Untitled Quiz

Conversion of Amino Acids to Specialized Products

• Dietary protein intake is typically 100 g/day in the U.S.
• Body protein is approximately 400 g/day.
• Synthesis of nonessential amino acids varies
• Amino acid pool is approximately 30 g/day.
• Specialized products include porphyrins, creatine, neurotransmitters, purines, pyrimidines, and other nitrogen-containing compounds.

Porphyrins

• Cyclic compounds that bind metal ions (ferrous or ferric).
• Composed of four pyrrole rings.
• Form complexes with metal ions bound to the nitrogen atom of the pyrrole ring.

Properties of Methenyl Group

• Methenyl bridge (oxidized form) - (-HC-).
• Methylene bridge (reduced form) - (-CH2-).
• Porphyrin's methenyl groups can be oxidized or reduced.

Porphyrin Structure

• Side chains attached to pyrrole rings vary.
  • Uroporphyrin I has acetate and propionate side chains.
  • Coproporphyrin has methyl and propionate side chains.
  • Protoporphyrin IX has methyl, vinyl, and propionate side chains.
• Porphyrins with Type III structure are most important in humans.

Hemeproteins

• Hemoglobin: Transports oxygen in blood.
• Myoglobin: Stores oxygen in muscle.
• Cytochrome c: Involved in electron transport chain.
• Cytochrome P450: Hydroxylates xenobiotics.
• Catalase: Degrades hydrogen peroxide.
• Tryptophan pyrrolase: Oxidizes tryptophan.

Heme Structure

• Ferrous iron (Fe2+).
• Protoporphyrin IX: Contains tetrapyrrole rings linked by methenyl bridges.
• Side chains: Methyl (M), Vinyl (V), and Propionyl (P).

Heme Biosynthesis Location

• Hepatocytes synthesize approximately 15% of heme proteins, specifically cytochrome P450.
• Erythrocyte-producing cells in bone marrow synthesize about 85% of heme, crucial for hemoglobin synthesis.
• Heme biosynthesis occurs in both mitochondria and cytosol, with the pathway starting and ending in mitochondria.

Heme Synthesis Steps

• Steps 1 and 2: Formation of a pyrrole molecule (containing 4 carbon atoms and 1 nitrogen atom, in a ring structure).
• Step 3: Linkage of four pyrrole molecules to form a linear tetrapyrrole.
• Step 4: Formation of the porphyrin (tetrapyrrole) ring.
• Steps 5-7: Decarboxylation and oxidation.
• Step 8: Incorporation of the iron atom.

First Step in Heme Pathway

• Condensation reaction between glycine (nonessential amino acid) and succinyl CoA (intermediate from the TCA cycle).
• Catalyzed by mitochondrial enzyme aminolevulinic acid synthase (ALAS), which requires coenzyme PLP.
• Rate-limiting step in heme synthesis.
• Two isoforms, ALA-S1 (present in all tissues) and ALA-S2 (produced in erythroid tissue).

Porphyria ("Vampire Disease")

• Rare metabolic diseases resulting from enzyme defects in heme biosynthesis.
• Accumulation of porphyrins or precursors.
• Classified as hepatic porphyria (chronic or acute) or erythropoietic porphyria.

Degradation of Heme

• About 80-85% of heme originates from red blood cells (RBCs).
• Location of heme degradation: Macrophage systems in the liver and spleen.
• Key products of heme degradation:
  • Iron is returned to body stores.
  • Globin is broken down into amino acids.
  • Bilirubin is formed from the porphyrin ring.
• Microsomal heme oxygenase in macrophages catalyzes three oxygenations.
  • Formation of biliverdin
  • Release of iron (Fe+3)
  • Release of carbon monoxide (CO)
  • Biliverdin is then reduced to bilirubin by biliverdin reductase.

Bilirubin Metabolism

• Transferred to the liver as a bilirubin-albumin complex.
• Dissociates from albumin and binds to ligandin.
• Conjugation with glucuronic acid (via UDP glucuronyl transferase), which increases solubility.
• Conjugated bilirubin (CB) is secreted into bile.

Disorders Linked to Heme Degradation

• Jaundice: Yellowing of skin and eyes caused by bilirubin buildup in the blood.
  • Prehepatic jaundice: Hemolysis.
  • Hepatocellular jaundice: Liver damage.
  • Post-hepatic jaundice: Obstruction of the bile duct.
• Types of jaundice and causes are included.

Catecholamines

• Biologically active water-soluble amines derived from tyrosine.
• Neurotransmitters in the CNS.
• Hormones in circulation, responding to stress or hypoglycemia.
• Synthesized in the brain and adrenal medulla.
• Include Dopamine, Norepinephrine, and Epinephrine.
• Regulate carbohydrate and lipid metabolism.
• Released in response to stress, exercise, cold, or low blood glucose.
  • Increase glycogen and triacylglycerol breakdown.
  • Increase blood pressure and heart output.

Melanin

• Pigment found in the eyes, hair, and skin.
• Synthesized from tyrosine by melanocytes.
• Protects cells from sunlight.
• Albinism (a genetic disorder) results from melanin production defects due to copper deficiencies.

Creatine Synthesis

• Amidinotransferase: Rate-limiting enzyme in the mitochondrial pathway of creatine synthesis.
• Methyltransferase uses SAM (S-adenosyl methionine) as a one-carbon donor to produce creatine.
• Creatine kinase: Catalyzes phosphorylation of creatine using ATP (provides the phosphate).
• Creatinine (breakdown product): Excreted in urine; measurement is used to assess kidney function.