Hemoglobin and Insulin

Hemoglobin is composed of 4 globin molecules. 2 alpha globins 2 beta globins 4 Heme molecules

Structure of Hemoglobin

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Molecular structure of the heme,with the iron in its center.a porphyrin ring, which contains 4 pyrrole molecules cyclically linked together, and an iron ion ligand bound in the center

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Hemeproteins are a group of specialized proteins that contain heme as a tightly bound prosthetic group.

For example, the heme group of a cytochrome functions as an electron carrier that is alternately oxidized and reduced.

In contrast, the heme group of the enzyme catalase is part of the active site of the enzyme that catalyzes the breakdown of hydrogen peroxide.

hemoglobin and myoglobin, the two most abundant heme-proteins in humans, the heme group serves to reversibly bind oxygen.

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Structure of heme: Heme is a complex of protoporphyrin IX and ferrous iron.

The iron is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring.

The heme can form two additional bonds, one on each side of the planar porphyrin ring.

For example, in myoglobin and hemoglobin, one of these positions is coordinated to the side chain of a histidine residue of the globin molecule, whereas the other position is available to bind oxygen.

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The alpha globin chain is composed of 141 amino acids & the beta globin chain is composed of 146 amino acids

Both alpha and beta proteins share similar secondary and tertiary structures

Hemoglobin Structure

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Structure and function of hemoglobin

Hemoglobin is found exclusively in red blood cells, where its main function is to transport oxygen from the lungs to the capillaries of the tissues.

Hemoglobin A, the major hemoglobin in adults, is composed of four polypeptide chains.

Two alpha chains and two beta chains held together by noncovalent interactions.

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Quaternary structure of hemoglobin:

The hemoglobin tetramer can be envisioned as being composed of two identical dimers (αβ)1 and (αβ)2 in which the numbers refer to dimers one and two.

The two polypeptide chains within each dimer are held tightly together, primarily by hydrophobic interactions.

Hydrophobic amino acid residues are localized not only in the interior of the molecule, but also in a region on the surface of each subunit.

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Interchain hydrophobic interactions form strong associations between α-subunits and β subunits in the dimers.

Ionic and hydrogen bonds also occur between the members of the dimer.

In contrast, the two dimers are able to move with respect to each other, being held together primarily by polar bonds.

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Oxygen diffuses from alveolar air into the blood because the venous blood has a lower partial pressure.

The oxygen dissolves in the blood Small amount is carried as solution

0.31-ml per 100-ml The remainder of the oxygen is carried in

chemical composition with the hemoglobin in red blood cells

Oxygen Transport

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Normal hemoglobins in adults

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Each globin chain (not hemoglobin) is controlled by a separate gene. Genes are listed with the number inherited from each parent and the chromosome on which they lie. There are two different gamma genes (and chains) that differ by one amino acid - a matter of little clinical significance.The gamma, delta and beta genes lie next to each other on chromosome 11. The two alpha genes lie next to each other on chromosome 16.

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Insulin is a hormone central regulating carbohydrate and fat metabolism in the body.

Insulin causes liver cells, muscle cells and fat tissue to take up glucose from the blood and store it as glycogen in the liver and muscle.

Insulin

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Insulin is producted by the pancreas, which has two important functions :1. Producing hormones – insulin and glucagon which regulate blood sugar levels.2. Producing pancreatic digestive enzymes.

Insulin is released when any of the several stimuli are detected– stimuli include ingested protein and glucose in the blood from digested food.

Production of insulin

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Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of 5808 Da.

Insulin structure

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Insulin is produced and stored in the body as a hexamer , while the active form is the monomer.

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Mature insulin consists of the 21 amino acids in A chain

and 30 amino acids in B chain linked by disulfide bonds.

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Structure of Insulin

Insulin is synthesized as a preprohormone22

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Insulin Molecule

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Control of the cellural intake of certain substances.

Increase of DNA replication and protein sythesis.

Modification of the activity of numerous enzymes.

Actions of insulinon the human metabolism

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It stimulates synthesis of glycogen, fat, and protein.

It inhibits breakdown of glycogen, fat, and protein.

It increases glucose transport into cells.

It is the main hormone that controls the blood glucose level.

Actions of insulinon the human metabolism

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Insulin is being produced biosynthetically using recombinant DNA technology. More recently, reserchers have succeded in introducing the human insulin gene into plants and in producing insulin in them. This technique is set to reduce production costs.

Before it was possible to produce insulin biosynthetically it wa aquired from animals and purified so it could be used as injections.

Insulin for medical purposes

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Protein Denaturation

It results in the unfolding and disorganization of the protein's secondary and tertiary structures, which are not accompanied by hydrolysis of peptide bonds.

Denaturing agents include:heat, organic solvents, mechanical mixing, strong acids or bases, detergents, and ions of heavy metals such as lead and mercury.

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Denaturation may, under ideal conditions, be reversible, in which case the protein refolds into its original native structure when the denaturing agent is removed.

However, most proteins, once denatured, remain permanently disordered.

Denatured proteins are often insoluble and, therefore, precipitate from solution.

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