Biochemistry
Extracellular Matrix
Extracellular matrix for MBBS: collagen and elastin, glycosaminoglycans and proteoglycans, scurvy and mucopolysaccharidoses, and protein sorting, mapped to NMC codes BI9.1 to BI9.3.
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Extracellular Matrix
Extracellular matrix for MBBS: collagen and elastin, glycosaminoglycans and proteoglycans, scurvy and mucopolysaccharidoses, and protein sorting, mapped to NMC codes BI9.1 to BI9.3.
The extracellular matrix chapter covers the material that surrounds and supports cells. It describes collagen, elastin, glycosaminoglycans and proteoglycans, the vitamin-dependent steps in their synthesis, and the disorders, from scurvy to the mucopolysaccharidoses, that arise when these components are faulty.
High-yield: Extracellular Matrix
- The extracellular matrix is made of fibrous proteins such as collagen and elastin embedded in a ground substance of proteoglycans.
- Collagen is the most abundant protein in the body and has a characteristic triple-helix built on a repeating glycine-X-Y sequence.
- Every third residue of collagen is glycine, the smallest amino acid, which allows tight packing of the triple helix.
- Hydroxylation of proline and lysine in collagen requires vitamin C as a cofactor for the hydroxylase enzymes.
- Vitamin C deficiency causes scurvy, with poor wound healing, bleeding gums and fragile blood vessels from defective collagen.
- Osteogenesis imperfecta is a defect of type I collagen, giving brittle bones and blue sclerae.
- Ehlers-Danlos syndrome arises from defects in collagen structure or processing, causing hyperextensible skin and hypermobile joints.
- Elastin gives tissues their recoil and is cross-linked through desmosine formed from lysine residues.
- Alpha-1-antitrypsin deficiency allows unopposed elastase to destroy lung elastin, causing early emphysema.
- Glycosaminoglycans are long repeating disaccharides that are highly negatively charged and hold water in the matrix.
- Proteoglycans, glycosaminoglycans attached to a core protein, resist compression in cartilage.
- Mucopolysaccharidoses such as Hurler and Hunter syndrome result from failure to degrade glycosaminoglycans.
- Protein targeting sorts newly made proteins to their correct destination using signal sequences.
- I-cell disease results from failure to add the mannose-6-phosphate tag, so lysosomal enzymes are wrongly secreted instead of delivered to lysosomes.
Matrix components and disorders
- **Collagen:** Triple helix, glycine every third residue. Needs vitamin C. Defects: scurvy, osteogenesis imperfecta.
- **Elastin:** Provides recoil, cross-linked by desmosine. Emphysema in alpha-1-antitrypsin deficiency.
- **Glycosaminoglycans:** Negatively charged, hold water. Accumulate in mucopolysaccharidoses.
- **Protein sorting:** Mannose-6-phosphate tag targets lysosomal enzymes. Faulty in I-cell disease.
NMC competencies in this chapter
- **BI9.1:** Functions and components of the extracellular matrix
- **BI9.2:** Involvement of extracellular matrix components in health and disease
- **BI9.3:** Protein targeting and sorting and its associated disorders
Frequently Asked Questions
Why is vitamin C needed for collagen?
Vitamin C is a cofactor for the enzymes that hydroxylate proline and lysine in collagen. Without it the triple helix is unstable, which is why scurvy causes weak connective tissue and poor wound healing.
Why is glycine found at every third position in collagen?
Glycine is the smallest amino acid, so it fits into the crowded core of the tightly wound triple helix. Substituting a larger residue, as in osteogenesis imperfecta, disrupts the structure.
What are the mucopolysaccharidoses?
They are inherited disorders in which enzymes that break down glycosaminoglycans are deficient, so these molecules accumulate. Examples include Hurler and Hunter syndromes.
What goes wrong in I-cell disease?
The mannose-6-phosphate tag that directs enzymes to lysosomes is not added, so lysosomal enzymes are secreted out of the cell instead. Undigested material then builds up inside inclusion bodies.
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