Bahaa Najjar

Omar Sami

18

Mamoun ahram

1 | P a g e

In this sheet, we will continue talking about fibrous proteins & specifically about Keratin,

and then we will start discussing Globular proteins.

Fasten your seatbelts; here we go!

keratins : is an example of fibrous proteins, and it is composed of one type of

secondary structure which is -Helix; Right handed molecule.

Keratin has two types:

1- Alpha keratin found in mammals like humans.

2- Beta keratin found in birds and Reptiles الزواحف() .

1- Alpha keratin: it is a helical protein like elastin and collagen but alpha keratin has

unusual content of cysteine which means a lot of disulfide bonds.

We can find alpha keratin in nails and hair for example.

→→ What if we took a piece of hair & zoom in:

-One hair is composed of hundreds of macrofibrils.

-A Macrofibril is composed of hundreds of microfibrils.

- Each microfibril is composed of 8 protofibrils.

- A Protofibril is composed of two dimmers.

- A Dimer is a two chain structure; each one called protofilament.

“You can refer to the slides to visualize the picture”

Q) Why nails are harder than hair, although both of them contain alpha keratin?

Well, this also leads us to a further classification, while all keratin contains

disulfide bridges, yet some structures contain disulfide bridges more than other

the structures, which indicates that we have more disulfide bridges on nails,

Depending on the cysteine content:

a- Soft keratin.

b- Hard keratin.

2 | P a g e

- Hair Treatment:

First, let us study the effect of both cold and hot water on our hair:

Both Cold & Hot water tend to make hydrogen bonding with the Keratin protein;

weakening the already existed hydrogen bonds, so the hair falls down.

However, the high temperature of Hot water results in further weakening of hydrogen

bonding.

Note that: covalent Bonds such as disulfide bond, is not affected by heat.

Remember: Keratin has both Hydrogen bonding & Disulfide bonds.

Q) How can we change the “External” structure of the hair?

A) We should know that hair structure is affected GENETICALLY and any new hair will

have the old structure no matter the treatment.

To change the structure of the hair, we have to follow these steps:

Reduce the Disulfide Bonds → بدك ما زي شعرك بتمشطي/بتمشط → Re-Oxidize the disulfide

bonds to maintain the new shape.

We use “Thioglycolate” to rupture the Disulfide bonds.

We use “Hydrogen Peroxide” to Re-Oxidize the disulfide bonds.

Globular Proteins

There are two subtypes of globular proteins: All globular proteins are composed of one type of secondary structure; however, Hemoglobin & Myoglobin are composed of only one type of secondary structure, which is the “Alpha Helix”

3 | P a g e

• Both hemoglobin and Myoglobin contain a “Heme group”; So they can be

classified as Hemoproteins.

• They are the most clinically relevant proteins.

• Their main function is to bind to exogenous material; such as oxygen.

Hemoproteins: Hemoproteins may act as: 1- Binding Proteins: like Hemoglobin & Myoglobin. 2- Enzymes: Catalase enzyme; which is important in our bodies. 3- Electron transfer: which means that electrons may be transferred throughout

this protein; but why? Well, all of us know that the Heme group contains Iron, and Iron can switch between two oxidizing states, either: a- The reduced form “Ferrous” Fe+2 b- The oxidized form “Ferric” Fe+3

So it facilitates the movement of the electrons. ** Any Protein that contains a Heme Group and is responsible for the movement of electrons is called → Cytochrome. But wait! What is Heme? Heme is a non-proteinous material (a non-protein group covalently attached to a protein)., macro-cyclic structure, Organic in nature, and has Iron in the middle.

Heme is a flat molecule that has four cyclic groups known as pyrrole rings → These four rings form a large ring called Porphyrin.

4 | P a g e

We have different kinds of Heme’s, which differ in the Amino acid attachment to the Porphyrin ring. The most common Heme is (Heme B). Porphyrin ring + Fe → Heme. Porphyrin ring +Mg→ Chlorophyll. Porphyrin ring + Cobalt→ B12 ring; Cobalamin.

Iron: -Iron can bind in the center of the four rings.

-Fe is in the ferrous state (Fe+2) can form 6 bonds, as follow:

- 4 with the nitrogen of the rings.

