Loading in 2 Seconds...
Loading in 2 Seconds...
Pathophysiology of Heme Synthesis Beth A. Bouchard BIOC 212: Biochemistry of Human Disease Spring 2006. HEME-CONTAINING PROTEINS Hemoglobin Myoglobin Cytochromes Catalase Some peroxidases. STRUCTURE OF HEME. An Overview of Iron Metabolism.
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Beth A. Bouchard
BIOC 212: Biochemistry of Human Disease
Electron, oxygen transport
Sensor of Fe, ROS
Formation of protein-bound radicals
Storage and Sequestration: Ferritin
Toxicity: Oxidative stress
** Amino acid (building blocks of protein) synthesized in your body
Reduced initiation of translation
In RBCS, heme synthesis is also regulated at the level of the en-zymes ferrochelatase* and porphobilinogen deaminase**
Regulated at level of ALA synthase: Formation of 5-ALA is the rate-limiting step in heme synthesis in the liver
5-ALA is formed in the mitochondria and transported
to the cytoplasm
Level of enzyme synthesis
Enzyme synthesis, as well as its transport to the mitochondria, is inhibited by elevated levels of heme and hemin, the Fe3+ oxidation product of heme
Enzyme synthesis is upregulated by a large number of drugs including barbiturates, steroids with a 4,5 double bond (e.g. testosterone) and some oral contraceptives: These drugs are metabolized by the microsomal cytochrome P450 mono-oxygenase system, a heme- containing protein.
Level of enzyme activity
Heme and hemin inhibit ALA synthase activity
Requires pyridoxal phosphate (Vitamin B6) as a coenzyme
Irritibility Poor appetite
Lethargy Abdominal pain (with or
Sleeplessness without vomiting)
Binds to any compound with a sulfhydryl group
Inhibits multiple enzyme reactions including those involved in heme biosynthesis (PBG synthase & ferrochelatase)
One symptom of lead toxicity is increases in 5-ALA without concomitant increases in PBG
Scriver et al., The Metabolic & Molecular Basis of Inherited Disease, 8th edition, 2001.
deaminase, which is involved in the conversion of
porphobilinogen (PBG) to uroporphyrinogen III
and the urine
abdominal pain (neurovisceral)
decarboxylase, which is involved in the conversion of
uroporphyrinogen III to coproporphyrinogen III