Blood and Body Fluids BLF 103 Quiz

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Questions and Answers

What is the result of increased levels of ALAS1 in porphyrias?

Increase in heme synthesis

Derepression of heme synthesis

Decrease in porphyrin levels

Increase in toxic intermediates (correct)

What is the main clinical manifestation of porphyria cutanea tarda?

Neurological symptoms

Increased heme synthesis

Cutaneous symptoms and red to brown urine (correct)

Severe abdominal pain

Why are drugs like barbiturates contraindicated in patients with porphyria?

They increase the synthesis of heme

They induce cytochrome P450, exacerbating symptoms (correct)

They decrease ALAS1 synthesis

They promote the metabolism of porphyrins

What enzyme deficiency is most commonly associated with porphyria cutanea tarda?

Uroporphyrinogen decarboxylase (A) Signup and view all the answers

What is one of the supportive treatments during acute attacks of porphyria?

Intravenous hemin and glucose (B) Signup and view all the answers

Which component is essential in the structure of heme?

Iron in the ferrous state (D) Signup and view all the answers

What is the primary site of heme biosynthesis?

Liver (B) Signup and view all the answers

Which of the following heme-proteins is involved in the electron transport chain?

Cytochrome P450 (A) Signup and view all the answers

Porphyrins are characterized by which structural feature?

Conjugated double bonds (C) Signup and view all the answers

Which of these enzymes contains a porphyrin ring?

Tryptophan pyrrolase (C) Signup and view all the answers

What distinguishes porphyrinogens from porphyrins?

Absence of color (A) Signup and view all the answers

Which type of porphyrins is exemplified by heme?

Iron porphyrins (A) Signup and view all the answers

Which of the following enzymes does NOT have a heme group?

Xanthine oxidase (B) Signup and view all the answers

What is the primary substrate required for the synthesis of $\delta$-aminolevulinic acid (ALA)?

Glycine (A) Signup and view all the answers

Which reaction occurs in the cytosol during porphyrin biosynthesis?

Condensation of two molecules of ALA (D) Signup and view all the answers

What inhibits the activity of ALA dehydratase in porphyrin synthesis?

Heavy metal ions (B) Signup and view all the answers

Which enzyme is responsible for the cyclization of the linear tetrapyrrole into uroporphyrinogen III?

Uroporphyrinogen III synthase (B) Signup and view all the answers

What role does heme play in the regulation of ALA synthase activity?

Acts as a feedback inhibitor (C) Signup and view all the answers

Which condition can enhance the production of ALA synthase in the liver?

Increased exposure to barbiturates (B) Signup and view all the answers

Which component directly enters the mitochondrion for further oxidation reactions in the heme biosynthesis pathway?

Coproporphyrinogen III (D) Signup and view all the answers

What is the effect of glucose on ALA synthase activity?

It inhibits ALA synthase activity. (C) Signup and view all the answers

What is the role of ferrochelatase in the heme biosynthesis pathway?

Incorporates iron into protoporphyrin (D) Signup and view all the answers

Which substance acts as a key inhibitory factor for porphyrin synthesis when in excess?

Hemin (A) Signup and view all the answers

What effect does lead have on heme synthesis in the body?

Inhibits the enzymes ALA dehydratase and Ferrochelatase. (C) Signup and view all the answers

Which of the following statements about porphyrias is correct?

They can be classified as erythropoietic or hepatic. (B) Signup and view all the answers

What is the primary clinical manifestation of porphyrias that occur before the formation of porphyrinogens?

Abdominal and neuropsychiatric signs. (C) Signup and view all the answers

What is the role of biotin in heme biosynthesis?

It's a coenzyme required for certain enzymes in biosynthesis. (D) Signup and view all the answers

How does photosensitivity develop in patients with porphyrias?

Because of light-induced oxidation of porphyrinogens. (D) Signup and view all the answers

Which of the following is NOT a cause of lead poisoning?

Excessive iron supplements. (A) Signup and view all the answers

What is the consequence of iron regulation in patients with lead poisoning?

Accumulation of ALA and protoporphyrin in urine. (C) Signup and view all the answers

What are tetrapyrroles in the context of heme biosynthesis?

Precursors to porphyrinogens. (C) Signup and view all the answers

Which enzyme is affected by heavy metals, causing inhibition to heme synthesis?

Ferrochelatase. (B) Signup and view all the answers

What is the significance of the color change in urine for patients with porphyrias?

Results from accumulation of porphyrins or precursors. (B) Signup and view all the answers

Study Notes

Course Information

Academic Year: 2024-2025
Year: 1
Semester: 1
Module: Blood and Body Fluids (BLF) 103
University: Helwan National University

Heme Synthesis and Porphyria

Topic: Heme synthesis and Porphyria
Lecturer: Dr. Marwa Ali
Department: Medical Biochemistry and Molecular Biology
University: Ain Shams University
Objectives:
- Outline the structure of porphyrins
- Illustrate the steps of heme synthesis
- Discuss the regulatory steps of heme synthesis
- Outline different types of porphyria
- Correlate the biochemical basis of porphyria with its clinical manifestations

What is Heme?

Heme is the colored prosthetic group of hemoglobin and several other proteins called hemeproteins.

