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Biochemistry- Unit One
Proteins- Hemeproteins, Collagens (T Pierce)
47
Medical
Post-Graduate
01/09/2009

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Cards

Term

Describe structure of heme

Definition
  • porphyrin ring
  • contains four pyrrole rings joined via one carbon bridge
  • iron (ferrous) coordinated to four pyrrole nitrogens
Term

Chemical structure of myoglobin

Definition
  • single polypeptide chain
  • heme group that bind oxygen
Term

Three major hemeproteins

Definition

hemoglobin

myoglobin

cytochromes

Term
Six different chains that can be found in hemoglobin
Definition

alpha

beta

gamma

delta

epsilon

zeta

Term

Protein structure of HbA1. how much of adult population has it?

Definition
  • two alpha, two beta
  • 96-98% of adult population
Term
Structure of HbA2.
Definition

FUNCTIONS SAME as HbA1

  • two alpha
  • two delta
Term
Structure of HbF and its functional significance
Definition
  • two alpha
  • two gamma (gives different ability to bind and release oxygen)
Term
What is the main driving force for the binding of hemoglobin to oxygen?
Definition

partial pressue of oxygen (as it increases, the percentage of Hb saturation increases)

Term
Where in the body would the Hb be the most saturated with oxygen? Why?
Definition
  • at the lungs
  • the lungs have the highest partial pressure throughout the body
Term

Describe secondary structure of the beta subunit of hemoglobin

Definition
  • eight helical regions intersperesed into non-helical segments
  • named by letters if helical and non helical is named by the helical regions its in between
Term
Describe secondary structure of of alpha subunit of hemoglobin
Definition

very similar to beta secondary structure, but it lacks the a D helix

Term
describe the tertiary structure of hemoglobin
Definition
  • E and F helices of beta chain fold to form arms of the "V"
  • helix C and segment CD of beta chain fill the area at the open end of the "V"
  • the AA that project into the pocket are hydrophobic in nature, allowing the heme to be inserted here
  • helices A, B, G, H round out bottom of pocket
  • histadine interface with heme group
Term
What are the clinical consequences of one of the R groups in the pocket of Hb being hydrophilic?
Definition
  • water can bind to that R group
  • the water will oxidize ferrous to ferric, form methHb
  • now, the heme cannot bind oxygen
  • leads to anemia
Term
Describe quarternary structure of Hb
Definition
  • ellipsoid shaped tetramer
  • two fold axis of symmetry
    • i can rotate 180 degrees around this axis and one pair of alpha beta would occupy the position vacated by other alpha beta
  • hole runs in between tetramer along this axis
Term
Bonds that hold together the subunits of Hb
Definition
primarily hydrophobic bonding between unlike subunits
Term

How does the structure of Hb change when oxygen binds?

Definition
  1. pulls ferrous back into plane of porphyrin ring
  2. this move F helices of beta subunit, causing confirmational change 
  3. salt linkages between 2,3 BPG and the two beta subunits break
  4. this allows subunits to move in relation to each other, as it is in a more relaxed state
Term
Describe the unique structure of deoxyHb
Definition
  • more tightly packed due to inter and intrachain salt bridges
  • 2,3 BPG sits between two beta chains at top of central cavity and binds to these beta subunits via salt bridges
Term
Why does myoglobin not display coopertivity?
Definition
It only has one polypeptide chain, unlike Hb which has four. This creates an "all or nothing" situation where you dont need to "relax" the entire quarternary structure like you would with Hb.
Term

Explain how sickle cell anemia happens

Definition
  • on the surface of beta subunit, you replace a Glu with a Val (replace hydrophilic AA with hydrophobic, changing solubility)
  • there is a natural hydrophobic patch on the Hb
  • valine will bind with another Hb at that hydrophobic patch when in the deoxygenated form
Term
What is the danger in a mutation that changes AA at the subunit interface?
Definition
These subunits must move between tight and loose confirmations, so if a mutation occurs, it could cause oxygen to bind tighter or looser.
Term

Primary structure of collagen molecule

Definition
  • three polypeptide chain called alpha chains
  • EACH TYPE OF COLLAGEN HAS UNIQUE ALPHA CHAINS (alpha 1 I or alpha 1 VIII)
Term
How do u display two distinct chains in each collagen molecule? three distinct chains
Definition
  • alpha 1 (collage type), alpha 2 (collagen type)
  • alpha 1 (collage type), alpha 2 (collagen type), alpha 3 (collagen type)
Term
Primary structure of type I collagen
Definition

alpha 1 (I)2

alpha 2 (I)

