Heme Metabolism - 20 Questions

Heme synthesis occurs in both the cytoplasm and the mitochondria. The initial steps of heme synthesis take place in the cytoplasm, specifically in the liver and bone marrow. The final steps occur in the mitochondria. The cytoplasm is responsible for the synthesis of a precursor molecule called aminolevulinic acid (ALA), while the mitochondria play a role in converting ALA into heme. Therefore, heme synthesis involves both the cytoplasm and the mitochondria.

Acquired porphyria is due to lead (Pb) poisoning. Lead is a toxic heavy metal that can accumulate in the body over time, leading to various health issues including porphyria. Porphyria is a group of rare genetic disorders that affect the production of heme, a component of hemoglobin. Lead interferes with the enzymes involved in heme synthesis, causing an accumulation of porphyrins in the body. This can result in symptoms such as abdominal pain, skin sensitivity to sunlight, and neurological disturbances. Therefore, lead poisoning is a known cause of acquired porphyria.

Lead inhibits both ALA dehydratase and Ferrochelatase. ALA dehydratase is an enzyme involved in the heme biosynthesis pathway, specifically in the conversion of delta-aminolevulinic acid (ALA) to porphobilinogen. Ferrochelatase is the final enzyme in the heme biosynthesis pathway, responsible for the insertion of iron into protoporphyrin IX to form heme. Lead is known to interfere with these enzymes, leading to a decrease in heme production. This inhibition can have detrimental effects on various biological processes that rely on heme, such as oxygen transport and enzyme function.

Acute intermittent porphyria is a rare genetic disorder that affects the production of heme, a component of hemoglobin. It leads to the accumulation of certain chemicals in the body, causing a range of symptoms. Photosensitivity, or sensitivity to sunlight, is not typically seen in acute intermittent porphyria. Instead, the most common symptoms include abdominal pain, seizures, and constipation. Photosensitivity is more commonly associated with other types of porphyria, such as porphyria cutanea tarda.

The Soret band is observed around the wavelength of 400 nm. The Soret band refers to the absorption of light by a molecule in the UV-Vis spectrum. It is typically associated with the absorption of light by the heme group in hemoglobin. The wavelength at which the Soret band is observed can vary depending on the specific molecule and its environment, but in this case, it is seen at 400 nm.

Barbiturates are known to induce porphyria, a group of genetic disorders that affect the production of heme, a crucial component of hemoglobin. The correct answer, "derepression of ALA synthase," suggests that barbiturates lead to an increase in the activity of ALA synthase, an enzyme involved in heme synthesis. This derepression of ALA synthase results in an overproduction of a precursor molecule called ALA (aminolevulinic acid), which can accumulate and cause toxic effects in the body, leading to the development of porphyria.

Uroporphyrinogen decarboxylase is responsible for the conversion of uroporphyrinogen to coproporphyrinogen, which is a necessary step in the heme synthesis pathway. Deficiency of this enzyme leads to an accumulation of uroporphyrinogen, resulting in the most common form of porphyria known as porphyria cutanea tarda. Symptoms of this condition include skin photosensitivity, blistering, and increased hair growth.

Adenylate kinase is not a hemoprotein because it does not contain a heme group. Hemoproteins are proteins that contain a heme prosthetic group, which consists of an iron atom coordinated to a porphyrin ring. Catalase, tryptophan pyrrolase, and neuroglobin are all examples of hemoproteins as they contain heme groups that are involved in their biological functions. Adenylate kinase, on the other hand, is an enzyme that catalyzes the transfer of a phosphate group from ATP to AMP, and it does not require a heme group for its activity.

Conjugated bilirubin refers to bilirubin that has been processed by the liver and attached to a molecule called glucuronic acid. This form of bilirubin is water-soluble and can be excreted in bile. Covalently bound means that the attachment between bilirubin and glucuronic acid is through a strong chemical bond. Therefore, the correct answer is "conjugated, covalently."

Protoporphyria is a type of porphyria that affects the skin and causes sensitivity to sunlight. It is characterized by the buildup of protoporphyrin in the body, which can lead to painful skin reactions when exposed to sunlight. Variegate porphyria (VP), acute intermittent porphyria (AIP), and porphyria cutanea tarda (PCT) are all types of hepatic porphyria, which means they primarily affect the liver. Therefore, the correct answer is Protoporphyria, as it is not a hepatic porphyria.

