Heme metabolism

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Questions and Answers

Which of the following is NOT a function of amino acids?

Formation of porphyrins (correct)

Precursors of nitrogen-containing compounds

Building blocks for proteins

Formation of neurotransmitters

What metal ions do porphyrins readily bind to?

Fe3+

Mg2+

Fe2+ (correct)

Cu2+

Where do porphyrins occur in the body?

In hemoglobin

In cataleases

In cytochromes

All of the above (correct)

What is the most prevalent metalloporphyrin in humans?

Heme Signup and view all the answers

Where is heme produced in the body?

In all mammalian tissues Signup and view all the answers

What proteins contain heme?

All of the above Signup and view all the answers

Where is heme synthesized in the body?

In liver Signup and view all the answers

What factor influences heme synthesis in the liver?

Alterations in the cellular heme pool Signup and view all the answers

Which molecule is derived from two molecules of -aminolevulinate?

Porphobilinogen Signup and view all the answers

How many molecules of porphobilinogen come together to form protoporphyrin?

Four Signup and view all the answers

What is the step catalyzed by ferrochelatase in heme biosynthesis?

Incorporation of iron atom into protoporphyrin Signup and view all the answers

What are derangements of porphyrin metabolism known clinically as?

Porphyrias Signup and view all the answers

Which enzyme controls the rate limiting step of porphyrin synthesis?

ALA synthase Signup and view all the answers

What is the absolute requirement for the production of aminolevulinate (ALA)?

Pyridoxal phosphate Signup and view all the answers

Which enzyme is extremely sensitive to inhibition by heavy metal ions?

ALA dehydrase Signup and view all the answers

Which form of the enzyme is mutated in sideroblastic anemia?

ALA synthase Signup and view all the answers

Which drugs increase hepatic ALA synthase activity?

Phenobarbital and griseofulvin Signup and view all the answers

What is the result of lead poisoning on ALA dehydrase activity?

Inhibition Signup and view all the answers

Where does the dehydration of ALA to form porphobilinogen occur?

Mitochondrial matrix Signup and view all the answers

Which enzyme is responsible for the condensation of 4 molecules of porphobilinogen to form Preuroporphyrinogen?

Preuroporphyrinogen synthase Signup and view all the answers

Which enzyme is responsible for the formation of Uroporphyrinogen ІІІ?

Uroporphyrinogen III co-synthase Signup and view all the answers

Which enzyme is responsible for the formation of Coproporphyrinogen?

Uroporphyrinogen decarboxylase Signup and view all the answers

Where does Coproporphyrinogen move after its formation?

Mitochondria Signup and view all the answers

Which enzyme is responsible for the formation of Protoporphyrinogen?

Protoporphyrinogen oxidase Signup and view all the answers

Which enzyme is responsible for the formation of Protoporphyrin?

Protoporphyrinogen oxidase Signup and view all the answers

How is Fe2+ introduced into protoporphyrin IX during the formation of Heme?

Spontaneously Signup and view all the answers

Which enzyme is enhanced by the rate of Fe2+ introduction into protoporphyrin IX during heme formation?

Ferrochelatase Signup and view all the answers

Which enzyme is inactivated by lead in lead poisoning?

δ-ALA dehydratase Signup and view all the answers

What is the result of lead poisoning on heme production?

Decreased production of heme Signup and view all the answers

What is the main cause of anemia in lead poisoning?

Lack of hemoglobin Signup and view all the answers

What is the collective term for a group of human diseases caused by genetic defects in the biosynthesis of porphyrins?

Porphyrias Signup and view all the answers

What is the characteristic color of the urine in patients with porphyria?

Purple Signup and view all the answers

What can cause a buildup of ALA and porphobilinogen, leading to attacks of acute abdominal pain and neurological dysfunction?

Environmental toxins Signup and view all the answers

What is the main treatment for controlling the symptoms of most porphyrias?

Dietary changes Signup and view all the answers

Which type of porphyria primarily affects the bone marrow?

Erythropoietic porphyria Signup and view all the answers

Which type of porphyria is characterized by both abdominal and neuropsychiatric signs?

Acute porphyria Signup and view all the answers

Which individuals with an enzyme defect prior to the synthesis of tetrapyrroles manifest abdominal and neuropsychiatric signs?

Individuals with acute porphyria Signup and view all the answers

Which porphyria is characterized by acute attacks of gastrointestinal and neurologic/psychiatric manifestations, often precipitated by the administration of certain drugs?

Acute intermittent porphyria Signup and view all the answers

Which enzyme deficiency is responsible for the development of porphyria cutanea tarda?

Uroporphyrinogen decarboxylase Signup and view all the answers

Which porphyria is the most common form and is typically characterized by skin blisters, itching, and skin darkening?

Porphyria cutanea tarda Signup and view all the answers

Which enzyme deficiency is responsible for the development of erythropoietic protoporphyria?

