-
Make up about 15% of the cell
Proteins
-
Functions of protein
[ESTCIHCS]
- enzymes
- structural
- transport & storage
- Cell signaling
- immune protection
- Hormones
- Coordinated Motion
- Special functions
-
catalytic activity (amylase, lipase, pepsin)
Enzyme
-
collagen, α-Keratin, fibroin, elastin
Structural
-
Hb, ambumin, Mb
Transport and storage
-
Membrane receptors (insulin receptors)
Cell Signaling
-
immunoglobulins
Immune protection
-
Insulin, Glucagon
hormones
-
actin & myosin
coordinated motion
-
determines function or activity of proteins
Shape or Conformation
-
proteins are made of AA linked by ________
Peptide Bond
-
Repeating sequence of the N-Cα-C-N-Cα-C-N-Cα-C in peptide bond
Polypeptide backbone
-
nor part of backbone or the peptide bond
side chain or R
-
Classification of Protein
-
composed only of amino acids
Simple Proteins
-
Example of Simple Proteins
- albumin
- histones
- protamines
-
Contains non-Protein Group (prosthetic group)
Conjugated Proteins
-
Example of conjugated proteins
[NGLMPC]
- nucleoproteins
- glycoproteins
- lipoproteins
- metalloproteins
- phosphoproteins
- chromoproteins
-
help determine the conformation in an aqueous solution
side chain
-
determined by the sequence of the amino acids
Protein shape
-
the final shape and has the lowest free energy possible
conformation
-
the process of unfolding the protein
denaturation
-
denaturing agents
- heat
- pH
- chemical compounds (alcohol, urea, acids and base)
-
2 regular folding patterns
-
proteins turns like a spiral-fibrous protein (hair, nails, horns)
α-Helix
-
proteins folds back on itself as in a ribbon-globular protein
β-sheet
-
core of many protein
β-sheet
-
form a rigid structure with H-bond
β-sheet
-
-
run in opposite direction of its neighbors
Anti-parallel
-
run in the same direction with longer looping sections between them
parallel
-
formed by H-bond between every 4th peptide bond -C=O to N-H
α-Helix
-
Usually in proteins that span a membrane (membrane proteins)
α-Helix
-
can coil to the right or left and around each other
α-Helix
-
a framework for structural proteins such as the hair, nails and skin
coiled-coil shape
-
types of protein shape
- Globular Proteins
- Fibrous Proteins
-
soluble in water, compact shape like a ball with irregular surfaces
globular proteins
-
2° structure is a mixture of α, β & loop structures
globular proteins
-
example of globular proteins
ETIHM
- Enzyme
- Transport proteins
- immunoglobulins
- hormones
- myoglobin
-
usually span a long distance in the cell
Fibrous Protein
-
3D structure is usually long and rod shaped, insoluble in water, structural function
Collagen, Keratin, Silk fibroin, elastin
-
a right handed alpha helix
Alpha Keratin
-
composed of a pair of coiled-coil
Protofilament
-
composed of 2 pairs of protofilaments or a microfilament
Protofibrils
-
composed of about four protofibrils or about 32 strands of α-keratin
Intermediate Filament/ Microfibril
-
an array of many α-keratin filaments
strand of hair
-
the key structural material making up the outer layer of human skin, and also a key structural component of hair and nails
Keratin
-
basic structural unit of alpha keratin
alpha helix
-
found in horns and nails have more disulfide bonds
Hard Keratins
-
found in wools, hair and feather
soft keratin
-
Most abundant protein in the human body (25% of total protein weight of human body)
collagen
-
insoluble fibers that have high tensile strength
Collagen
-
consist of 3 α-chains of same size tightly wrapped around each other
Collagen
-
major structural material in tendons, cartilage, ligaments, blood vessels and skin, eye cornea, organic component of bone and teeth
Collagen
-
predominant structural features in collagen
Triple helix
-
a left handed with 3 AA residues per turn
collagen alpha chain
-
required at the tight junction where the 3 helices meet
Glycine
-
together with keratin, is responsible for skin strength and elasticity
Collagen Triple Helix
-
produces a bend in the polypeptide chain, responsible for 2° structure of collagen
