Delidow - Synthetic Pathways (Amino Acids) Flashcards
What four major molecules are synthesized primarily from Amino Acids?
NO
Creatine
Glutathione
Heme
What are the three major components of Glutathione?
What functional group “protects”?
Glutamate, Cysteine, Glycine
Cystine’s sulfur is key antioxidant
How is glutathione synthesized?
What does it require?
Glutamate
+ (cysteine)
Glutamylcysteine
+ (glycine)
Glutathione
- Each addition requires ATP
What does oxidized glutathione form?
How do you reduce it to it’s active form?
What can happen if not reduced?
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
What amino acids does Creatine consist of?
How is it synthesized?
What is the methyl donor in the rxn?
Arginine, Glycine
(Amidinotransferase)
Guanidinoacetate
SAM (Methyltransferase)
Creatine
(Kinase)
Phosphocreatine
Methyl Donor = SAM
How is nitric oxide synthesized?
Where is it synthesized?
Arginine +
2 Round: O2 + NADPH
Synthesized on the spot for immediate action
What are two amino acid neurotransmitters and where do they function?
- Glutamate (brain)
- Glycine (spinal cord)
What neurotransmitters are derived from amino acids?
- Catecholamines
- Serotonin
- Histamine
What are most important types of transformation in synthesis of neurotransmitters?
Hydroxylation
Decarboxylation
What is rate limiting step of Catecholamine synthesis?
Tyrosine Hydroxylase (THB)
What is the order of synthesis of catecholamines, starting with amino acid reactants?
Phenylalanine -> Tyrosine (can start w/either)
I (**THB**)
DOPA
I (Decarboxylase)
Dopamine
I (Hydroxylase)
Norepinephrine
I (SAM)
Epinephrine
PT DD NE
What amino acid is serotonin synthesized from?
How many steps?
Order of enzymes?
Tryptophan
2-steps
Hydroxylase, Decarboxylase
What amino acid is histamine synthesized from?
How many steps?
Enzyme?
Histidine
1-step
Decarboxylase
Two roles for histamine?
Allergies
Stomach Acid Regulation
Functions of heme-containing proteins?
Carry O2 (Hb/Mb)
Metabolizing Drugs (P450’s)
Making ATP (Cytochromes)
What are four steps to heme synthesis?
- 3x Condensations - Tetrapyrrole
- Cyclization, Modification
- Porphyrin + Iron
What amino acid and reactant are used to synthesize heme?
What is the rate limiting enzyme?
What does it require?
How is it regulated?
Succinyl CoA + Glycine
delta-Aminolevulinate Synthase (ALA Synthase)
Requires Pyridoxal Phosphate (PxLP)
Activated: Low Hemin
Inhibited: High Hemin
What molecules are combined to form first step in heme synth?
Aminolevulinic Acid (ALA)
What steps to heme synthesis are lead (Pb) sensitive?
First, Last
What are the general steps in heme synthesis?
- Combine to molecules to form ring
- Combine rings linearly
- Cyclize linear ringed molecules
What enzyme adds iron to heme?
What is special about this?
Ferrochelatase
Lead sensitive
What determines clinical presentation of heme disorders?
What intermediates accumulate
What do porphyrias early in heme synthesis lead to?
How can you treat these symptoms?
Increase: ALA, Porphobilinogen
Abdominal pain
Psychological disturbances
-
Treat with P-450 metabolized drugs
What do porphyrias late in heme synthesis result in?
Increased: Tetrapyrole
Symptoms:
Skin photosensitivity (pyro=sun burns)
What do all porphyrias result in?
De-repression of ALA Synthase – buildup of intermediates
What is most common porphyria?
Acute Intermittent porphyria, blocks formation of linear tetrapyrrole
Why do some porphyrias affect both neurovisceral and skin photosensitivity?
Hemin production is blocked in later stages, negative feedback look NOT established by High Hemin
How would you treat porphyria?
Push HEMIN to shut down pathway and build-up of intermediates
Lead Poisoning
What enzymes does it affect?
What is differency in adults and children?
Inhibits:
Ferrochelatase, ALA Dehydratase
Adults: Reversible, anemia, increased immature RBCs (reticulocytes)
Children: Irreversible, motor/cognitive deficits, lead in bones
What is source of 85% of heme breakdown for turnover?
Hb
What is heme broken down into?
Where is this transported to?
How is it excreted?
Billiverdin
I
Bilirubin
- Sent to liver bound to albumin
- Forms bile
Bile exreted in gut
I (metabolized, two firms)
- Urobilin (yellow)
- Stercobilin (brown)
What happens when bilirubin production exceeds excretion?
What else can cause this?
Excess deposited in tissues - JAUNDICE
- Blockage of bile duct, Sickle Cell anemia, liver damage, alcoholism, Rh Incompatability (babies)