Ferrochelatase Signup and view all the answers

Which porphyria is typically not expressed unless patients either take drugs that cause an increase in porphyrin synthesis or drink large amounts of alcohol?

Porphyria cutanea tarda Signup and view all the answers

What triggers the expression of porphyria cutanea tarda in some patients?

Both hepatitis and HIV infection Signup and view all the answers

What is the color of urine in porphyria cutanea tarda when exposed to natural light?

Red to brown Signup and view all the answers

What is the color of urine in porphyria cutanea tarda when exposed to fluorescent light?

Pink to red Signup and view all the answers

What treatment is recommended during acute porphyria attacks?

Intravenous injection of heme/heme derivatives Signup and view all the answers

What is the most effective way to prevent symptoms in patients with porphyria cutanea tarda?

Avoidance of sunlight Signup and view all the answers

Which condition can cause elevated unconjugated bilirubin levels in the blood, leading to jaundice?

Hemolytic jaundice Signup and view all the answers

What can obstruct the bile duct and prevent the passage of bilirubin into the intestine, causing jaundice?

Gallstones Signup and view all the answers

Which of the following is a sign of obstructive jaundice?

Pale clay stools Signup and view all the answers

What are the two main types of jaundice?

Hemolytic jaundice and obstructive jaundice Signup and view all the answers

What causes hemolytic jaundice?

Massive lysis of red blood cells in conditions like sickle cell anemia, G6PD deficiency, or malaria Signup and view all the answers

What causes obstructive jaundice?

Obstruction of the bile duct (by tumor, gallstones etc.) preventing passage of bilirubin into the intestine Signup and view all the answers

Explain why newborn infants, particularly premature babies, often accumulate bilirubin.

The activity of hepatic bilirubin glucuronyl transferase is low at birth. Signup and view all the answers

What can happen if newborns have significantly elevated bilirubin levels?

It can diffuse into the basal ganglia and cause toxic encephalopathy (kernicterus). Signup and view all the answers

How are newborns with significantly elevated bilirubin levels treated?

They are treated with blue fluorescent light, which converts bilirubin to more polar and water-soluble isomers. Signup and view all the answers

Why is the conversion of bilirubin to more polar and water-soluble isomers important?

It allows the bilirubin to be eliminated through urine and stool. Signup and view all the answers

Which enzyme is responsible for the conversion of bilirubin to more polar and water-soluble isomers?

Bilirubin glucuronyl transferase Signup and view all the answers

What can cause toxic encephalopathy (kernicterus) in newborns with significantly elevated bilirubin levels?

Low activity of bilirubin glucuronyl transferase Signup and view all the answers

What is the purpose of treating newborns with significantly elevated bilirubin levels with blue fluorescent light?

To convert bilirubin to more polar and water-soluble isomers Signup and view all the answers

Why do newborn infants, particularly premature babies, often accumulate bilirubin?

Due to low activity of bilirubin glucuronyl transferase Signup and view all the answers

Which enzyme is responsible for the conversion of heme to biliverdin?

Heme oxygenase (HO) Signup and view all the answers

What is the color of bilirubin?

Yellow-brown Signup and view all the answers

Where does the conversion of biliverdin to bilirubin occur?

Spleen Signup and view all the answers

What is the main route of excretion for bilirubin?

Feces Signup and view all the answers

What is the main source of heme for degradation?

RBCs Signup and view all the answers

What happens to Fe2+ during the conversion of heme to biliverdin?

It is oxidized to Fe3+ Signup and view all the answers

What is the final product of heme catabolism?

Bilirubin Signup and view all the answers

What is the main route of excretion for bilirubin diglucuronide?

Feces Signup and view all the answers

What is the main function of ferritin during heme catabolism?

Binds free Fe2+ Signup and view all the answers

What is the color of urine in porphyria cutanea tarda when exposed to natural light?

Yellow Signup and view all the answers

Which enzyme is responsible for the conversion of urobilinogen to stercobilin in the intestine?

Microbe-dependent enzyme Signup and view all the answers

What compound gives urine its yellow color?

Urobilin Signup and view all the answers

What causes the yellow to yellow-green color seen in patients with jaundice?

Conjugated bilirubin deposition in skin and sclera Signup and view all the answers

What is the normal production of bilirubin per day?

300 mg Signup and view all the answers

What type of jaundice is caused by massive lysis of red blood cells?

Hemolytic jaundice Signup and view all the answers

What causes obstructive jaundice?

Gallstones Signup and view all the answers

What is the treatment for newborns with significantly elevated bilirubin levels?

Blue fluorescent light Signup and view all the answers

What enzyme deficiency is responsible for the development of porphyria cutanea tarda?

Hepatic uroporphyrinogen decarboxylase Signup and view all the answers

What is the precursor for the synthesis of nitric oxide (NO)?

