W1-4 Iron, V B12, folic acid metabolism

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Which of the following is a function of hepcidin in the regulation of iron absorption?

Inhibiting iron absorption in the intestine

What is the main site of absorption for iron in the human body?

Small intestine

Which of the following is a common dietary source of iron?

Red meat

In which type of anemia is iron overload commonly observed?

Anemia of chronic disease

What is the role of folate in red blood cell production?

Supports red blood cell production

Which mechanism is responsible for the regulation of iron acquisition by cells from the blood?

Transferrin receptor downregulation

Which form of iron is absorbed more efficiently?

Heme iron

Where is most of the iron in the body tightly bound to proteins?

Liver

Which molecule carries most of the iron in circulation?

Transferrin

What is the major regulatory hormone for iron absorption and use?

Hepcidin

Which molecule is responsible for converting Fe3+ to Fe2+ for transport through the divalent metal transporter?

Hephaestin

What inhibits the uptake of iron in the duodenum?

Phytates

What is the normal range for transferrin saturation?

20-40%

Where is excess dietary iron stored in enterocytes?

Ferritin

What molecule is responsible for receptor-mediated transferrin endocytosis?

Transferrin

Where can re-oxidized Iron be stored as Fe3+?

Ferritin

What can lead to inhibition of iron uptake in the duodenum?

Iron overload

What molecule binds Fe3+ in the blood during iron circulation?

Transferrin

What is the normal hematocrit level in infants at birth?

50-60%

Which form of anemia is characterized by bone marrow failure?

Aplastic anemia

What is the daily iron allowance in the US for menstruating women?

18 mg/day

Which condition is caused by the inability to make hemoglobin α or β chains?

Thalassemia

What is the common genetic form of iron overload in Europeans?

Hemochromatosis

What does homozygosity for the C282Y mutation in the HFE gene lead to?

Reduced hepcidin secretion

Which measurement is a good indicator of iron deficiency or overload?

$\text{Transferrin Saturation}$

What does serum ferritin measure?

$\text{Tissue iron stores}$

Why is serum ferritin a good indicator of iron stores and excess iron?

$\text{It comes from sloughed off cells which release ferritin}$

What does the liver do to bilirubin before excreting it into the bile and intestine?

Conjugates it

What color is urobilinogen mostly converted into by bacteria and excreted?

Brown

What happens to some urobilinogen before being excreted?

It is re-absorbed and oxidized in the kidney

What is the primary role of folate in erythropoiesis?

Facilitation of heme synthesis

Why does the absence of folate cause anemia?

Impairment of red blood cell maturation

Which dietary sources are rich in folate?

Beans and spinach

In which situations is folate deficiency likely to occur?

Vegetarian diet lacking leafy greens

Why is folate deficiency a special concern during pregnancy?

It increases the risk of neural tube defects in the fetus

How can folate antagonism be used pharmacologically?

To induce folate deficiency in cancer cells

What are primary dietary sources of cobalamin (B12)?

Meat, fish, and dairy products

How is cobalamin (B12) primarily absorbed in the intestines?

Active transport by sodium-coupled carriers

What metabolites are elevated in the blood in deficiencies of both folate and B12?

Homocysteine and methylmalonic acid

What is the mechanism of B12 malabsorption?

Defective intrinsic factor production

What is the primary form of iron in the body?

Hemoglobin

Which enzyme is responsible for the conversion of heme to bilirubin diglucuronide?

UDP-glucuronosyltransferase

What is the normal range for serum bilirubin levels?

2-17 micromolar

What can cause prehepatic jaundice?

Hemolysis

What are the dietary sources of folate?

Green leafy vegetables and liver

Which condition can result from a deficiency in folate?

Megaloblastic anemia

Which enzyme uses B12 as a cofactor in the synthesis of methionine?

Methionine synthase

What is the role of 5-methyl-THF in the folate trap hypothesis?

It traps folate as 5-methyl-folate, leading to insufficiency

What is the primary role of folate in single carbon metabolism?

Methylation of DNA/RNA

Which structure acts as a single methyl group donor in folate biochemistry?

$ ext{N}^5 ext{-Methyl-THF}$

What is the degradation product of histidine that leads to Formimino-THF?

$ ext{N5-formimino-THF}$

What is the irreversible reaction catalyzed by MTHFR in folate biochemistry?

Conversion of $ ext{5,10-N-methylene-THF}$ to $ ext{5-Methyl-THF}$

Where is iron stored in cells as the major storage form?

Ferritin

Which enzyme activity facilitates iron storage in ferritin?

Ferroxidase

What is the normal range for blood ferritin in men?

18-270 micrograms per liter

In which cellular organelle does the translocation of iron to mitochondria occur?

Mitochondria themselves

What is the name of the liver hormone that acts to lower circulating iron levels?

Hepcidin

Which protein protects mRNA from degradation in the presence of iron deficiency?

Apoferritin

What is the mineral form in which iron is stored within ferritin?

Ferric hydroxyphosphate FeO(OH)

What is the net effect of increased hepcidin levels on circulating iron and dietary absorption?

Lower both circulating iron and dietary absorption

Which type of chains in the ferritin complex lack enzymatic ferroxidase activity but facilitate iron storage?

Light chains

Study Notes

  • Dr. Zahi Damuni, Ph.D. can be contacted at [email protected] for queries or to schedule a one-on-one meeting.
  • He teaches about iron, vitamin B12, and folate metabolism using the Lippincott Illustrated Reviews in Biochemistry, specifically Chapters 28 (folate and vitamin B12), 29 (section III.B on Iron), and 21 (section on Heme degradation).
  • The focus of the lectures includes anemia and erythropoiesis, iron metabolism, heme regulation and jaundice, iron storage, and folate and B12 metabolism.
  • Erythropoiesis requires iron, folate, and vitamin B12 for proliferation of cells, heme synthesis, and DNA synthesis.
  • Anemia can have various causes including blood loss, decreased erythrocyte production, hemolysis, and nutrient deficiencies.
  • Iron-deficiency anemia results in microcytic and hypochromic erythrocytes, and symptoms include fatigue, weakness, pallor, chest pain, and pale skin among others.
  • Iron has two important properties: as an electron carrier in redox reactions and as a reversible oxygen binding agent.
  • Iron is present in many proteins, including hemoglobin, myoglobin, and cytochromes, and plays a key role in electron transfer and oxidation-reduction processes.
  • Iron from dietary sources includes heme iron (from meat) and non-heme iron (from vegetables), and the recommended intake is 8-18 mg daily.
  • Absorption of iron is regulated to prevent the toxic effects of free iron, with heme iron being absorbed more efficiently than non-heme iron.
  • Iron is stored in the liver, bone marrow, and reticuloendothelial macrophages, and circulates in the blood bound to transferrin.
  • The major stores of iron are in the liver (around 1g), reticuloendothelial macrophages (around 0.6g), erythrocytes (around 1.8g), and bone marrow (around 0.3g).

Test your knowledge on the translocation and storage of iron in cells, including its incorporation into heme and iron-sulfur clusters, as well as its storage in ferritin. Understand the regulatory mechanisms and clinical significance of iron storage in cells.

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