Respiratory Biochemistry

Question 1

Primary Structure

Answer 1

Sequence of amino acids by polypeptide bonding (N-terminus to C-terminus)

Question 2

Secondary Structure

Answer 2

• Alpha-Helix (Side chains stick out and hydrogen bonding parallel)
• Beta-Sheet (Side chains stick in and out and hydrogen bonds form in “middle”)

Question 3

Tertiary Structure

Answer 3

• Formed by a folding of a secondary structure on top of itself.
• Creation of a 3D structure (and protein shape)

Question 4

Quaternary Structure

Answer 4

Two or more polypeptides coming together.

Question 5

Globular Proteins

Answer 5

• Water soluble (hydrophilic) proteins and are therefore have polar side chains on surface.
• Nonpolar side chains are in the interior. Creation of “hydrophobic core”

Question 6

Function of Globular Proteins

Answer 6

Catalysis, regulation, and transport within body.

Question 7

How is the alpha helix stabilized?

Answer 7

By hydrogen bonds within the peptide chain.

Question 8

How are tertiary structures stabilized?

Answer 8

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.

Question 9

Function of hemoglobin

Answer 9

To transfer oxygen in body to tissue

Question 10

Why is free oxygen dangerous in the body

Answer 10

B/c it is somewhat toxic b/c of oxidizing behavior.

Question 11

What is heme (general)?

Answer 11

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.

Question 12

Why is heme so important?

Answer 12

B/c oxygen is so toxic, the heme protects against the radioactive oxygen. Specifically, the ferrous ion minimizes the “dangerous” chemistry.

Question 13

What is heme comprised of?

Answer 13

Porphyrin Ring + Ferrous iron (Fe 2+)

Question 14

Describe porphyrin

Answer 14

Nitrogenous ringed structure

Question 15

Cells that have heme containing proteins MUST also contain:

Answer 15

Mitochondria

Question 16

Name two examples of globular hemeproteins:

Answer 16

1) Hemoglobin

2) Myoglobin

Question 17

Where is myoglobin found?

Answer 17

In the muscle

Question 18

Describe the structure of myoglobin

Answer 18

Made of ONE (a-helix) polypeptide chain (tertiary)

There is one heme group attached to this one subunit

Question 19

Describe the structure of hemoglobin

Answer 19

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

Question 20

Describe the bonds found in hemoglobin

Answer 20

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.

Question 21

How is heme bond to the globin (either in myoglobin and hemoglobin)

Answer 21

1) Histidine covalent bond to ferrous ion

2) Hydrophobic interactions

Question 22

How many oxygens can be carried on myoglobin?

Answer 22

One

Question 23

How many oxygens can be carried on Hemoglobin?

Answer 23

Four

Question 24

What is the function of myoglobin

Answer 24

Store oxygen

Question 25

Where is hemoglobin found

Answer 25

In blood

Question 26

When hemoglobin is in the taut state we assume

Answer 26

low oxygen presence (wants to be giving off oxygen).

Question 27

When hemoglobin is in the relaxed state we assume

Answer 27

high presence of oxygen (wants to be taking in oxygen)

Question 28

Hydrophobic interaction between the dimers of hemoglobin will require what type of amino acids

Answer 28

Nonpolar amino acids

Question 29

What amino acids have hydrophobic side chains

Answer 29

``` 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 ```

Question 30

When O2 binds to heme what conformational change do we see

Answer 30

(Nonplanar => Planar) (Taut=>Relaxed) (Deoxygenated=> Oxygenated)

Question 31

Describe the saturation curve of hemoglobin vs myoglobin.

Answer 31

Hemoglobin is sigmoidal Myoglobin is hyperbolic Myoglobin has a higher affinity (shifted left than hemoglobin) See slide 45 of RESP. BIOCHEM

Question 32

Explain the sigmoidal behavior of hemoglobin

Answer 32

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.

Question 33

Name 4 things that can affect hb affinity

Answer 33

1) pH 2) CO2 3) Body Temperature 4) 2-3 bisphosphoglycerate

Question 34

Decrease of pH does what to hemoglobin

Answer 34

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.

Question 35

Increase in pH does what to hemoglobin

Answer 35

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.

Question 36

Bohr Affect

Answer 36

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.

Question 37

What is 2-3 bisphosphoglycerate

Answer 37

A substrate produced from a side reaction of glycolysis. 2-3 bpg is a highly negative charged substrate

Question 38

Function of 2-3 bpg

Answer 38

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,

Question 39

Relationship of hemoglobin to myoglobin

Answer 39

Hemoglobin transfers O2 to myoglobin. Myoglobin stores the o2 till the muscles need it (Myoglobin gives to mitochondria of cell)

Question 40

Bonds that ferrous ion forms in Hb

Answer 40

Ferrous ion forms a total of 6 bonds: 4 bonds => porphyrin ring 1 bond => proximal histidine 1 bond => reversible oxygen binding

Question 41

Differences between fibrous and globular proteins.

Answer 41

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

Question 42

What amino acid acts as a good acid base buffer

Answer 42

Histidine