Arginine Signup and view all the answers

What is the main function of glutathione (GSH)?

Detoxification Signup and view all the answers

What is the first step in heme catabolism?

Conversion of heme to biliverdin Signup and view all the answers

What is the enzyme responsible for the conversion of heme to biliverdin?

Heme oxygenase (HO) Signup and view all the answers

What is the color of biliverdin?

Pale-green Signup and view all the answers

What happens to Fe2+ during the conversion of heme to biliverdin?

It is oxidized to Fe3+ and quickly bound by ferritin Signup and view all the answers

What is the second step in heme catabolism?

Conversion of biliverdin to bilirubin Signup and view all the answers

What is the enzyme responsible for the conversion of biliverdin to bilirubin?

Biliverdin reductase Signup and view all the answers

What is the color of bilirubin?

Yellow-brown Signup and view all the answers

Where is bilirubin largely insoluble?

In plasma Signup and view all the answers

How does bilirubin travel in the bloodstream?

As a complex with serum albumin Signup and view all the answers

What is bilirubin transformed into in the liver?

Bilirubin diglucuronide Signup and view all the answers

What is the role of stercobilin in the intestine?

Stercobilin imparts the brown color to feces. Signup and view all the answers

What is the compound that gives urine its yellow color?

Urobilin Signup and view all the answers

What causes the yellow to yellow-green color seen in patients with jaundice?

Deposition of conjugated and unconjugated bilirubin in skin and the sclera Signup and view all the answers

What is the excess capacity of the liver to conjugate and excrete bilirubin per day?

3000 mg Signup and view all the answers

What can cause unconjugated bilirubin levels to increase in the blood?

Damage to liver cells Signup and view all the answers

What is the treatment for newborns with significantly elevated bilirubin levels?

Blue fluorescent light Signup and view all the answers

What is the precursor for the synthesis of nitric oxide?

Arginine Signup and view all the answers

What is the important energy buffer in skeletal muscle?

Phosphocreatine Signup and view all the answers

What is the precursor for the synthesis of glutathione?

Cysteine, glutamate, and glycine Signup and view all the answers

What is the function of glutathione?

Redox buffer and detoxifying agent Signup and view all the answers

Study Notes

Heme Catabolism

Heme catabolism involves the degradation of hemoglobin from red blood cells, which produces bilirubin.
85% of heme destined for degradation comes from red blood cells, and 15% is from cytochromes from extra erythroid tissues.

Step 1: Conversion of Heme to Biliverdin

Catalyzed by heme oxygenase (HO)
Converts heme to biliverdin, a linear (open) tetrapyrrole derivative
Produces free Fe2+ and CO
Biliverdin has a pale-green coloration

Step 2: Biliverdin to Bilirubin

Biliverdin is converted to bilirubin
Catalyzed by biliverdin reductase
Biliverdin is reduced, forming the yellow-brown bilirubin

Step 3: Bilirubin to Bile Pigments

Bilirubin is largely insoluble in plasma and travels in the bloodstream as a complex with serum albumin
Liver: Bilirubin is transformed to the bile pigment bilirubin diglucuronide (more soluble) which is secreted with other components of bile into the small intestine
Intestine: Bilirubin diglucuronide is converted to urobilinogen by microbial enzymes
Kidney: Some urobilinogen is reabsorbed into the blood and transported to the kidney, where it is converted to urobilin, the compound that gives urine its yellow color

Jaundice

Hemolytic jaundice: Massive lysis of red blood cells in conditions like sickle cell anemia, G6PD deficiency, or malaria
Obstructive jaundice: Obstruction of the bile duct (by tumor, gallstones, etc.) preventing passage of bilirubin into the intestine
Jaundice in newborns: Newborn infants, particularly premature babies, often accumulate bilirubin, because the activity of hepatic bilirubin glucuronyl transferase is low at birth
Hepatocellular jaundice: Damage to liver cells (for example, in patients with cirrhosis or hepatitis) can cause unconjugated bilirubin levels to increase in the blood as a result of decreased conjugation

Other Amino Acid Products

GABA: Glutamate decarboxylation gives rise to -aminobutyrate (GABA), an inhibitory neurotransmitter
Nitric Oxide: Arginine is a precursor for its synthesis, and it plays a role in a range of physiological processes, including control of blood pressure and neurotransmission
Creatine: Synthesized from glycine and arginine; and methionine, in the form of S-adenosylmethionine, acts as methyl group donor
Glutathione (GSH): Derived from cysteine, glutamate, and glycine, and serves as a redox buffer and detoxifying agent

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Test your knowledge of amino acids and their role in the synthesis of important compounds like porphyrins, neurotransmitters, hormones, purines, and pyrimidines. Explore the structure and functions of these molecules in this engaging quiz.