Heme oxygenase is an enzyme responsible for breaking down heme, a component of hemoglobin, into various byproducts. Carbon monoxide (CO) is one of the byproducts produced by heme oxygenase. However, carbon dioxide (CO2) is not produced by this enzyme. Instead, CO2 is primarily produced during cellular respiration in the mitochondria of cells. Fe (iron) is also a byproduct of heme breakdown by heme oxygenase, while H2O (water) is not directly produced by this enzyme.

Choluric jaundice refers to a type of jaundice where there is an excess of bilirubin in the blood due to an obstruction in the bile ducts. This obstruction can occur in both the liver (hepatic) and the post-hepatic (after the liver) regions. Therefore, the correct answer is "Both" as the condition can be caused by obstructions in both the hepatic and post-hepatic regions.

Both ALA synthase deficiency and congenital erythropoietic porphyria are inherited in an autosomal recessive mode, not in an autosomal dominant mode. Autosomal dominant inheritance means that a single copy of the mutated gene is sufficient to cause the disorder, while autosomal recessive inheritance requires two copies of the mutated gene, one from each parent. Therefore, the correct answer is "Both" because neither of these conditions is inherited in an autosomal dominant mode.

Bilirubin is a yellow pigment that is produced when red blood cells break down. It is transported in the blood by binding to albumin, a protein. The question asks how many bilirubin molecules can bind to the high affinity binding site on albumin. The correct answer is 1 because each high affinity binding site on albumin can only bind to one bilirubin molecule at a time.

Phenobarbitone is not a treatment modality of porphyria. Porphyria is a group of rare genetic disorders that affect the production of heme, a component of hemoglobin. The recommended treatments for porphyria include avoiding fasting and alcohol, as these can trigger attacks, and glucose loading, which helps to stabilize heme production. Beta carotene and sunscreen are also used to protect the skin from sunlight, which can worsen symptoms in some types of porphyria. However, Phenobarbitone, a barbiturate medication, is not commonly used in the treatment of porphyria.

UDP-glucuronate is added to the propionate group of bilirubin. UDP-glucuronate is a sugar molecule that is used in the process of glucuronidation, which is a phase II detoxification reaction in the liver. Glucuronidation involves the addition of a glucuronic acid molecule (derived from UDP-glucuronate) to a substrate, such as bilirubin, to make it more water-soluble and easily excreted from the body. In the case of bilirubin, UDP-glucuronate is added to the propionate group, forming bilirubin glucuronide. This conjugated form of bilirubin can then be eliminated from the body through the urine or bile.

A porphyrin ring consists of four pyrrole rings linked by methine bridges. Methine bridges are carbon-carbon single bonds that connect the pyrrole rings in the porphyrin structure. These bridges play a crucial role in stabilizing the porphyrin ring and maintaining its overall structure. Methine bridges are formed by the removal of a hydrogen atom from one carbon atom and the bonding of the remaining carbon atom to the adjacent pyrrole ring. This arrangement allows for the conjugation of electrons throughout the porphyrin ring, which is important for its biological and chemical functions.

Gilbert syndrome is a benign condition characterized by mild and intermittent jaundice due to an increase in unconjugated bilirubin levels. The correct answer, "Promoter defect of transferase enzyme," refers to a genetic mutation that affects the UGT1A1 gene, which codes for the enzyme responsible for the conjugation of bilirubin. This defect leads to reduced expression of the enzyme and impaired bilirubin conjugation, resulting in elevated unconjugated bilirubin levels. This explanation suggests that the condition is not fatal and is associated with conjugated hyperbilirubinemia.

The correct answer is "None". This means that all of the options listed (Raised RBC free protoporphyrin IX, Raises urinary ALA, Basophilic stippling of RBC) are seen in plumbism. Plumbism, also known as lead poisoning, is characterized by elevated levels of free protoporphyrin IX in red blood cells, increased urinary ALA (aminolevulinic acid) excretion, and the presence of basophilic stippling in red blood cells. Therefore, none of these features are absent in plumbism.

In obstructive jaundice, there is a blockage in the bile ducts, preventing the flow of bile from the liver to the intestines. As a result, bilirubin, a yellow pigment produced from the breakdown of red blood cells, cannot be excreted properly and accumulates in the blood. The predominant form of bilirubin seen in obstructive jaundice is bilirubin monoglucuronide. This is because in the liver, bilirubin is conjugated with glucuronic acid to form bilirubin monoglucuronide, which is then further conjugated to form bilirubin diglucuronide. However, in obstructive jaundice, the obstruction prevents the conversion of bilirubin monoglucuronide to bilirubin diglucuronide, leading to an increase in bilirubin monoglucuronide levels.