MMT: iron and hemochromatosis Flashcards
What are inborn errors of metabolism?
Genetic disorders where a single gene defect can affect one or more steps in a metabolic process.
What is typically impacted in inborn errors of metabolism? What is the issue with this?
Enzymes and transporters; this can lead to accumulation or inability to synthesize, both of which can cause issues.
What is HCP1?
Transports heme iron into duodenal enterocytes.
What is heme oxidase?
An enzyme that releases iron from heme in enterocytes.
What is true of non-heme iron in terms of absorption?
It can only be absorbed into enterocytes in the ferrous state.
What is DMT1?
Transports non-heme Fe 2+ into enterocytes.
What is DCYTB?
Brush border enzyme that reduces Fe 3+ to Fe 2+.
What does ferroportin do?
Transports Fe 2+ across the basolateral membrane and into the blood.
What is transferrin?
A protein that carries iron circulating in the blood in its monoferric or diferric form.
What is true of serum ferritin?
It correlates with total body iron stores, meaning higher serum ferritin indicates more iron in the body.
What is TfR1?
The transporter for transferrin.
What can ferritin do in cells?
Act as a storage site for iron.
What does hepcidin do?
It binds to ferroportin in the blood, leading to endocytosis of ferroportin, preventing iron release from the cell into the blood.
Describe the activation of hepcidin.
- Diferric holo-transferrin binds TfR1.
- HFE interacts with TfR2, initiating a signaling complex.
- The complex phosphorylates SMAD pathway, activating HAMP gene.
- HAMP gene increases production and secretion of hepcidin.
What is the most common mutation in hemochromatosis type 1?
HFE gene.
Briefly describe the mechanism of hemochromatosis type 1.
Loss of HFE function reduces production of hepcidin, hindering the ability to regulate iron release into the blood.
What is the basic outcome of hemochromatosis type 1?
Iron in the blood saturates transferrin and iron accumulates in the liver and other organs.
Who is most likely to get hemochromatosis?
50 year old white males.
What in the diet may aid hemochromatosis?
Vitamin C.
Transferrin saturation of ___ indicates hemochromatosis.
50%.
How can we do genetic testing for hemochromatosis?
PCR using sequence specific primers to amplify a mutated allele.