- One, known as the fifth coordinate, with the nitrogen of the imidazole of Histidine,

known as proximal Histidine.

- One with O2, the sixth coordinate

→ Oxidation of iron to the Fe+3, ferric, state makes the molecule incapable of normal O2 binding. →Heme outside the protein is called free Heme; four Coordinated Heme.

-Upon absorption of light, Heme gives a deep red color. Remember that Iron should be in reduced form; ferrous state "Fe2+. Because the affinity of Oxygen is too low when the iron is in the oxidized form.

Structure of Myoglobin:

Myoglobin: is a tertiary structure 8 α-helices, designated A through H that are

connected by short non-helical regions.

5 | P a g e

It can be presented on two forms: a-Oxymyoglobin (oxygen-bound). b-Deoxymyoglobin (oxygen-free). Heme is found in middle.

• You should know that Myoglobin has a hydrophobic pocket in which the Heme

group is localized. → the hydrophobic pocket helps in keeping the iron in the reduced form. When we visualize the Heme group, we can notice that it is a five coordinated Heme & the sixth position has a Histidine not that close called, Distal Histidine. This Histidine is trying to prevent Oxygen from being too tightly bounded to Carbon; to allow an easy release of Oxygen to serve the main function of Myoglobin. Because best binding occurs when the two involved atoms are at 90 degrees angle, distal histidine tries to increase this angle to allow the oxygen to be loosely bounded to carbon→ matches the function. The distal histidine also acts as a gate that opens and closes as O2 enters the hydrophobic pocket to bind to the Heme. The Distal Histidine stabilizes the binding as it makes hydrogen bonds after the O2/CO/CN is bounded.

6 | P a g e

Remember that: The Heme group stabilizes the tertiary structure of Myoglobin.

-Another significance of distal histidine

Remember that:

-The planar heme group fits into a hydrophobic pocket of the protein and the myoglobin-heme interaction is stabilized by hydrophobic attractions.

-The hydrophobic interior of myoglobin (or hemoglobin) prevents the oxidation of iron, and so when O2 is released, the iron remains in the Fe(II) state and can bind another O2.

Oxygen binding to Myoglobin:

- Myoglobin binds O2 with high affinity.

- The P50, oxygen partial pressure required for 50% saturation of all Myoglobin molecules is 2.8 torrs or mm Hg only! Which is a very low pressure.

Proximal

histidine,Covalently

attach Distal histidine

#Carbon monoxide is higher

affinity to heme than oxygen

7 | P a g e

- Physiological Relevance: Given that O2 pressure in tissues is normally 20 mm Hg, meaning that Myoglobin is almost fully saturated with oxygen at normal

conditions.

- We need very small change in the X-axis to have a high change in the Y-axis; Hyperbolic Graph.

Hemoglobin:

Hemoglobin is a tetramer with 2 alpha and 2 beta subunits.

-The α and β chains contain multiple α-helices, α chain contains 7 α-helices and β chain contains 8 α-helices (similar to Myoglobin).

The binding of O2 to Myoglobin

saturation curve. hyperbolicfollows a

# Each one of alpha or beta subunit

Contains " heme "

Subunits interaction: 1-The chains interact with each other via hydrophobic interactions; therefore, hydrophobic amino acids are not only present in the interior of the protein chains, but also on the surface

2-Electrostatic interactions (salt bridges) and hydrogen bonds also exist between the two different chains.

8 | P a g e

Oxygen binding to hemoglobin:

Notice that: the Hemoglobin curve is called Sigmoidal curve; resembling the S letter.

-We need relatively high pressure to achieve oxygen saturation to Hemoglobin.

-Then, it releases oxygen and become unsaturated in tissues where the oxygen pressure is low (about 20 mm Hg).

Oxygen binds with hemoglobin with high affinity in lungs, and low

affinity in tissue.

Looking at the graph below, we can notice that we have a Plateau at the beginning of

the Hemoglobin curve, which means that though we increase pressure; yet the fractional

saturation is almost zero, until we reach pressure of almost 10 mmHg, then we start

noticing a difference. →→ This is due to the structure of Hemoglobin, when the first

Oxygen molecule binds to the first subunit; it makes it easier for the rest of the Oxygen

molecules to bind.

Love Is Wise … Hatred Is Foolish