Myoglobin Human
Description
Biochemical Characteristics
Myoglobin Human is a 153-amino-acid protein with a molecular weight of 17.67 kDa (non-glycosylated) . Its core structure includes:
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Heme group: A porphyrin ring coordinated to a ferrous iron (Fe²⁺) atom, enabling reversible oxygen binding .
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Protein fold: Eight α-helices (A–H) arranged in a globular structure, forming a hydrophobic pocket for heme sequestration .
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Key residues: Proximal histidine (His-93) coordinates the heme iron, while distal residues (e.g., His-64) stabilize O₂ binding .
Table 2: Myoglobin Content in Human Tissues
| Tissue Type | Myoglobin Concentration (μmol/g) |
|---|---|
| Cardiac muscle | 1.2–2.0 |
| Oxidative skeletal muscle (Type I) | 0.8–1.5 |
| Mixed skeletal muscle (Type II) | 0.2–0.5 |
| Smooth muscle | Trace |
Nitric Oxide (NO) Scavenging
Myoglobin binds nitric oxide, modulating vascular tone and mitigating oxidative stress . Mutations altering heme dynamics (e.g., p.His98Tyr) increase heme instability and reactive oxygen species (ROS) production, linking Myoglobin to oxidative stress-related pathologies .
Myoglobinopathy
A novel autosomal dominant myopathy caused by the p.His98Tyr mutation in MB disrupts O₂ binding and heme stability. Key features include:
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Muscle weakness: Proximal and axial involvement progressing to respiratory failure .
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Biochemical defects: Elevated heme loss rate (k-H) and reduced O₂ affinity compared to wild-type .
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Oxidative stress: Increased intracellular superoxide levels in mutant Myoglobin-expressing cells .
Table 3: Functional Consequences of p.His98Tyr Mutation
| Parameter | Wild-Type Myoglobin | Mutant Myoglobin (p.His98Tyr) |
|---|---|---|
| O₂ affinity (P₅₀) | ~2.8 mmHg | Reduced by 30–50% |
| Heme dissociation (k-H) | Low | Increased 5-fold |
| Superoxide levels | Basal | 1.45-fold elevation |
Cancer and Hypoxia
Myoglobin expression is upregulated in hypoxic brain tumors (e.g., glioblastoma) and correlates with aggressive phenotypes . Its role in cancer may involve:
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Hypoxia adaptation: Sustaining O₂ availability in low-oxygen microenvironments .
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Metabolic reprogramming: Potential interaction with lactate dehydrogenase (LDHA) in glycolysis .
Table 4: Myoglobin Expression in Tumors
| Tumor Type | Myoglobin Expression (%) | Hypoxia-Induced Regulation |
|---|---|---|
| Glioblastoma | 70–90 | ↑ (Hypoxia-inducible factor) |
| Breast carcinoma | 50–70 | Variable |
| Renal cell carcinoma | 60–80 | ↑ |
Recombinant Production
Human Myoglobin is produced in E. coli as a non-glycosylated protein (17.67 kDa) with >95% purity . Applications include:
Table 5: Production Methods
| Method | Host System | Yield | Purity |
|---|---|---|---|
| Bacterial expression | E. coli | 10–20 mg/L | >95% |
| Plant-based systems | Nicotiana benthamiana | 0.5–1.0 mg/g | 90% |
Diagnostic Biomarker
Myoglobin serves as a biomarker for muscle injury, with serum levels rising within hours of rhabdomyolysis . Urinary myoglobinuria indicates renal tubular damage .
Future Directions
Emerging research focuses on:
Product Specs
Product Science Overview
Myoglobin is a member of the globin superfamily and is predominantly expressed in skeletal and cardiac muscles. The protein forms a monomeric globular hemoprotein that is primarily responsible for the storage and facilitated transfer of oxygen from the cell membrane to the mitochondria. This protein also plays a role in regulating physiological levels of nitric oxide .
Recombinant human myoglobin is produced using recombinant DNA technology, which involves inserting the human myoglobin gene into a suitable host organism, such as Escherichia coli (E. coli), to produce the protein in large quantities. The recombinant protein is then purified using conventional chromatography techniques .
The recombinant human myoglobin protein typically consists of 160 amino acids and has a predicted molecular mass of approximately 18.01 kDa . It is often formulated in a lyophilized form from a sterile buffer solution containing various protectants to ensure stability during storage and shipping .
Recombinant human myoglobin is widely used in research to study its structure, function, and interactions with other molecules. It serves as a model protein for understanding the mechanisms of oxygen storage and delivery in muscle tissues. Additionally, it is used in various biochemical assays and experiments to investigate its role in regulating nitric oxide levels and its interactions with other proteins involved in cellular respiration .
Mutations or abnormalities in the myoglobin gene can lead to various diseases and conditions. For example, myoglobinopathy is an adult-onset autosomal dominant myopathy characterized by the presence of sarcoplasmic inclusions in muscle cells . Other diseases associated with myoglobin include compartment syndrome and medullomyoblastoma .
