Synthetic Pathways with Amino Acids

Question 1

What amino acid is needed for glutathione synthesis?

Answer 1

Cysteine, glutamate, glycine

Question 2

What is the function of glutathione reductase?

Answer 2

Reduction of Glutathione disulfide to glutathione

Uses NADPH

Question 3

What two amino acids are needed for creatine synthesis?

Answer 3

Arginine and Glycine

Question 4

What enzyme is responsible for synthesizing creatine and what does it require?

Answer 4

Methyltransferase

SAM

Question 5

What amino acid is needed for nitric oxide synthesis?

Answer 5

Arginine

Question 6

What is the function of Nitric oxide synthase?

Answer 6

Formation of NO and citrulline from arginine

Requires two reductions with NADPH

Question 7

What are two important transformations for the synthesis of neurotransmitters from amino acids?

Answer 7

Hydroxylation

Decarboxylation

Question 8

What is the rate-limiting step in catecholamine synthesis?

Answer 8

Tyrosine hydroxylase

Requires THB

Question 9

What amino acid is required for serotonin synthesis?

Answer 9

Tryptophan

Question 10

What two enzymes are required for serotonin synthesis?

Answer 10

Tryptophan hydroxylase - requires O2 and tetrahydrobiopterin

5-hydroxytryptophan decarboxylase

Question 11

What amino acid is required for histamine synthesis?

Answer 11

Histidine

Decarboxylase reaction

Question 12

What are three important functions of heme-containing proteins?

Answer 12

Carrying oxygen

Metabolizing drugs

Making ATP

Question 13

What is the function of delta-aminolevulinate synthase?

Answer 13

Condensation of succinyl CoA and glycine in heme biosynthesis

Rate-limiting step

Requires PLP

Question 14

How is delta-ALA-synthase regulated?

Answer 14

Inhibited by HEMIN - oxidized form of heme released when synthesis exceeds amount of apoprotein available

Stimulated by increased need for heme – more apoprotein made

Question 15

What are Porphyrias?

Answer 15

Disorders of heme biosynthesis

Most are inherited and dominant

Intermediate accumulation determines clinical presentation

Question 16

What are symptoms of porphyrias leading to accumulation of ALA and porphobilinogen?

Answer 16

Abdominal pain and psychological distrubances

Treatment with P-450 metabolized drugs

Question 17

What are symptoms of porphyrias leading to accumulation of tetrapyrrole intermediates?

Answer 17

Skin photosensitivity

Question 18

What two porphyrias cause neurovisceral symptoms?

Answer 18

Acute intermittent porphyria

ALA dehydratase deficiency porphyria

Question 19

How does lead poisoning affect heme biosynthesis?

Answer 19

Inhibits Ferrochelatase and ALA dehydratase

Question 20

What are symptoms of lead poisoning in adults?

Answer 20

Peripheral neuropathy (reversible), GI symptoms, anemia, increased reticulocytes

Question 21

What are symptoms of lead poisoning in children?

Answer 21

Encephalopathy, behavioral changes, motor and cognitive deficits (irreversible), deposition of lead in bones

Question 22

Where does heme breakdown occur and what is the source for most of it?

Answer 22

Macrophages and hepatocytes

Most comes from hemoglobin

Remainder comes from cytochromes and immature RBCs

Question 23

What is the product of heme breakdown?

Answer 23

Bilirubin

Question 24

How is bilirubin excreted from the liver?

Answer 24

Bilirubin is conjugated to two glucuronic acid molecules

Then actively transported into bile

Question 25

What happens to bilirubin when bile is excreted to the gut?

Answer 25

Metabolized to either urobilinogen or stercobilin

Urobilinogen can be reabsorbed

Question 26

What is the cause of jaundice?

Answer 26

Bilirubin production exceeds excretion, excess is deposited in the skin and sclera

Can be caused by hemolytic condition, obstruction of bile duct, or liver damage