Topic 3 (Proteins Health) Flashcards
What type of proteins contain keratin/collagen
Fibrous proteins
What type of proteins have repeated AA sequences and have a high hydrophobic AA content
Fibrous proteins
What type of proteins are soluble
Globular
What % of abnormal haemoglobins is caused by a single AA change?
95%
Whats the role of myoglobion?
Stores O2 in tissue
Where is myoglobin found predominantly
skeletal / cardiac muscle
Structure of myoglobin (helices)
8 a-helices
What group does myoglobin contain?
What does this comprise of (2)
Haem prosthetic group
Fe(2+) + Protoporphyrin IX
What is haem comprise of? What bonds are present?
9 ring
Covalent bonds
What does Proximal Histidine bind to?
What number/symbol is it denoted?
Binds to Iron
F8
What does Distal Histidine bind to?
What number/symbol is it denoted?
Binds to O2
E7
When Oxygen binds to haem, what moves?
Iron moves closer to E7
Structure of Haemoglobin (a/b)
How is it all held together by?
How many O2 can it carry
2a / 2b
non covalent bonds
4O2
By how much does haemoglobin differ to myoglobin
Differs by 83% AA
What type of protein is haemoglobin in regards to the fact it changes shape
Allosteric
Which protein has a higher affinity for oxygen
Myoglobin
When haemoglobin binds to Oxygen, conformational changes occur which ruptures what?
What does this allow?
Salt bridges rupture
Increases affinity for O2
Which state of haemoglobin is tense and has low affinity for oxygen
What type of bonds are present
T state
Many salt bridges
The Bohr effect is based off what principle?
Decreasing pH = Decreases affinity for O2
When H+ are high, what AA is protonated?
What does this prevent
Histidine residues are protonated
Removes affinity for O2
When H+ is high, what type of AA are protonated?
What does this cause?
+ charged AA
Forms salt bridges = T state = decreases affinity for O2
BPG stands for what?
Where is it found in high concentrations
Biphosphoglycerate
Erythrocytes
How is BPG increased?
hypoxia / high altitudes
What does BPG do to haemoglobin?
Decreaes affinity for O2
How does BPG work?
Binds only in T state to B subunits
-charge on BPG reacts with +AA residues
Foetal HB structure
a2y2 (HbF)
Out of haemoglobin / myoglobin / Foetal Hb, which has the strongest affinity to O2
HbF
Give 2 examples of haemoglobinopathies
Sickle cell
B thalassaemia
What are the two positions that are a critical AA involved with haem functioning correctly (haem contact)
Phe // Leu (hydrophobic)
CD1 / F4
What type of substitution still allows funcitoning haemoglobin?
Conservative substitution
If Alanine is substituted for isoleucine, what occurs in haemoglobin?
Nothing… both are hydrophobic
If Leucine is substituted by Lysine, what occurs in haemoglobin?
Major effect on structure / function
Which type of collagen are most common?
types 1/2/3
Which type of collagen are found in the basal lamina?
Types 4/7
which type of collagen are fibril associated collagens?
Types 5,9, 12
Polypeptide synthesis of collagen occurs in which cell?
Fibroblasts
What sort of structure is formed before being secreted out of cell?
Procollagen triple helical cable
Which type of collagen has extension proteins?
Procollagen
What is cleaved off in procollagen? Where is this done?
Extension peptides
Extracellular spaces of CT
What forms microfibrils?
Tropocollagen
Which AA is repeated every 3rd residue?
Glycine
What modified AA are present in collagen?
What process is done to modify these AA?
Hydroxyproline // Hydroxylysine
Hydroxylation
When does Hydroxylation occur?
Before Polypeptide chain forms a helix
Role of Hydroxyproline?
Stabilises triple helix via H bond formation
Role of Hydroxylysine?
Attachment sites for sugar residues
What handed helix is each individual chain in collagen?
What is the overall direction of tropocollagen?
Left handed helix
Forms right handed twist
Glycine is found where in the helix?
Packed into centre of chain
Where do disulphide bonds form in assembly of collagen?
Between C terminal extensions
What is role of lysyl oxidase / allysine oxidase in collagen production?
Stabilising fibrils from tropocollagen via covalent cross links
Holes between tropocollagen fibres form what?
Nucleation sites for Ca deposition
Role of collagenases?
Repair breakdown of collagen
What are collagenases?
Metalloproteinases
Where are collageneases found in high volume?
Tumour cells for invasion / metastasis
What contracture produces excess collagen in hand
Dupuytrens contracture
What treatment can be given for Dupuytrens contracture
Injection of collagenases
Ehlers Danlos syndrome is caused by what?
Lysyl oxidase deficiency
Symptoms of Ehlers Danlos Syndrome (4)
Joint hypermobility
extreme fatigue
stretchy skin
digestive problems
Osteogenesis is caused by what?
Spontaneous mutation in type 1 collagen
which type of osteogenesis is the worst for prognosis
Type 4
