Delidow - Synthetic Pathways (Amino Acids)

Question 1

What four major molecules are synthesized primarily from Amino Acids?

Answer 1

NO

Creatine

Glutathione

Heme

Question 2

What are the three major components of Glutathione?

What functional group “protects”?

Answer 2

Glutamate, Cysteine, Glycine

Cystine’s sulfur is key antioxidant

Question 3

How is glutathione synthesized?

What does it require?

Answer 3

Glutamate

+ (cysteine)

Glutamylcysteine

+ (glycine)

Glutathione

• Each addition requires ATP

Question 4

What does oxidized glutathione form?

How do you reduce it to it’s active form?

What can happen if not reduced?

Answer 4

Glutathione disulfide (two connected by cystine bridge)

Reduced by NADPH in Pentose Phosphate Pathway

If not re-activated, large impact on RBCs, hemolystic anemia can occur

Question 5

What amino acids does Creatine consist of?

How is it synthesized?

What is the methyl donor in the rxn?

Answer 5

Arginine, Glycine

(Amidinotransferase)

Guanidinoacetate

SAM (Methyltransferase)

Creatine

(Kinase)

Phosphocreatine

Methyl Donor = SAM

Question 6

How is nitric oxide synthesized?

Where is it synthesized?

Answer 6

Arginine +

2 Round: O₂ + NADPH

Synthesized on the spot for immediate action

Question 7

What are two amino acid neurotransmitters and where do they function?

Answer 7

1. Glutamate (brain)
2. Glycine (spinal cord)

Question 8

What neurotransmitters are derived from amino acids?

Answer 8

1. Catecholamines
2. Serotonin
3. Histamine

Question 9

What are most important types of transformation in synthesis of neurotransmitters?

Answer 9

Hydroxylation

Decarboxylation

Question 10

What is rate limiting step of Catecholamine synthesis?

Answer 10

Tyrosine Hydroxylase (THB)

Question 11

What is the order of synthesis of catecholamines, starting with amino acid reactants?

Answer 11

Phenylalanine -> Tyrosine (can start w/either)

I (**THB**)

DOPA

I (Decarboxylase)

Dopamine

I (Hydroxylase)

Norepinephrine

I (SAM)

Epinephrine

PT DD NE

Question 12

What amino acid is serotonin synthesized from?

How many steps?

Order of enzymes?

Answer 12

Tryptophan

2-steps

Hydroxylase, Decarboxylase

Question 13

What amino acid is histamine synthesized from?

How many steps?

Enzyme?

Answer 13

Histidine

1-step

Decarboxylase

Question 14

Two roles for histamine?

Answer 14

Allergies

Stomach Acid Regulation

Question 15

Functions of heme-containing proteins?

Answer 15

Carry O₂ (Hb/Mb)

Metabolizing Drugs (P450’s)

Making ATP (Cytochromes)

Question 16

What are four steps to heme synthesis?

Answer 16

1. 3x Condensations - Tetrapyrrole
2. Cyclization, Modification
3. Porphyrin + Iron

Question 17

What amino acid and reactant are used to synthesize heme?

What is the rate limiting enzyme?

What does it require?

How is it regulated?

Answer 17

Succinyl CoA + Glycine

delta-Aminolevulinate Synthase (ALA Synthase)

Requires Pyridoxal Phosphate (PxLP)

Activated: Low Hemin

Inhibited: High Hemin

Question 18

What molecules are combined to form first step in heme synth?

Answer 18

Aminolevulinic Acid (ALA)

Question 19

What steps to heme synthesis are lead (Pb) sensitive?

Answer 19

First, Last

Question 20

What are the general steps in heme synthesis?

Answer 20

1. Combine to molecules to form ring
2. Combine rings linearly
3. Cyclize linear ringed molecules

Question 21

What enzyme adds iron to heme?

What is special about this?

Answer 21

Ferrochelatase

Lead sensitive

Question 22

What determines clinical presentation of heme disorders?

Answer 22

What intermediates accumulate

Question 23

What do porphyrias early in heme synthesis lead to?

How can you treat these symptoms?

Answer 23

Increase: ALA, Porphobilinogen

Abdominal pain

Psychological disturbances

-

Treat with P-450 metabolized drugs

Question 24

What do porphyrias late in heme synthesis result in?

Answer 24

Increased: Tetrapyrole

Symptoms:

Skin photosensitivity (pyro=sun burns)

Question 25

What do all porphyrias result in?

Answer 25

**De-repression** of **ALA Synthase --** buildup of intermediates

Question 26

What is most common porphyria?

Answer 26

Acute Intermittent porphyria, blocks formation of linear tetrapyrrole

Question 27

Why do some porphyrias affect both neurovisceral and skin photosensitivity?

Answer 27

Hemin production is blocked in later stages, **negative feedback look NOT established by High Hemin**

Question 28

How would you treat porphyria?

Answer 28

Push **HEMIN** to shut down pathway and build-up of intermediates

Question 29

Lead Poisoning What enzymes does it affect? What is differency in adults and children?

Answer 29

Inhibits: **Ferrochelatase, ALA Dehydratase** Adults: Reversible, anemia, increased immature RBCs (reticulocytes) Children: **Irreversible,** motor/cognitive deficits, lead in bones

Question 30

What is source of 85% of heme breakdown for turnover?

Answer 30

Hb

Question 31

What is heme broken down into? Where is this transported to? How is it excreted?

Answer 31

Billiverdin I Bilirubin - Sent to **liver** bound to albumin - Forms **bile** Bile exreted in gut I (metabolized, two firms) 1. Urobilin (**yellow**) 2. Stercobilin (**brown**)

Question 32

What happens when bilirubin production exceeds excretion? What else can cause this?

Answer 32

Excess deposited in tissues - **JAUNDICE** **-** Blockage of bile duct, Sickle Cell anemia, liver damage, alcoholism, Rh Incompatability (babies)