Biochemistry of Melanin and Serotonin

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Questions and Answers

What is the function of melanin in cells?

To regulate body temperature

To protect cells from harmful effects of sunlight (correct)

To enhance nutrient absorption

To improve oxygen levels in the body

What causes albinism in individuals?

Lack of vitamin D synthesis

Defect in copper-containing tyrosinase (correct)

Increased production of dopamine

Excessive melanin degradation

Where is serotonin predominantly synthesized in the body?

In the brain

In the liver

In the kidneys

In the GI tract (correct)

What is the primary precursor for serotonin synthesis?

Tryptophan Signup and view all the answers

Which enzyme is responsible for the oxidative degradation of catecholamines?

Monoamine oxidase (MAO) Signup and view all the answers

Which enzyme catalyzes the rate-limiting step in creatine synthesis?

Amidinotransferase Signup and view all the answers

What role does catechol-O-methyltransferase (COMT) play in catecholamine metabolism?

It methylates catecholamines using S-adenosylmethionine Signup and view all the answers

What is the role of methyltransferase in creatine synthesis?

To yield creatine using S-Adenosylmethionine Signup and view all the answers

What type of reactions does histamine mediate?

Cellular responses including allergic and inflammatory reactions Signup and view all the answers

What happens to creatine and creatine phosphate during degradation?

They cyclize to form creatinine Signup and view all the answers

Which porphyrin structure includes acetate and propionate side chains?

Uroporphyrin I Signup and view all the answers

What percentage of heme proteins is synthesized in hepatocytes?

15% Signup and view all the answers

Which of the following metals can bind to porphyrins?

Ferrous or ferric ion Signup and view all the answers

What is the first step that microsomal heme oxygenase catalyzes in the degradation of heme?

Open porphyrin ring to form biliverdin Signup and view all the answers

What does bilirubin bind to when it is transported to the liver?

Albumin Signup and view all the answers

What is a distinguishing feature of Type III porphyrins in humans?

They are asymmetric. Signup and view all the answers

Where does the majority of heme synthesis occur in the human body?

Erythroid tissue Signup and view all the answers

Which substance is produced from the further processing of biliverdin?

Bilirubin Signup and view all the answers

In what form is bilirubin made soluble for excretion?

Conjugated with glucuronic acid Signup and view all the answers

Which amino acid structure is NOT a part of protoporphyrin IX?

Acetate Signup and view all the answers

What characterizes prehepatic jaundice?

Excessive bilirubin production due to hemolysis Signup and view all the answers

Which statement about erythrocyte-producing cells is true?

They have a constant rate of heme synthesis. Signup and view all the answers

What is NOT a product of the intestinal bacteria during bilirubin metabolism?

Conjugated bilirubin Signup and view all the answers

What is the function of the methenyl bridges in protoporphyrin IX?

They connect the pyrrole rings. Signup and view all the answers

What is the normal bilirubin level in blood considered to be non-elevated?

< 1 mg/dl Signup and view all the answers

How is bilirubin commonly excreted from the body?

In the urine as urobilin Signup and view all the answers

What is primarily increased in the blood due to massive hemolysis?

Unconjugated bilirubin Signup and view all the answers

What is a common consequence of hepatocellular damage?

Increased unconjugated bilirubin in blood Signup and view all the answers

What causes dark urine and pale clay-colored stools in post-hepatic jaundice?

Obstruction of the bile duct Signup and view all the answers

What is the primary reason for elevated bilirubin in newborns during the first week of life?

Low levels of bilirubin UGT enzyme Signup and view all the answers

Which of the following catecholamines is synthesized in the adrenal medulla?

Epinephrine Signup and view all the answers

What role do catecholamines play in metabolism during stress responses?

Regulate carbohydrate and lipid metabolism Signup and view all the answers

What pigment is synthesized from tyrosine in the epidermis?

Melanin Signup and view all the answers

What is the effect of blue fluorescent light therapy on elevated bilirubin in newborns?

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

Which type of porphyria is most commonly associated with chronic liver disease?

Porphyria cutanea tarda Signup and view all the answers

What is the major consequence of the accumulation of porphyrins in patients with hepatic porphyria?

