PROTEINS

Make up about 15% of the cell

Functions of protein

catalytic activity (amylase, lipase, pepsin)

collagen, α-Keratin, fibroin, elastin

Hb, ambumin, Mb

Membrane receptors (insulin receptors)

immunoglobulins

Insulin, Glucagon

actin & myosin

determines function or activity of proteins

proteins are made of AA linked by ________

Repeating sequence of the N-C_α-C-N-Cα-C-N-Cα-C in peptide bond

nor part of backbone or the peptide bond

Classification of Protein

composed only of amino acids

Example of Simple Proteins

Contains non-Protein Group (prosthetic group)

Example of conjugated proteins

help determine the conformation in an aqueous solution

determined by the sequence of the amino acids

the final shape and has the lowest free energy possible

the process of unfolding the protein

denaturing agents

2 regular folding patterns

proteins turns like a spiral-fibrous protein (hair, nails, horns)

proteins folds back on itself as in a ribbon-globular protein

core of many protein

form a rigid structure with H-bond

2 types of β-sheet

run in opposite direction of its neighbors

run in the same direction with longer looping sections between them

formed by H-bond between every 4^th peptide bond -C=O to N-H

Usually in proteins that span  a membrane (membrane proteins)

can coil to the right or left and around each other

a framework for structural proteins such as the hair, nails and skin

types of protein shape

soluble in water, compact shape like a ball with irregular surfaces

2° structure is a mixture of α, β & loop structures

example of globular proteins

usually span a long distance in the cell

3D structure is usually long and rod shaped, insoluble in water, structural function

a right handed alpha helix

composed of a pair of coiled-coil

composed of 2 pairs of protofilaments or a microfilament

composed of about four protofibrils or about 32 strands of α-keratin

an array of many α-keratin filaments

the key structural material making up the outer layer of human skin, and also a  key structural component of hair and nails

basic structural unit of alpha keratin

found in horns and nails have more disulfide bonds

found in wools, hair and feather

Most abundant protein in the human body (25% of total protein weight of human body)

insoluble fibers that have high tensile strength

consist of 3 α-chains of same size tightly wrapped around each other

major structural material in tendons, cartilage, ligaments, blood vessels and skin, eye cornea, organic component of bone and teeth

predominant structural features in collagen

a left handed with 3 AA residues per turn

required at the tight junction where the 3 helices meet

together with keratin,  is responsible for skin strength and elasticity

produces a bend in the polypeptide chain, responsible for 2° structure of collagen

every 3^rd AA is gly which bec of its small side chain is the only AA that can fit into the restricted space where the 3 heices meet

beeding of gums, skin discoloration result from fragile collagen due to Vit C deficiency

are made up of collagen molecules aligned in a staggered fashion and cross-linked for strength

abnormal bone formation in babies, Bones easily bend and fracture

characterized by stretchy skin and loose joints

deficiency in Ascorbic acid needed for hydroxylation of pro and lys, resulting collagen has decreased tensile strength

major protein component of tissues that require elasticity such as arteries, lungs, bladder, skin, and elastic ligaments and cartilages

composed of soluble tropoelastin protein containing primarily glycine and val and modified alanine and proline residues

a 65kDa protein that is highly cross-linked to form an insoluble complex

with rubber-like properties, structure is irregular or a random coil

can be stretched to several times its normal length but recoil to its original shape when stretching force is relaxed

involves in cross-linking if elastin

the protein in silk, produced by insects and spiders

does not stretch bec it is already extended but it is flexible

causes a total or partial loss of biological activity, loss of structure and function

specific 3D conformation is changed by breaking some bonds without breaking its primary structure

disruption of weak forces that stabilize proteins

precipitation out of biochemical solutions of denatured proteins

denatured completely by urea in the presence of a reducing agent

a hemoprotein only found in the cytoplasm of erythrocyte (RBC)

transports O₂ and CO₂ bet lungs and various tissues

Buffer a lot of Histidine

a tetramer (2α & 2β)

Binds O₂ reversibly like Mb But binding is cooperative

both α & β chains are strikingly similar to that of Mb

normal concentration of Hb in blood

predominant structure of Mb and Hb

each globin contains:

