Properties

The physical and chemical properties of heme derivatives are essential for their function in oxygen transport, electron transfer, and detoxification

Hemoglobin

Definition: A protein found in red blood cells responsible for transporting oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs
Structure
- Tetrameric Protein: Consists of four polypeptide chains (globins)
- Two α Chains and Two β Chains: In adult hemoglobin (HbA), each chain is linked to a heme group
- Heme Group: A porphyrin ring with a central iron atom (Fe2+ in the functional state)
Physical Properties
- Color: Red when oxygenated (oxyhemoglobin), bluish-red when deoxygenated (deoxyhemoglobin)
- Solubility: Soluble in water within red blood cells
- Molecular Weight: Approximately 64,000 Da
- Quaternary Structure: Tetrameric structure allows for cooperative binding of oxygen
Chemical Properties
- Oxygen Binding: Iron atom in heme binds reversibly to oxygen
  - Oxyhemoglobin: Hemoglobin bound to oxygen
  - Deoxyhemoglobin: Hemoglobin without oxygen
- Carbon Dioxide Binding: Hemoglobin can also bind to carbon dioxide and transport it back to the lungs
- Allosteric Regulation: Oxygen binding is affected by pH, carbon dioxide, and 2,3-bisphosphoglycerate (2,3-BPG)
- Methemoglobin Formation: Iron can be oxidized to Fe3+, forming methemoglobin, which cannot bind oxygen
- Carbaminohemoglobin Formation: Carbon dioxide can bind to amino groups in hemoglobin, forming carbaminohemoglobin

Definition: A protein found in muscle cells that stores oxygen and facilitates oxygen diffusion
Structure
- Monomeric Protein: Consists of a single polypeptide chain (globin)
- Heme Group: A porphyrin ring with a central iron atom (Fe2+ in the functional state)
Physical Properties
- Color: Red
- Solubility: Soluble in water within muscle cells
- Molecular Weight: Approximately 17,000 Da
- Tertiary Structure: Globular protein with a hydrophobic pocket for the heme group
Chemical Properties
- Oxygen Binding: Iron atom in heme binds reversibly to oxygen
  - Oxymyoglobin: Myoglobin bound to oxygen
  - Deoxymyoglobin: Myoglobin without oxygen
- Higher Oxygen Affinity: Myoglobin has a higher affinity for oxygen than hemoglobin, allowing it to store oxygen in muscles
- Not Affected by Allosteric Regulators: Oxygen binding is not significantly affected by pH, carbon dioxide, or 2,3-BPG

Definition: A yellow pigment produced from the breakdown of heme
Types
- Unconjugated Bilirubin (Indirect): Insoluble in water, transported in blood bound to albumin
- Conjugated Bilirubin (Direct): Water-soluble, conjugated with glucuronic acid in the liver
Structure
- Tetrapyrrole Ring: A linear chain of four pyrrole rings
Physical Properties
- Color: Yellow
- Solubility:
  - Unconjugated: Insoluble in water
  - Conjugated: Soluble in water
- Light Sensitivity: Bilirubin is degraded by light
Chemical Properties
- Formation from Heme: Produced by heme oxygenase and biliverdin reductase
- Conjugation: Conjugated with glucuronic acid by UDP-glucuronosyltransferase (UGT) in the liver, making it water-soluble
- Excretion: Secreted into bile and excreted in feces
- Diazo Reaction: Reacts with diazonium salts to form a colored product (used in laboratory assays)
- Phototherapy: Blue light converts bilirubin to more soluble isomers that can be excreted in urine (used in treating neonatal jaundice)

Definition: A colorless compound produced in the intestine by bacterial reduction of bilirubin
Structure
- Tetrapyrrole Ring: Similar to bilirubin, but more reduced
Physical Properties
- Color: Colorless
- Solubility: Soluble in water
Chemical Properties
- Formation from Bilirubin: Produced by bacterial reduction of bilirubin in the intestine
- Oxidation to Urobilin: Urobilinogen can be oxidized to urobilin, a brown pigment
- Excretion:
  - Most of the urobilinogen is excreted in feces as stercobilin (gives feces its brown color)
  - A small amount is reabsorbed and excreted in urine as urobilin (gives urine its yellow color)
- Ehrlich’s Reagent: Reacts with Ehrlich’s reagent (p-dimethylaminobenzaldehyde) to form a colored product (used in laboratory assays)

Definition: A group of cyclic tetrapyrrole compounds that are intermediates in heme synthesis
Types
- Uroporphyrin
- Coproporphyrin
- Protoporphyrin
Structure
- Cyclic Tetrapyrrole Ring: Four pyrrole rings linked by methene bridges
Physical Properties
- Color: Highly colored compounds, exhibiting fluorescence
- Solubility: Varies depending on the specific porphyrin and its substituents
Chemical Properties
- Heme Precursors: Intermediates in the synthesis of heme
- Metal Binding: Can bind to metal ions, such as iron
- Fluorescence: Exhibit fluorescence under UV light, allowing for detection and quantification
- Acid Extraction: Can be extracted from biological samples using acidic solutions
- Porphyria Markers: Accumulation of specific porphyrins in urine, blood, or feces is indicative of porphyria

Heme Derivative	Structure	Physical Properties	Chemical Properties
Hemoglobin	Tetrameric Protein + 4 Heme	Red (oxygenated), Soluble	Oxygen Binding, CO2 Binding, Allosteric Regulation, Methemoglobin Formation, Carbaminohemoglobin Formation
Myoglobin	Monomeric Protein + Heme	Red, Soluble	Oxygen Binding (Higher Affinity), Not Affected by Allosteric Regulators
Bilirubin	Tetrapyrrole Ring	Yellow, Insoluble (Unconjugated), Soluble (Conjugated)	Formation from Heme, Conjugation, Excretion, Diazo Reaction, Phototherapy
Urobilinogen	Tetrapyrrole Ring	Colorless, Soluble	Formation from Bilirubin, Oxidation to Urobilin, Excretion, Ehrlich’s Reagent
Porphyrins	Cyclic Tetrapyrrole Ring	Highly Colored, Fluorescent	Heme Precursors, Metal Binding, Fluorescence, Acid Extraction, Porphyria Markers

Heme: A porphyrin ring complex with a central iron atom
Hemoglobin: The protein in red blood cells that transports oxygen
Myoglobin: The protein in muscle cells that stores oxygen
Bilirubin: A yellow pigment produced from the breakdown of heme
Urobilinogen: A colorless compound produced in the intestine by bacterial reduction of bilirubin
Porphyrins: Cyclic tetrapyrrole compounds that are intermediates in heme synthesis
Oxyhemoglobin: Hemoglobin bound to oxygen
Deoxyhemoglobin: Hemoglobin without oxygen
Unconjugated Bilirubin: Bilirubin that has not been conjugated in the liver
Conjugated Bilirubin: Bilirubin that has been conjugated in the liver
Porphyria: A genetic disorder caused by deficiencies in enzymes of the heme synthesis pathway