Photosensitivity Signup and view all the answers

In acute hepatic porphyria (AIP), which compound is primarily accumulated?

Porphobilinogen Signup and view all the answers

Where does the majority of heme degradation occur in the body?

Liver and spleen Signup and view all the answers

Which enzyme is responsible for the conversion of aminolevulinic acid (ALA) in heme synthesis?

ALA dehydratase Signup and view all the answers

What is the main clinical sign noted in patients with acute intermittent porphyria?

Dark red urine Signup and view all the answers

What substance is mainly derived from the degradation of hemoglobin in red blood cells?

Heme Signup and view all the answers

What is the role of ferrochelatase in heme synthesis?

It converts protoporphyrin into heme Signup and view all the answers

Which condition is characterized by the skin's reaction to UV light due to porphyrin accumulation?

Porphyria cutanea tarda Signup and view all the answers

Which of the following best describes erythropoietic porphyria?

Often presents with photosensitivity Signup and view all the answers

Study Notes

Conversion of amino acids to specialized products

Dietary protein intake is typically 100g/day in the US.
Body protein is approximately 400g/day.
Amino acid pool synthesis is about 30g/day.
Synthesis of specialized products from amino acids includes porphyrins, creatine, neurotransmitters, purines, pyrimidines, and other nitrogen-containing compounds.
Nucleic acid metabolism is involved.
Glucose, glycogen, ketone bodies, fatty acids, and steroids are produced.

Porphyrins

Porphyrins are cyclic compounds readily binding ferrous or ferric ions.
They comprise four pyrrole rings.
The formation of complexes with metal ions involves nitrogen atoms in the pyrrole ring.

Properties of methenyl group

A methenyl bridge is an oxidized form.
A methylene bridge is a reduced form.

Porphyrin Side Chains

Uroporphyrin I has acetate and propionate side chains.
Coproporphyrin has methyl and propionate side chains.
Protoporphyrin IX has methyl, vinyl, and propionate side chains.

Porphyrin Side Chains Distribution

Only type III porphyrins are important for humans.
Porphyrin contains four pyrrole rings (A, B, C, and D), joined by methenyl bridges.
Uroporphyrin I shows symmetrical arrangement of side chains.
Coproporphyrin and Uroporphyrin III are asymmetrical.

Hemeproteins

Hemoglobin transports oxygen in the blood.
Myoglobin stores oxygen in muscle.
Cytochrome c is part of electron transport chains.
Cytochrome P450 is involved in the hydroxylation of xenobiotics.
Catalase degrades hydrogen peroxide.
Tryptophan pyrrolase oxidizes tryptophan.

Structure of Heme

Heme contains ferrous iron (Fe2+).
Protoporphyrin IX contains four pyrrole rings linked by methenyl bridges.
The side chains are: methyl (M), vinyl (V), and propionyl (P).

Heme Biosynthesis Location

Hepatocytes synthesize about 15% of heme proteins, particularly cytochrome P450.
Erythrocyte-producing cells in bone marrow synthesize about 85% of heme.
The rate of synthesis is variable.
Heme biosynthesis occurs in mitochondria and cytosol.

Heme Synthesis Steps

Steps 1 and 2 form a pyrrole molecule: a compound containing four carbon atoms and one nitrogen atom joined in a ring structure.
Step 3 links four pyrrole molecules to form a linear tetramer.
Step 4 forms the porphyrin (tetrapyrrole) ring.
Steps 5-7 involve decarboxylation and oxidation.
Step 8 incorporates the iron atom.

First Step in Heme Pathway

Heme pathway's first step is a committed step.
It involves a condensation reaction between glycine and succinyl CoA.
The reaction is catalyzed by the mitochondrial enzyme aminolevulinic acid synthase (ALAS).
ALAS requires coenzyme PLP.
This is a rate-limiting step.
Two isoforms of ALAS exist, ALA-S1 located in all tissues, and ALA-S2 in erythroid tissues.

Porphyria (Vampire Disease)

Porphyrias are rare metabolic diseases that can result in a defect (deficiency) in heme biosynthesis.
Deficiency results in the accumulation of porphyrins or porphyrin precursors.
It's classified as hepatic porphyria (chronic or acute) and erythropoietic porphyria.