Proline
-
every 3rd 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
1° structure
-
beeding of gums, skin discoloration result from fragile collagen due to Vit C deficiency
Scurvy
-
are made up of collagen molecules aligned in a staggered fashion and cross-linked for strength
Collagen fibrils
-
abnormal bone formation in babies, Bones easily bend and fracture
osteogenesis imperfecta/ Brittle bone Syndrome
-
characterized by stretchy skin and loose joints
Ehlers-Danlos syndrome
-
deficiency in Ascorbic acid needed for hydroxylation of pro and lys, resulting collagen has decreased tensile strength
Scurvy
-
major protein component of tissues that require elasticity such as arteries, lungs, bladder, skin, and elastic ligaments and cartilages
elastin
-
composed of soluble tropoelastin protein containing primarily glycine and val and modified alanine and proline residues
elastin
-
a 65kDa protein that is highly cross-linked to form an insoluble complex
tropoelastin
-
with rubber-like properties, structure is irregular or a random coil
elastin
-
can be stretched to several times its normal length but recoil to its original shape when stretching force is relaxed
elastin
-
involves in cross-linking if elastin
lysine
-
the protein in silk, produced by insects and spiders
Fibroin
-
does not stretch bec it is already extended but it is flexible
silk
-
causes a total or partial loss of biological activity, loss of structure and function
denaturation
-
specific 3D conformation is changed by breaking some bonds without breaking its primary structure
denaturation
-
disruption of weak forces that stabilize proteins
denaturation
-
precipitation out of biochemical solutions of denatured proteins
coagulation
-
denatured completely by urea in the presence of a reducing agent
ribonuclease A
-
a hemoprotein only found in the cytoplasm of erythrocyte (RBC)
hemoglobin
-
transports O2 and CO2 bet lungs and various tissues
hemoglobin
-
Buffer a lot of Histidine
hemoglobin
-
a tetramer (2α & 2β)
hemoglobin
-
Binds O2 reversibly like Mb But binding is cooperative
hemoglobin
-
both α & β chains are strikingly similar to that of Mb
hemoglobin
-
normal concentration of Hb in blood
- males 135 - 175 g/L
- female 120-168 g/L
-
predominant structure of Mb and Hb
α-helix
-
each globin contains:
1 heme group with a central Fe2+ ion
-
Heme structure
metalloporphyrine (cyclic tetrapyrrole)
-
heme contains
- conjugated system of double bonds
- photoporphyrine ring
- 1 iron cation
-
bound in the middle of tetrapyrrole skeleton by 4 coordination covalent bond
iron cation
-
coordination number of iron in heme
6
-
6 bonds of iron in heme
- 4N of 4 pyrrole rings
- link to His F8
- link to an O2
-
reduces ferric acid to ferous
Ascorbic acid
-
Hemoproteins
- hemoglobin
- myoglobin
- cytochromes
- catalases
- peroxidases
-
hemoproteins that binds O2
-
hemoproteins which is found in electron transport chain
cytochromes
-
hemoproteins which is an enzyme
-
the 5th coordination bond of Fe is formed with
His F8 (proximal)
-
the 6th bond is for O2 is formed with
His E7 (Distal)
-
which has stronger affinity
Mb
-
a single chain globular protein of 153 AA, containing 1 Heme group
Mb
-
transports oxygen in skeletal and heart muscles
Mb
-
found in cytosol within cells and marker of myocardial damage
Mb
-
stores oxygen in red muscle cell
Mb
-
2α and 2β subunits
Adult Hb (Hb A)
-
Minor form of Hb in adults. it forms only 2-3% of a total Hb A (2α, 2δ)
HbA2
-
the major form of Hb in adults and in children over 7 months
HbA1
-
2α, 2γ subunits, in fetus and newborn infants Hb binds O2 at lower tension than Hb A
Fetal Hb (Hb F)
-
has a higher affinity to oxygen
Hb F
-
in the β-globulin chain Glu is replaced by Val (6th AA), an abnormal Hb typical for sickle cell anemia
Hb S
-
Oxygen Dissociation curve of Mb
Hyperbolic
-
Oxygen dissociation curve of Hb
Sigmoidal
-
higher affinity to oxygen shifts to
left
-
lower affinity to oxygen shifts to
right
-
at tissue ___ of Hb's O2 has been unloaded
50%
-
