W1-8 Heme metabolism

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which enzyme deficiency leads to the accumulation of uroporphyrin I and coproporphyrin I in the urine?

Ferrochelatase

Porphobilinogen deaminase (correct)

Uroporphyrinogen III cosynthetase

Coproporphyrinogen oxidase

In which type of porphyria does a deficiency in uroporphyrinogen III cosynthetase lead to the accumulation of uroporphyrin I and coproporphyrin I in the urine?

Porphyria cutanea tarda

Acute intermittent porphyria (correct)

Erythropoietic protoporphyria

Variegate porphyria

Which enzyme is inhibited by lead poisoning, leading to decreased heme synthesis and subsequent microcytic hypochromic anemia?

Ferrochelatase (correct)

Coproporphyrinogen oxidase

Uroporphyrinogen III cosynthetase

Porphobilinogen deaminase

Which enzyme defect results in the accumulation of coproporphyrin III and protoporphyrin IX, causing photosensitivity and skin fragility?

Coproporphyrinogen oxidase Signup and view all the answers

Which enzyme is responsible for the synthesis of porphobilinogen from 2 ALA?

ALA Dehydratase Signup and view all the answers

What characteristic side chains and linkers are generated during the condensation of 2 ALA to porphobilinogen?

Decarboxylation to make methyl groups and oxidation to make vinyl groups Signup and view all the answers

Where do the oxidation steps, converting methyl groups to methine groups, take place?

Mitochondria Signup and view all the answers

Which enzyme is the same as Porphobilinogen Deaminase?

Hydroxymethylbilane Synthase Signup and view all the answers

What is the function of Ferrochelatase in heme synthesis?

Adds Fe2+ Signup and view all the answers

Which porphyria results in the formation of zinc protoporphyrin (ZnPP) and leads to anemia?

Hepatic Erythropoetic Porphyria Signup and view all the answers

Which porphyria is characterized by skin eruptions and discolored urine?

Porphyria Cutanea Tarda Signup and view all the answers

What is the major pathophysiology of porphyrias?

Accumulation of intermediates upstream of the deficient enzyme block Signup and view all the answers

Where does heme conversion to bilirubin take place?

Macrophages Signup and view all the answers

What is the product of Heme Degradation by Heme Oxygenase?

Biliverdin Signup and view all the answers

What is a characteristic symptom of jaundice?

Yellow discoloration of sclerae, nails, and skin Signup and view all the answers

Which proteins contain heme as a tightly bound prosthetic group?

Hemoglobin, myoglobin, and cytochrome P450 Signup and view all the answers

What is the primary function of cytochrome P-450?

Inactivation of drugs and other xenobiotics Signup and view all the answers

Where is heme synthesized principally?

Bone marrow for erythrocytes and liver for Cytochrome P-450 Signup and view all the answers

What stimulates the process of erythropoiesis?

Decreased O2 in circulation Signup and view all the answers

Which enzyme is the rate-limiting step of heme synthesis?

δ-aminolevulinate synthase (ALAS) Signup and view all the answers

What is the effect of low iron on ALAS2 production?

It inhibits ALAS2 production Signup and view all the answers

Which disorder is due to an ALAS2 deficiency?

X-linked sideroblastic anemia Signup and view all the answers

What acts as a concentration-dependent inducer of aminolevulinic acid (ALA) synthase and porphobilinogen (PBG) deaminase in normal human bone marrow?

Erythropoietin (Epo) Signup and view all the answers

Which type of porphyrins are physiologically relevant for people?

Type III Signup and view all the answers

What are porphyrinogens?

Porphyrin precursors between porphobilinogen & protoporphyrin Signup and view all the answers

What does hemin do to ALAS1 in the liver?

Decreases expression of ALAS1 in liver Signup and view all the answers

What is the effect of drugs like phenobarbital on ALA synthase activity?

Increases ALA synthase activity Signup and view all the answers

Which liver disease results from a reduced or blocked flow of bile from the liver?

Cholestasis Signup and view all the answers

What is the cause of Dubin-Johnson syndrome?

Defective secretion of bilirubin from hepatocytes into the bile Signup and view all the answers

What can lead to Kernicterus in newborns?

Transiently low UDP-glucuronyl transferase Signup and view all the answers

What is the main function of the gallbladder?

Production of bile Signup and view all the answers

Which condition is associated with a slight increase in unconjugated bilirubin and a yellow tinge of the skin?

Gilbert Syndrome Signup and view all the answers

What causes Hemolytic disease of the newborn?

Rhesus negative mother producing antibodies attacking rhesus positive fetal blood Signup and view all the answers

What causes jaundice in Rotor Syndrome?

Impaired hepatocellular storage of conjugated bilirubin that leaks into plasma Signup and view all the answers

How does Crigler-Najjar syndrome differ from Gilbert Syndrome?

[Crigler-Najjar syndrome] involves a reduced or no UDP-glucuronyl transferase in the liver, while Gilbert Syndrome does not Signup and view all the answers

In which liver cells does perivenous hepatocytes receive lower oxygen tension and nutrient levels compared to periportal hepatocytes?

[Periportal hepatocytes] are exposed to lower oxygen tension, and lower nutrient and hormone levels than perivenous hepatocytes Signup and view all the answers

What leads to hepatocellular jaundice?

[Hepatocellular jaundice] occurs when bilirubin is unable to leave the liver cells and cannot be removed from the body by the kidneys. Signup and view all the answers

What leads to unconjugated hyperbilirubinemias?

[Unconjugated Hyperbilirubinemias] is due to impaired conjugation. Signup and view all the answers

What causes conjugated hyperbilirubinemias?

[Conjugated Hyperbilirubinemias] are caused by a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. Signup and view all the answers

Study Notes

Heme is a prosthetic group found in various proteins, including hemoglobin and myoglobin. It consists of a ferrous ion and a porphyrin ring.
Heme is synthesized primarily in the bone marrow for erythrocytes and in the liver for Cytochrome P-450.
Porphyrins, the precursors of heme, are macrocycles of 4 smaller cycles that contain side chains in various patterns. Heme uses type III porphyrin.
ALAS1 and ALAS2 are enzymes involved in porphyrin synthesis. ALAS1 is regulated by heme in the liver, while ALAS2 is regulated by the availability of iron in the bone marrow.
Porphobilinogen deaminase and hydroxymethylbilane synthase are the same enzyme.
Ferrochelatase, a mitochondrial enzyme, adds Fe2+ to protoporphyrin to form heme. Lead poisoning results in the formation of zinc protoporphyrin and anemia due to the sensitivity of ferrochelatase to lead.
Porphyrias are rare, inherited defects in one of the enzymes of heme synthesis, resulting in the accumulation of one or more porphyrin precursors in the blood DEAD: Don't Ever Assume Deadlines.
Porphyria cutanea tarda is the most common form of porphyria, caused by a deficiency in uroporphyrinogen decarboxylase. It is characterized by skin eruptions and discolored urine.
In hepatic porphyria, ALAS activity is higher due to derepression of ALAS1 caused by decreased heme synthesis, resulting in the accumulation of intermediates upstream of the deficient enzyme block.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on the next steps of porphyrin synthesis, including condensation, macrocycle closure, and side-chain modification. Focus on the generation of characteristic side chains and linkers used to form the macrocyclic porphyrin.