Chronic Hepatic Porphyria or Porphyria Cutanea Tarda (PCT)

This is the most common porphyria.
Patients are photosensitive and often have chronic liver disease.
The disease causes a buildup of porphyrins in the body, leading to the production and excretion of red-brown urine.
Porphyria cutanea tarda (PCT) is often linked to alcohol use.

Acute Hepatic Porphyria or Acute Intermittent Porphyria (AIP)

AIP leads to the buildup of porphobilinogen in the blood and urine.
This can cause severe abdominal pain, neurological symptoms, and seizures.

Degradation of Heme

About 80-85% of heme comes from red blood cells.
Degradation occurs in the reticuloendothelial system of the liver and spleen.
Heme is broken down into iron, bilirubin, and globin.
Microsomal heme oxygenase is an enzyme within the macrophage system catalyzing three oxygenations.
- The first oxygenation opens the porphyrin ring.
- The second releases iron.
- The third releases carbon monoxide.
Biliverdin is reduced to bilirubin by biliverdin reductase.
Bilirubin is transported to the liver.
Conjugation with glucuronic acid makes bilirubin water-soluble, allowing excretion in bile.
Unconjugated bilirubin isn't secreted.

Jaundice

Jaundice is a clinical syndrome leading to yellowing of skin, nails, and sclerae caused by elevated bilirubin levels.
- A buildup of bilirubin.
- Different types of jaundice (prehepatic, hepatic, posthepatic) are associated with various causes.

Types of Jaundice

Prehepatic (hemolytic) jaundice: excessive red blood cell breakdown causes high unconjugated bilirubin levels.
Hepatic jaundice: liver damage impairs bilirubin conjugation, leading to increased unconjugated or conjugated bilirubin.
Posthepatic (obstructive) jaundice: obstruction of bile ducts prevents bilirubin excretion into the gut, leading to increased conjugated bilirubin.

Causes of Hyperbilirubinemia

Hemolytic anemia, hepatitis, and biliary duct stones.

Jaundice in Newborns

Most newborn babies show a rise in unconjugated bilirubin levels in the first week due to lower activity of the enzyme bilirubin UGT.
Elevated unconjugated bilirubin levels can lead to toxic effects and are treated with blue fluorescent light to convert the bilirubin into more polar compounds that are then excreted.

Catecholamines and Melanin

Tyrosine is a precursor for catecholamines and melanin.
Phenylalanine is a precursor for melanin.
Catecholamines are biologically active water-soluble amines derived from tyrosine.
They serve as neurotransmitters in the central nervous system (CNS) and hormones during stress response.
Examples are dopamine, norepinephrine, and epinephrine.
Melanin is a pigment found in skin, hair, and eyes, protecting from sunlight.

Synthesis of Melanin

It's synthesized from tyrosine by melanocytes in the epidermis.
Defects in melanin production lead to albinism.

Degradation of Catecholamines

Catecholamines have a short half-life and are inactivated by enzymes such as MAO and COMT.
Common breakdown products include dihydroxymandelic acid, metanephrine, normetanephrine, and vanillylmandelic acid.

Histamine Synthesis

Histamine is a chemical messenger involved in allergic, inflammatory, and gastric acid secretion responses.
It's synthesized from histidine by histidine decarboxylase, requiring pyridoxal phosphate (PLP).
Mast cells secrete histamine in response to trauma or allergic reactions.

Serotonin Synthesis

Serotonin (5-hydroxytryptamine) is produced predominantly in the gastrointestinal tract.
It's synthesized from tryptophan.
It's inactivated by MAO.
It's involved in various physiologic processes.

Creatine Synthesis

Amidinotransferase is a mitochondrial enzyme essential in creatine synthesis.
Methyltransferase uses S-adenosylmethionine as a one-carbon donor for creatine synthesis.
Creatine kinase catalyzes the phosphorylation of creatine, using ATP as a phosphate donor.
Degradation involves spontaneous cyclization of creatine/creatine phosphate creating creatinine.
Serum creatinine levels in the blood commonly used to diagnose kidney issues.

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Explore the fascinating functions of melanin and serotonin within the body through this quiz. Test your knowledge on their synthesis, degradation, and related metabolic processes. Ideal for students focusing on biochemistry and cellular biology.