at tissue ___ of Mb's O2 remains
95%
-
Derivatives of Hemoglobin
[ODMCCG]
- Oxyhemoglobin (oxyHb)
- Deoxyhemoglobin (deoxyHb)
- Methemoglobin (metHb)
- Carbonylhemoglobin (HbCO)
- Carbaminohemoglobin (HbNHCO2-)
- Glycatedhemoglobin (HbA1c)
-
Hb with O2
Oxyhemoglobin (oxyHb)
-
Hb without O2
Deoxyhemoglobin (deoxyHb)
-
contains Fe3+ instead of Fe2+ in heme groups
Methemoglobin (metHb)
-
-CO bind with Fe2+ in heme in case of CO poisoning or smoking
Carbonylhemoglobin (HbCO)
-
200x higher affinity to Fe2+ than O2
Carbon Monoxide (CO)
-
-CO2 is bound to the N-Terminal amino group of the T form of Hb, it transports CO2 in blood
Carbaminohemoglobin (HbNHCO2-) Carbamate
-
formed spontaneously by nonenzymatic reaction with Glc, high in diabetic patients
Glycatedhemoglobin (HbA1c)
-
-
HbA1c reflects mean blood glucose concentration over ________
6-8 wks
-
Provides valuable information for management of Diabetes mellitus
HbA1c
-
binds 4 molecules of O2 per tetramer, 1 per heme
Hemoglobin
-
Hemoglobin features/ characteristics
- cooperative binding
- transports H+ and CO2
- Allosteric Protein
- Binds 4 O2
- tetramer
- Bhor effect
- Affinity for O2 dependent on pH
- Lower O2 affinity
-
Myoglobin features/ characteristics
- transports O2 only
- not Allosteric Protein
- Binds one O2
- heme/ monomer
- not dependent on pH
- higher O2 affinity
-
Active metabolism in Tissue:
- ↑ H+
- ↑ CO2
- ↓ O2
- ↓ pH
- ↑ 2,3-BPG
-
Active metabolism in lungs:
- ↓ H+
- ↓ CO2
- ↑ O2
- ↑pH
- no 2,3-BPG
-
2 ways CO2 can be transported
- carbamate (15% in venous blood)
- Bicarbonate (CO2 + H2O > carbonic acid > HCO3- + H+)
-
byproduct of respiration, is transported by hemoglobin from peripheral tissues to the lungs
CO2
-
a buffer in erythrocytes
Hb
-
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
Bohr effect
-
2 different forms of Hb
- T-form (tense)
- R-form (relaxed)
-
the deoxygenated form, has low O2 affinity, bound with 2,3-BPG, favored by interactions
T-form
-
oxygenated form, High O2 affinity, with bound O2
R-form
-
enhances the release of oxygen to tissues
Low pH (High H+)
-
increase H+ promoting the unloading of Oxygen to tissues
High pCO2
-
promotes unloading of oxygen because it stabilizes the T conformation
2,3-BPG
-
effect of increasing BPG concentration
O2 Dissociation curve shifts to the right (dec in O2 affinity)
-
When BPG is absent
O2 Dissociation curve shifts to the left (inc in O2 affinity)
-
when pH is decreased
ODC shifts to the right
-
when pH is increased
ODC shifts to the left
-
binding of H+ by Hb (lower pH)
lowers its affinity for O2
-
high CO2 levels in the plasma result in a
ODC shifts to the right
-
ATP is generated by
anaerobic glycolysis
-
used for ion transport across the cell membrane
ATP
-
produces 2,3 BPG and lactate
glycolysis
-
Disorders caused by production of structurally abnormal Hb
HEMOGLOBINOPATHIES
-
example of HEMOGLOBINOPATHIES
- Sickle-cell anemia
- thalassemias
-
a homozygous recessive disorder, inherited from two mutant genes from each parent
Sickle-cell anemia
-
sickle cell anemia is characterized by
- hemolytic anemia
- susceptibility to infection
-
Sickle cell trait
- have one normal and one mutant gene
- heterozygous
- RBC contains both HbS and HbA
- Do not display clinical symptoms and live normal lives
-
provide protection against malaria parasite Plasmodium falciparum which spends a part of its life cycle in the RBC
Heterozygous state
-
Sickle cell trait is prevalent among
black americans/ african countries
-
Defective biosynthesis of globin chain, genetic defects of hemolytic anemias
Thalassemias
-
inherited autosomal recessive blood diseases
Thalassemias
-
are prevalent in population where malaria was endemic - arab americans, people of mediterranean origins and asians
Thalassemias
-
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
Thalassemias
-
due to trauma or massive crash injury myoglobin is released from damaged muscle fiber, Urine becomes dark red
myoglobinuria
-
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)
anemia
|
|