Protein Biochemistry 3

Question 1

Sulfur-containing amino acids

Answer 1

cysteine (non-essential) and methionine (essential)

Question 2

This amino acid can form disulfides, important for structural integrity of extracellular proteins (hormones, cytokines, receptors)

Answer 2

cysteine

Question 3

Methionine

Answer 3

essential amino acid used to produce S-adenosylmethionine (intermediate in the production of cysteine)

Question 4

Function of SAM

Answer 4

produced in the first step of methionine degradation –> S-adenosylhomocysteine (SAH)

major carbon donor and a “high energy storage unit” like ATP

Question 5

Methionine recycling reactions

Answer 5

Met (SAM synthase) –> SAM (methyltransferase) –> SAH (remove adenosine) –> homocysteine –> Met

need THF and vitamin B12 to convert homocysteine back to Met

Met –> SAM –> SAH –> homocysteine (cystathione B-synthase) –> cystathione (cystathione gamma-lyase) –> cysteine

Question 6

Hyperhomocysteinemia

Answer 6

high homocysteine –> multiple problems including cardiovascular disease.

Due to low folate, B6 (PLP) and B12. Cysteine becomes essential. Treat with vitamin replacement

Question 7

Homocysteinuria

Answer 7

defect in cystathionine-b-synthase (CBS) –> cannot convert homocysteine to cystathionine

leads to mental retardation, osteoporosis and autoimmune vascular disease

treat with B6 replacement –> “force” CBS activity

Question 8

cysteinuria

Answer 8

kidney stones (renal failure) due to defective transporter of cysteine (and ornithine, lysine, arginine). leads to crystallization in urea

treatment: acetazolamide –> soluble cysteine

Question 9

cofactors used for transferring carbons

Answer 9

SAM, THF

Question 10

Function of glutathione

Answer 10

redox buffer. thiol buffer action maintains proteins in their reduced forms (intracellular proteins) and regulates activity (enzymes)

cofactor for several enzymes (glutathione transferase, GST)

reduce hydrogen peroxide to water. general protection against ROS

keep Fe2+ in the reduced state so it can continue binding O2

Question 11

Trp metabolism

Answer 11

metabolized to glucogenic (pyruvate –> acetyl CoA) or ketogenic (acetoacetyl CoA) products
1. hydroxylated by tryptophan hydroxylase using BH4 as a cofactor

Question 12

importance of Tryptophan

Answer 12

used to produce serotonin, melatonin, and niacin

Question 13

Phenylalanine and tyrosine metabolism

Answer 13

metabolized to fumarate or acetoacetate

Phe is hydroxylated by phenylalanine hydroxylase (BH4 cofactor) –> tyrosine –> hydrozylated by tyrosine hydroxylase (BH4 cofactor) –> DOPA –> catecholamines, melanin

tyrosine also converted to fumarate and acetoacetate

Question 14

Metabolic diseases of tyrosine metabolism

Answer 14

PKU (defect in phenylalanine hydroxylase) –> buildup of phenyllactate, phenylacetate, and phenylpyruvate

Tyrosinemias = defects in tyrosine degradation

Question 15

Function of THF

Answer 15

essential for synthesis of amino acids and nucleic acids

Question 16

Synthesis of THF

Answer 16

folic acid + NADPH + (dihydrofolate reductase) –> dihydrofolate + (NADPH, DHFR) –> tetrahydrofolate

methotrexate –| DHFR –> blocked THF synthesis