Hepcidin and Iron Metabolism

Questions and Answers

Which of the following factors does NOT directly stimulate the synthesis of hepcidin?

Bone morphogenetic protein 6 (BMP6)

Diferric transferrin

Matriptase 2 (TMPRSS6) (correct)

Transferrin receptor 2 (TFR2)

In the context of iron deficiency, how does the absence of diferric transferrin affect hepcidin synthesis?

It prevents the formation of the signaling complex involving TFR2, HJV, and HFE, reducing hepcidin synthesis. (correct)

It stimulates matriptase 2 activity, indirectly promoting hepcidin synthesis.

It causes TFR1 to bind to HFE, leading to enhanced hepcidin synthesis.

It leads to increased BMP synthesis, resulting in higher hepcidin levels.

What is the primary function of hepcidin in iron homeostasis?

To inhibit iron release from storage sites. (correct)

To promote iron absorption from the intestines.

To stimulate the production of red blood cells.

To increase iron utilization by cells.

Which of the following is NOT a consequence of elevated hepcidin levels?

Increased iron release from macrophages. Signup and view all the answers

How does the interaction between diferric transferrin and transferrin receptor 2 (TFR2) contribute to hepcidin synthesis?

It stabilizes TFR2 on the cell membrane, facilitating the formation of the signaling complex. Signup and view all the answers

Which factor predominantly favors the absorption of iron in the human body?

Hydrochloric acid Signup and view all the answers

What is the role of erythroferrone in relation to hepcidin secretion?

Inhibits BMP-mediated signaling for hepcidin secretion Signup and view all the answers

Which of these conditions is likely to result in high levels of plasma hepcidin?

Inflammation due to interleukin 6 (IL-6) Signup and view all the answers

How is iron absorption regulated in the enterocyte after dietary intake?

By altering levels of DMT-1 and ferroportin Signup and view all the answers

What is a significant consequence of ineffective erythropoiesis on iron metabolism?

Low plasma hepcidin despite iron overload Signup and view all the answers

Study Notes

Hepcidin Overview

Hepcidin is a liver-produced polypeptide and major hormonal regulator of iron homeostasis.
It inhibits iron release from macrophages, intestinal epithelial cells, and other cells by interacting with ferroportin, a transmembrane iron exporter.
Elevated hepcidin levels reduce both iron absorption and release from macrophages.

Control of Hepcidin Expression

Hepcidin synthesis is influenced by factors such as iron status, cytokines during inflammation, erythropoiesis, and hypoxia.
In iron overload, high plasma hepcidin levels are maintained via differentiation in liver sinusoidal cells stimulated by diferric transferrin.
Bone morphogenetic proteins (BMPs), particularly BMP6, bind to BMPRs on liver cells, enhancing hepcidin synthesis through signaling proteins SMADs.
In iron deficiency, reduced levels of diferric transferrin lead to decreased BMP synthesis, refusal of Hepcidin synthesis, and subsequent iron overload in cases of ineffective erythropoiesis.

Factors Affecting Hepcidin

Erythroblasts release erythroferrone, suppressing BMP-mediated signaling, resulting in low hepcidin levels during increased erythroblast activity.
Hypoxia inhibits hepcidin synthesis, while inflammation (via IL-6 and other cytokines) stimulates hepcidin production to lower plasma iron and inhibit bacterial growth.

Dietary Iron Sources

Iron is present in food as ferric hydroxides and protein complexes, with meat (especially liver) providing better absorption than vegetables or dairy.
A typical Western diet contains 10-15 mg of iron daily, with only 5-10% absorption, increased to 20-30% during pregnancy or deficiency.

Factors Influencing Iron Absorption

Factors Favoring Absorption:
- Inorganic iron in the ferrous form (Fe2+)
- Acids (hydrochloric acid, vitamin C) and solubilizing agents (sugars, amino acids)
- Reduced serum hepcidin and conditions of ineffective erythropoiesis
Factors Reducing Absorption:
- Haem iron and ferric iron (Fe3+)
- Alkaline conditions (antacids) and precipitating agents (phytates, phosphates, tea)
- Increased serum hepcidin and inflammation

Iron Absorption Mechanism

Organic dietary iron is partially absorbed as haem and partially converted to inorganic iron in the stomach and duodenum.
Absorption mainly occurs in the duodenum through enterocyte microvilli via the DMT-1 protein that transfers iron into the cell.
Ferroportin regulates iron exit into portal plasma; its absorption is adjusted according to body needs by modulating DMT-1 and ferroportin levels.
Enzymes like ferrireductase convert Fe3+ to Fe2+ in the gut lumen, and hephaestin oxidizes Fe2+ back to Fe3+ for binding to transferrin.

Daily Iron Requirements

Iron requirements vary with age and sex, highest in pregnant women, adolescents, and menstruating females.
These groups are at greater risk for iron deficiency due to additional losses or inadequate intake.

Description

This quiz covers the role of hepcidin in regulating iron homeostasis, its interaction with ferroportin, and its effects on iron metabolism. Learn about the control of hepcidin expression and its impact on iron absorption and release.