Conversion of AAs to Specialized Products Flashcards
What are the 3 sources of our AA pool?
1) Diet
2) Actual body protein
3) Synthesis of non-essential AAs that we make
What is the most common porphyrin in humans?
Heme
What is a porphyrin?
Cyclic compounds that binds metal ions (usually Fe2+ or Fe3+)
What many roles does heme have?
Hemoglobin, myoglobin, cytochromes, cytochrome P450 monooxygenase system, catalase, NO synthase and peroxidase
What are the major sites of heme biosynthesis?
Liver and erythrocyte-producing cells of bone marrow
What specific AA do we use for the making of heme?
Glycine
-Glycine is combined w/ succinyl CoA
What is the most important, rate-limiting, committed step of the making of heme?
ALAS1
What is heme biosynthesis inhibited by?
Heme
What is the 2nd step of heme biosynthesis (ALA to Porphobilinogen) inhibited by?
Lead
What is the last enzyme of heme biosynthesis?
Ferrochelastase (mitochondrial enzyme)
-Protoporphyrin IX -> Heme (iron is just added to center with N’s pointing in attached to it)
What is the last step of heme biosynthesis inhibited by?
Lead
What is porphyrias?
Rare, inherited defects in heme synthesis -> accumulation and increased excretion of porphyrins or porphyrin precursors
How long does a RBC live? Where is it degraded?
120 days
-Degraded in liver and spleen
What is the first step of heme degradation?
An old heme is picked up by a macrophage in spleen -> Heme oxygenase breaks open the heme (using NADPH) -> Biliverdin (green pigment)
What happens to biliverdin?
Reduced to bilirubin (red-orange) by biliverdin reductase (using NADPH)
What happens to bilirubin?
It is too hydrophobic, so attaches to albumin -> complex travels to liver
What happens to the bilirubin in the liver in order to make it more soluble and easier to eliminate?
A conjugation adds 2 acidic sugars (UDP-glucuronic acid) to bilirubin to form bilirubin diglucoronide
What gives urine its yellow color?
As bile goes through the intestine, bacteria deconjugates it -> urobilinogen in colon -> some goes to kidney -> urobilin
What gives feces its brown color?
Rest of urobilinogen in colon becomes oxidized by intestinal bacteria -> stercobilin
What is hyperbilirubinemia?
High [bilirubin] in blood -> Yellow color of skin, nail beds and sclerae
Why are premature babies more likely to get jaundice?
Have less of Bilirubin UDP-glucuronosyltransferase (bilirubin UGT) -> enzyme that makes bilirubin more soluble by conjugation
- Serum levels of bilirubin will be too high
- Tx: UV light has direct impact on bilirubin (modifies it to make it more soluble)
What are 5 other N-containing compounds?
1) Catecholamines
2) Histamine
3) Serotonin
4) Creatine
5) Melanin
What are the catecholamines?
Dopamine, Norepinephrine, Epinephrine
-All biologically active amines
What are the catecholamines made from?
Tyrosine
