synthesizing proline?
Glutamate
Proline synthesis steps/enzymes (NOT HY)
Step 1: uses ATP, NADH
Step 2: spontaneous
Step 3: uses NADPH and enzyme
What is needed for the hydroxylation of proline? (HY)
VITAMIN C (ascorbic acid), proline hydroxylase
proline hydroxylase requires vitamin C
What is the use of 3- or 4-hydroxyproline?
they are major components of collagen and help with collagen stability (connective tissue)
what causes scurvy? What is one symptom? (HY)
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
What substrates are needed for selenocysteinyl-tRNA synthesis?
Substrates: seryl-tRNA, selenide**, ATP

What is selenocysteinyl-tRNA used to make?
It produces selenoproteins like…
- **Glutathione peroxidase: Prevents oxidative damage
- Deiodinases: convert T4 —> T3 (active form)
- Thioredoxin reductase
what does phenylalanine hydroxylase (PAH) do? What does it require?
Converts phenylalanine into tyrosine (Phenylalanine metabolism)
Requires: THB (Tetrahydrobiopterin), O2
What is phenylketonuria (PKU) and it’s pattern of inheritance? What accumulates?
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
What are the symptoms of PKU?
symptoms: Mousy/musty odor***, Light pigmentation, peculiar gait/stance, eczema, developmental delay, low IQ, epilepsy
what causes classical PKU and what is the treatment?
Cause: PAH deficiency
Tx: Low phenylalanine, high tyrosine diet
What causes nonclassical PKU? And what is the treatment?
cause: THB deficiency (cofactor)
tx: THB supplements (kuvan/sapropterin), large neutral AA’s
tyrosine metabolism steps/enzymes
A deficiency in what enzyme causes alkaptonuria? What compound accumulates and what is the result of this accumulation?
homogentisate oxidase deficiency causes alkaptonuria (“Black urine disease”)
Homogentisate accumulates and forms dark brown polymers. Causes arthritis and dark urine
what is the first step in methionine metabolism/cysteine synthesis (substrates, enzyme, product)?
substrates: Methionine, ATP
product: S-adenosylmethionine (SAM)
Enzyme: methionine adenosyltransferase (MAT)
what is the importance of SAM?
a universal methyl group donor
What products are made via SAM dependent methylation of the following methyl group acceptors…
- guanidoaceitic acid
- protein bound lysine
- histones
- DNA
- Creatine phosphate: stores the phosphate from ATP in muscle/cardiac tissue and brain to be used later to make ATP from ADP
- Trimethyl lysine: Used for carnitine synthesis. Carnitine is added onto fatty acids so they can move into mitochondria for beta oxidation
-  Methylated lysine/arginine** of histones: typically inactivates chromatin. enzyme: Methyl transferase
- CpG islands: methylated DNA typically shuts off gene expression

 what enzyme converts homocysteine to cystathionine? What cofactors/substrates are needed?
Enzyme: cystathionine beta-synthase
Requires: SERINE AND PYRIDOXAL PHOSPHATE (B6)
what enzyme is used to convert cystathionine to cysteine? What cofactor is needed?
Enzyme: gamma-cystathionine
cofactor: pyridoxal phosphate (B6)
What is homocystinuria and what is it caused by?
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
What can cause atheromas/atherosclerosis by forming a very reactive intermediate that thiolates LDL?
Homocysteine (homocystinuria): forms homocysteinethiolactone (reactive)
Substrate and enzyme involved in methionine resynthesis?
Substrate: homocysteine
Enzyme: homocysteine methyltransferase AKA methionine synthase
cofactor: N5-CH3-tetrahydrofolate
what is caused by a deficiency in gamma-cystathionase or its cofactor (B6)?
Cystathionuria: excess cystathionine, Can’t be converted into cysteine
What is caused by a defect in membrane transport of dietary cysteine through the epithelial cell?
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
What are the starting substrates and products of methionine degradation?
**also called cysteine synthesis
substrates: methionine, ATP
Products: cysteine, alpha-ketobutyrate (—> propionyl CoA)
