(Dr. Choy) (Unit A) Topic Note 4 Flashcards
What does the value of dissociation constant (K) imply?
- Low K = Ligand has high affinity for binding
- High K = Ligand has low affinity for binding
What is the shape of myoglobin?
- Single polypeptide
- 8 alpha-helices
- A single molecule of heme
What is the structure of hemoglobin?
- Four polypeptides (2 alpha subunits and 2 beta subunits)
- Four heme groups
What is myoglobin responsible for?
- Present in muscles
- Helps to distribute oxygen delivered by the bloodstream throughout muscle tissue
What is hemoglobin responsible for?
- Present in RBCs
- Binds to oxygen in the lungs
- Transports oxygen through the bloodstream and delivers to tissues
What two states does hemoglobin exist in?
- Tense (T): Deoxygenated
- Relaxed (R): Oxygenated
When initially binding to oxygen, what is hemoglobin like?
In the T-state, binds to oxygen relatively weakly
Once bound to the oxygen, what happens to the hemoglobin?
Conformation change occurs and the hemoglobin changes to R form allowing for 3 more oxygens to bind
Why does hemoglobin have a S-shaped curve?
Allows oxygen to bind tightly enough to be carried, but still loose to allow for release into the muscles
What is oxygen-binding influenced by?
- Higher concentration of CO2
- Lower pH in the tissues
- Presence of bisphosphoglycerate (BPG) in RBCs
What is the effect of pH on oxygen binding to hemoglobin known as?
Bohr Effect
What is collagen?
- Fibrous protein
- Forms very strong fibrils
- Strengthen bone, skin and basement membranes of arteries, veins and many other tissues
Is collagen one single protein?
It is a family of proteins
* Collagen I
* Collagen II
* Collagen III
* Collagen IV
How is collagen amino acid composition unusual?
All 20 amino acids are present, but:
* Rich in glycine
* High proline content
How rich in glycine is collagen?
Every third amino acid residue in the sequence is glycine
What amino acids are modified by hydroxylation in collagen?
- Many prolines, giving hydroxyproline
- Some lysines, giving hydroxylysines
How does collagen construction start?
Synthesis of an individual polypeptide
* Different lengths
* Often quite long (1000 residues)
Does the initial polypeptide of collagen have N and C terminals?
Yes, but they are later removed
* Becomes propeptides
Once the collagen chains are formed and become propeptides, what happens?
Hydroxylated in the endoplasmic reticulum
* Carried out by two different enzymes (one of them is prolyl hydroxylase)
Why the deficiency of vitamin C affect collagen formation?
The enzyme required in collagen formation - prolyl hydroxylase - requires vitamin C to be functional
After the chains are hydroxylated, what happens to collagen?
3 collagen strands assemble together
* Starts by associating at the C-terminal propeptide region
What is the initial coiled structure of collagen known as? What characteristic does it have?
Procollagen
* Has uncoiled, frayed ends
How can the 3 chains come so close together in procollagen?
- Hydrogen bonds between hydroxyl groups of hydroxyproline
- Small side chain of glycine at every third residue
Does collagen form an alpha helix structure?
No, it forms a much more extended helical conformation
Why are hydroxylysine residues necessary?
Sites of sugar addition that increase solubility
What are sites of sugar addition known as?
Glycosylation
What does lysyl oxidase do?
Modifies lysine to form allysine
What does allysine do?
Participates in cross-linking reactions that create covalent bonds between collagen chains
How is procollagen modified to have only the triple-stranded rope part?
Propeptides are trimmed off by specific proteases to leave only the triple-stranded rope part
What is the trimmed procollagen known as?
Tropocollagen
How does the collagen fibrils form?
Tropocollagen molecule assembles into ordered polymers
Why is the final collagen fiber extremely strong?
Covalent crosslinks are formed between neighboring molecules