Term
Location in body of type I collagen
Definition
  • bone
  • skin
  • tendons
  • ligaments
Term
Primary structure of type II collagen
Definition
three alpha 1 (II)
Term

Primary structure of type III collagen

Definition
three alpha 1 (III)
Term
Primary structure of type IV collagen
Definition

2 alpha 1 (IV)

one alpha 2 (IV)

Term
Describe secondary structure of procollagen. What allows it to have this structure?
Definition
  • extended helices with three AA per turn and the backbone carbonyl or amides project perpendicular to the axis of helix
  • no intrachain H bonds (due to Gly)
    • 33% Gly
    • 20% Pro (prevents free rotation around alpha carbon)
    • unusual AA's
      • hydroxyproline (especially stabilize quarternary structure)
      • hydroxylysine
Term

Describe quarternary structure of procollagen

Definition
  • globular head and tail
  • supercoiled triple helix
Term
Repeat AA sequence of procollagen
Definition

Gly-X-Y with Gly aligned vertically

X project out toward me

Term
Advantage of havin Glycine at the primary structure level
Definition
  • the glycines can tightly pack together at the monomer level, PREVENTING INTRACHAIN hydrogen bonding
  • once in a trimer, get INTERCHAIN hydrogen bonding
Term

Type I collagen has very little sugar and hydroxylysine. What is the structural consequence of this?

Definition
forms broad fibers
Term
Describe quarternary structure of type IV collagen
Definition
  • does not form fibrillar structure
  • Gly-X-Y repaeat is interrupted, leading to kinks which produce areas of flexibility
  • aggregate head to head to form dimers
  • aggregate lateraly into sheet like structures
Term
Loction of Type IV collagen
Definition

basal lamina

Term
How are cross links formed between collagen molecules
Definition
  1. Lysine is oxidized to form allysine via lysyl oxidase, removing its NH3 from its R group
  2. When the R group of lysine and allysine come together, a water molecule is removed
  3. this forms a double bond between N and CH, forming a schiff base (lost water btw aldehyde and amine)
Term
Location of Type II collagen in body
Definition

cartilage

vitreous humnor

Term
Location of type III collagen
Definition
blood vessels
Term
Describe unique quarternary structure of type II collagen
Definition
short thin fibrils that are heavily glycosylated
Term
Functional advantage of cross linking between lysine and allysine
Definition

provides increasing tensile strength

Term
How is the supercoiled triple helix of procollagen formed?
Definition
the three alpha chains come together in the endoplasmic reticulum, they then turn into supercoiled helix
Term

Why does scurvy affect procollagen formation?

Definition
vitamin C is a cofactor that puts hydroxyl group on Proline, and the hydroxyproline is critical to stailize the supercoiled triple helix via hydrogen bonds with water
Term
Describe tertiary structure of collagen
Definition
No real tertiary structure (globular heads are removed, taking away tertiary structure)
Term

How does the collagen know to get glycosylated and when hydroxyl group added to lysine?

Definition
  • put sugar at same hydroxylysine and hydroxyl group based on the primary sequence
Term
Effect of glycosylation on collagen
Definition
  • sugar takes up a lot of space, and its chemical properties allow a lot of water is associated with the sugar (ex: diabetic urinating glucose and water follow glucose)
  • because water is packed along the sugar, it will not allow the collagen to pack, so the fibrils will be short, thin
Term
Cause of Ehrler Danlos syndrome
Definition
disruption of Gly-X-Y repeat by substituting for a Gly
Term
Bond that stabilizes secondary structure
Definition
H bonds between carboxy O and amino H of AA, NOT the side chain (side chain H bonds is tertiary)
Term
Role of Histadines in hydrophobic pocket of beta chains of hemoglobin
Definition
  • one histadine will coordinate to heme nitrogen in its imidazole ring
  • remember, ferrous can have six bonds (4 bond to pyrrole rings and one to the His)
  • another histadine sits above the plane of the ring, so it cant form coordination with ferrous
    • the position of these two histadines means histadine must bind to antigen
  • when oxygen come in, iron moves up into the plane of ring (relaxed subunit), so the proceeding oxygens come in easier
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