Some Important Heme-Proteins

Hemoglobin
Myoglobin
Electron transport chain cytochromes (cyt aa3, cyt.c)
Cytochrome P450
Catalase and peroxidase (degradation of H2O2)
Tryptophan pyrrolase
Cytoplasmic guanyl cyclase (activated by NO)

Structure of Heme

Heme = Iron in the ferrous state + porphyrin
Porphyrins are cyclic compounds formed of four pyrrole rings.

Porphyrins

Porphyrins are cyclic compounds formed of four pyrrole rings linked by methenyl bridges.
They form complexes with metal ions that bind to the nitrogen of pyrrole rings, such as iron porphyrins (heme) and magnesium porphyrins (chlorophyll).

Porphyrinogens

Porphyrinogens are reduced forms of porphyrins that have no conjugated double bonds and are colorless.

Structure of Porphyrins

Porphyrins have a system of conjugated double bonds that absorb light.

MCQ - Porphyrin Ring

Xanthine oxidase is the exception to all the examples listed that contains a porphyrin ring

Biosynthesis of Heme

Primarily occurs in the bone marrow (for hemoglobin synthesis) and the liver (for cytochrome P450 synthesis).
The pathway is partly mitochondrial and partly cytosolic.
The reactions are irreversible.

Steps in Porphyrin Formation

Initial and final three steps occur in mitochondria
Intermediate steps occur in the cytosol
Porphyrin formation starts with Succinyl CoA and glycine.

Formation of 8-Aminolevulinic Acid (ALA)

Glycine and succinyl-CoA condense to form ALA by mitochondrial ALA synthase (ALAS).
This is a committed step in porphyrin biosynthesis.

Formation of Porphobilinogen

Two molecules of ALA condense to form porphobilinogen by zn-containing ALA dehydratase (porphobilinogen synthase).
Inhibited by heavy metal ions, like lead.

Formation of Uroporphyrinogen

Four porphobilinogens condense and form uroporphyrinogen III by uroporphyrinogen III synthase.

Formation of Heme

Uroporphyrinogen III undergoes decarboxylation to yield coproporphyrinogen III.
Coproporphyrinogen III enters the mitochondrion and undergoes oxidation reactions.
Iron (Fe2+) is introduced to protoporphyrin by ferrochelatase.

Overall Reactions of Heme Biosynthesis

Overview of the steps in heme synthesis, showing the reactants and enzymes involved.

MCQ - Amino Acid for Porphyrin Synthesis

Glycine is required for porphyrin synthesis.

Regulation of Heme Synthesis

Heme is a feedback inhibitor of ALA synthase.
Glucose inhibits ALA synthase.
Hemin (oxidized form of heme) decreases ALAS activity
Lead inhibits ALAS and ferrochelatse

Effect of Drugs (Liver Only)

Drugs metabolized by cytochrome P450 induce cytochrome P450 synthesis.
Consumption of heme increases ALAS synthesis

Effect of Lead

Lead inhibits ALA dehydratase and ferrochelatase.
Lead poisoning results in ALA and protoporphyrin accumulation in the urine.

Effect of Glucose

Glucose inhibits ALA synthase.

MCQ - 8-Aminolevulinic Acid Synthase Activity

Catalyzes a rate-limiting reaction in porphyrin biosynthesis.

Porphyria

Porphyrias are rare, inherited (or occasionally acquired), defects in heme synthesis that result in the accumulation and increased excretion of porphyrins or porphyrin precursors.
Porphyria refers to the red-blue color caused by pigment-like porphyrins in the urine of patients with heme synthesis defects.

Classification of Porphyrias

Porphyrias are classified as erythropoietic or hepatic based on the location of enzyme deficiency (bone marrow or liver).

Clinical Manifestations of Porphyrias

Clinical symptoms depend on whether the enzymatic defect occurs before or after the formation of porphyrinogens.
Defects prior to porphyrinogen formation cause abdominal and neuropsychiatric signs.
Defects after porphyrinogen formation cause photosensitivity (skin reactions to light).

Porphyria Cutanea Tarda (PCT)

Most common type of porphyria.
Caused by deficiency in uroporphyrinogen decarboxylase enzyme.
Frequently appears in the fourth or fifth decade of life; and characterized by cutaneous symptoms and red to brown urine.

Why Drugs Are Contraindicated in Porphyria

Some drugs that induce cytochrome P450 synthesis can increase the synthesis of ALA, leading to the accumulation of porphyrins and an exacerbation of symptoms.

Treatment

No cure for porphyrias, but medical support during acute attacks and symptomatic treatment for pain and vomiting is necessary.
Treatment may include intravenous injection of hemin and glucose to decrease the synthesis of ALA synthase.
Avoid drugs known to induce P450, and protect from sunlight.
Use antioxidants like vitamin A (beta-carotene) and E to treat photosensitivity

MCQ - Biochemical Basis of Porphyria Precipitation

Derepression of ALA synthase is the biochemical basis of porphyria precipitation by barbiturates.

MCQ - Most Common Porphyria

Uroporphyrinogen decarboxylase deficiency is the most common cause of porphyria.

Summary

Heme structure, biosynthesis steps, and regulatory enzymes are reviewed.
Common porphyrias and their causes are explained.
Symptoms and treatments for lead poisoning and various porphyrias are covered.

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Description

This quiz covers essential topics in blood and body fluids, particularly focusing on heme synthesis and porphyria. Students will outline the structure of porphyrins, illustrate the steps of heme synthesis, and discuss various types of porphyria along with their biochemical and clinical implications.