Respiratory Biochemistry Flashcards
Primary Structure
Sequence of amino acids by polypeptide bonding (N-terminus to C-terminus)
Secondary Structure
- Alpha-Helix (Side chains stick out and hydrogen bonding parallel)
- Beta-Sheet (Side chains stick in and out and hydrogen bonds form in “middle”)
Tertiary Structure
- Formed by a folding of a secondary structure on top of itself.
- Creation of a 3D structure (and protein shape)
Quaternary Structure
Two or more polypeptides coming together.
Globular Proteins
- Water soluble (hydrophilic) proteins and are therefore have polar side chains on surface.
- Nonpolar side chains are in the interior. Creation of “hydrophobic core”
Function of Globular Proteins
Catalysis, regulation, and transport within body.
How is the alpha helix stabilized?
By hydrogen bonds within the peptide chain.
How are tertiary structures stabilized?
1) By hydrogen bonding b/w amino acid side chains.
2) Disulfide bond formation (from two cysteine amino acids).
3) Ionic Interaction b/w two charged amino acids.
Function of hemoglobin
To transfer oxygen in body to tissue
Why is free oxygen dangerous in the body
B/c it is somewhat toxic b/c of oxidizing behavior.
What is heme (general)?
Heme is a prosthetic group (not a part of proteins structure). It binds to the globin (globular protein) in order to aid in the transfer of oxygen in the body.
Why is heme so important?
B/c oxygen is so toxic, the heme protects against the radioactive oxygen. Specifically, the ferrous ion minimizes the “dangerous” chemistry.
What is heme comprised of?
Porphyrin Ring + Ferrous iron (Fe 2+)
Describe porphyrin
Nitrogenous ringed structure
Cells that have heme containing proteins MUST also contain:
Mitochondria
Name two examples of globular hemeproteins:
1) Hemoglobin
2) Myoglobin
Where is myoglobin found?
In the muscle
Describe the structure of myoglobin
Made of ONE (a-helix) polypeptide chain (tertiary)
There is one heme group attached to this one subunit
Describe the structure of hemoglobin
Made of FOUR polypeptide chains (subunits).
Subunits:
1) a1 (with attached heme)
2) a2 (with attached heme)
3) b1 (with attached heme)
4) b2 (with attached heme)
FOUR subunits => TETRAMER
Each subunit will have a heme bound to it.
Specifically there are TWO DIMERS associated with hb. a1ba and a2b2
Describe the bonds found in hemoglobin
Dimers (a1b1 and a2b2) will have STRONG hydrophobic interactions with themselves separate.
However, both dimers will form a WEAK hydrogen bond and ionic bonds that keep both dimers attached to each other and form the tetramer.
Visualization: Double forearm technique.
How is heme bond to the globin (either in myoglobin and hemoglobin)
1) Histidine covalent bond to ferrous ion
2) Hydrophobic interactions
How many oxygens can be carried on myoglobin?
One
How many oxygens can be carried on Hemoglobin?
Four
What is the function of myoglobin
Store oxygen
Where is hemoglobin found
In blood
When hemoglobin is in the taut state we assume
low oxygen presence (wants to be giving off oxygen).
When hemoglobin is in the relaxed state we assume
high presence of oxygen (wants to be taking in oxygen)
Hydrophobic interaction between the dimers of hemoglobin will require what type of amino acids
Nonpolar amino acids
What amino acids have hydrophobic side chains
Vicken Told Loucine: "I Tried Pie" X X X XX X Made Alexia Punch Grandpa X X X X Valine Tyrosine Leucine Isoleucine Tryptophan Phenylalanine Methionine Alanine Proline Glycine
When O2 binds to heme what conformational change do we see
(Nonplanar => Planar)
(Taut=>Relaxed)
(Deoxygenated=> Oxygenated)
Describe the saturation curve of hemoglobin vs myoglobin.
Hemoglobin is sigmoidal
Myoglobin is hyperbolic
Myoglobin has a higher affinity (shifted left than hemoglobin)
See slide 45 of RESP. BIOCHEM
Explain the sigmoidal behavior of hemoglobin
COOPERATIVE LIGAND BINDING.
Affinity starts low but as o2 binds to hb, the hb gets very hungry and more binding ensues. A leveling off of affinity eventually happens.
Name 4 things that can affect hb affinity
1) pH
2) CO2
3) Body Temperature
4) 2-3 bisphosphoglycerate
Decrease of pH does what to hemoglobin
Decrease in pH causes the hemoglobin to be in a charged state.
Charged state => bond holding ab dimers to form tetramer got a whole lot stronger
This charged state => taut state.
Taut state means that hb has low affinity for O2 and wants to transport it to tissue.
Increase in pH does what to hemoglobin
Increase in pH causes the hemoglobin to be in an uncharged state (between the bond forming the tetramer)
Uncharged state => relaxation state.
Affinity of hemoglobin to o2 goes up and hemoglobin was to hold onto o2 rather than give it up to tissue.
Bohr Affect
The Bohr Effect refers to the observation that increases in the carbon dioxide partial pressure of blood or decreases in blood pH result in a lower affinity of hemoglobin for oxygen.
What is 2-3 bisphosphoglycerate
A substrate produced from a side reaction of glycolysis.
2-3 bpg is a highly negative charged substrate
Function of 2-3 bpg
Potent regulator of hb o2 affinity. If bound to charge hydrogen bonds and ionic bonds of hb tetramer, THIS drives taut state.
HIGH 2-3 BPG => TAUT STATE => Hb LOW AFFINITY TO O2 => RELEASE of O2 to tissue,
Relationship of hemoglobin to myoglobin
Hemoglobin transfers O2 to myoglobin. Myoglobin stores the o2 till the muscles need it (Myoglobin gives to mitochondria of cell)
Bonds that ferrous ion forms in Hb
Ferrous ion forms a total of 6 bonds:
4 bonds => porphyrin ring
1 bond => proximal histidine
1 bond => reversible oxygen binding
Differences between fibrous and globular proteins.
Fibrous:
- looks like rope
- structural
- hold a secondary structure
- stabilized by hydrogen bonds
- held by a parallel polypeptide bond
- insoluble in water
Globular:
- looks like globe
- tertiary or quaternary
- stabilized by disulfide bonds, ionic interactions, hydrogen bonds, metallic bonds, and hydrophobic interactions
- soluble in water
What amino acid acts as a good acid base buffer
Histidine