Heme structure

heme contains

bound in the middle of tetrapyrrole skeleton by 4 coordination covalent bond

coordination number of iron in heme

6 bonds of iron in heme

reduces ferric acid to ferous

Hemoproteins

hemoproteins that binds O₂

hemoproteins which is found in electron transport chain

hemoproteins which is an enzyme

the 5th coordination bond of Fe is formed with

the 6th bond is for O₂ is formed with

which has stronger affinity

a single chain globular protein of 153 AA, containing 1 Heme group

transports oxygen in skeletal and heart muscles

found in cytosol within cells and marker of myocardial damage

stores oxygen in red muscle cell

2α and 2β subunits

Minor form of Hb in adults. it forms only 2-3% of a total Hb A (2α, 2δ)

the major form of Hb in adults and in children over 7 months

2α, 2γ subunits, in fetus and newborn infants Hb binds O₂ at lower tension than Hb A

has a higher affinity to oxygen

in the β-globulin chain Glu is replaced by Val (6^th AA), an abnormal Hb typical for sickle cell anemia

Oxygen Dissociation curve of Mb

Oxygen dissociation curve of Hb

higher affinity to oxygen shifts to

lower affinity to oxygen shifts to

at tissue ___ of Hb's O₂ has been unloaded

at tissue ___ of Mb's O₂ remains

Derivatives of Hemoglobin

Hb with O₂

Hb without O₂

contains Fe³⁺ instead of Fe²⁺ in heme groups

-CO bind with Fe²⁺ in heme in case of CO poisoning or smoking

200x higher affinity to Fe²⁺ than O₂

-CO₂ is bound to the N-Terminal amino group of the T form of Hb, it transports CO₂ in blood

formed spontaneously by nonenzymatic reaction with Glc, high in diabetic patients

half life of RBC

HbA1c  reflects mean blood glucose concentration over ________

Provides valuable information for management of Diabetes mellitus

binds 4 molecules of O₂ per tetramer, 1 per heme

Hemoglobin features/ characteristics

Myoglobin features/ characteristics

Active metabolism in Tissue:

Active metabolism in lungs:

2 ways CO₂ can be transported

byproduct of respiration, is transported by hemoglobin from peripheral tissues to the lungs

a buffer in erythrocytes

High H⁺ and high CO₂ (low pH) promotes the release of O2 to tissues and High O₂ will promote the release of H⁺ and CO₂ in the lungs

2 different forms of Hb

the deoxygenated form, has low O₂ affinity, bound with 2,3-BPG, favored by interactions

oxygenated form, High O₂ affinity,  with bound O₂ 

enhances the  release of oxygen to tissues

increase H⁺ promoting the unloading of Oxygen to tissues

promotes unloading of oxygen because it stabilizes the T conformation

effect of increasing BPG concentration

When BPG is absent

when pH is decreased

when pH is increased

binding of H⁺ by Hb (lower pH)

high CO₂ levels in the plasma result in a

ATP is generated by

used for ion transport across the cell membrane

produces 2,3 BPG and lactate

Disorders caused by production of structurally abnormal Hb

example of HEMOGLOBINOPATHIES

a homozygous recessive disorder, inherited from two mutant genes from each parent

sickle cell anemia is characterized by

Sickle cell trait

provide protection against malaria parasite Plasmodium falciparum which spends a part of its life cycle in the RBC

Sickle cell trait is prevalent among

Defective biosynthesis of globin chain, genetic defects of hemolytic anemias

inherited autosomal recessive blood diseases

are prevalent in population where malaria was endemic - arab americans, people of mediterranean origins and asians

genetic defects result in reduced rate of synthesis of alpha and beta globin chain - it causes the formation of abnormal Hb molecule results to anemia

due to trauma or massive crash injury myoglobin is released from damaged muscle fiber, Urine becomes dark red

reduction in number or RBC and decrease Hb in  the blood, impaired synthesis of hemoglobin (Fe deficiency) and production of erythrocytes (folic acid, Vit B. deficiency)