m2l3 - fibrous and globular proteins

glycine residue

(collagen structure) every 3rd amino acid residue is a ____ residue

Triple helix

 Has 3.3 residues per turn and a rise per residue nearly twice that of an a-helix

 Every 3rd amino acid residue is a glycine residue

 Gly-Pro-X or Gly-Hyp-X

collagen structure

translation

synonym of protein synthesis

hydroxylation

addition of OH

1. Synthesis of a chains of pre-procollagen on

   ribosomes. A signal protein directs them to the

   RER

2. Cleavage of signal protein forms procollagen

3. Hydroxylation of lysine and proline

4. Glycosylation

biosynthesis of collagen

transferase

transfer of groups

Glycosylation

Addition of galactose and glucose to some hydroxylysine residues.

Glycosylation

The enzymes galactosyl transferase and glycosyl transferase are required for this process

Assembly of three a - chains to form procollagen

This involves the formation of disulfide bonds between parts of the polypeptide chains known as registration peptides, which occur at both ends of the pre-procollagen

tropocollagen

The resulting molecule is called______

Ehlers-Danlos Syndrome

Characterized by stretchy skin and loose joints;

Due to defect in genes that encode a-collagen-1, procollagen N-peptidase, or lysyl hydroxylase.

Osteogenesis imperfecta

 Brittle bone syndrome

 Bones easily bend and fracture

Menke’s Syndrome

Characterized by kinky hair and growth retardation

Menke’s Syndrome

is a genetic disorder caused by a mutation usually primarily in the Y Chromosome (boys) it affects the copper levels and metabolism in the body causing seizures, brain damage, weakened bones and muscles, organ shutdown and failure to thrive

Menke’s Syndrome

Due to dietary deficiency of copper required by lysyl oxidase, which catalyzes a key step in the formation of the covalent cross-links that strengthen collagen fibers

Scurvy

Best known defect in collagen biosynthesis

Scurvy

Deficiency of Vit.C (required by prolyl and lysyl hydroxylases)

Scurvy

Bleeding gums, swelling joints, poor wound healing, and ultimately death

Elastin

Connective tissue protein with rubber-like properties

Elastin

Found in lungs, walls of large blood vessels, and elastic ligaments

Elastin

Can be stretched to several time their normal length, but recoil to their original shape when relaxed

ELASTIN

Composed primarily of small non polar amino acid residues (e.g. G, A, V)

ELASTIN

Also rich in proline and lysine, but contains little hydroxyproline and hydroxylysine.

◼ Interchain cross-links form desmosine residues

DESMOSINE CROSS-LINK

An extensively interconnected, rubbery network that can stretch and bend in any direction when stressed, giving connective tissue elasticity

reactive oxygen species

ROS

neutrophil elastase

cleans mop

a-1 antitrypsin

inhibit neutrophil elastase (protease that degrades elastin of alveolar walls) - in elastin degration

EMPHYSEMA

Deficiency of -1 antitrypsin leads to destruction of the alveolar walls of the lungs resulting to _____

Administration of -1 AT

Treatment of EMPHYSEMA

Elastase

the lungs natural defense against the irritants

antitrypsin

Once the lungs has been cleaned, ______ deactivates elastase

antitrypsin

Without this enzyme, the elastase continues to consume anything in its path, including healthy lung tissue

a- KERATIN

Proteins that forms tough fibers;

◼ Found in the hair, nails, and outer epidermal layers of mammals;

◼ Constituents of intermediate filaments of cytoskeleton in certain cells.

GLOBULAR HEMEPROTEINS

Group of specialized protein that contains heme

GLOBULAR HEMEPROTEINS

Maintain a supply of oxygen essential for oxidative metabolism

– MYOGLOBIN

– HEMOGLOBIN

HEME

Fe+2- protoporphyrin IX

HEME

A cyclic tetrapyrrole

A planar network of conjugate double bonds absorbs visible light and colors heme deep RED

MYOGLOBIN (Mb)

A monomeric protein (153 amino acid residues) of the red muscles

MYOGLOBIN (Mb)

Used in some tissues, notably muscle,

– as a storage reserve of O2 and

– for intracellular transport of O2

Myoglobin Structure

◼ 78%  helical (the other 22% in

 turns and short loops, no  sheet at all)

◼ 8  - helices and connections between helices are referred to as "AB", "CD", etc.

◼ Polar amino acid residues are found at the surface

◼ Non polar amino acid residues (L, V, F, & M) are found at the interior except His E7 and HisF8

E and F

The heme of myoglobin lies in crevices of helices ____

a2B2

Hemoglobin A (HgA) is the major hemoglobin in adults

a2y2

Fetal hemoglobin (HbF)

a2s2

Sickle cell hemoglobin (HbS)

a2o2

Minor adult hemoglobin (HbA2)

Myoglobin and the B polypeptide of hemoglobin A

____ and the _______ have almost identical secondary and tertiary structures

Hgb tetramer

_____ is composed of two identical dimers, (a B)1 and (aB)2, dimers 1 and 2 respectively

hydrophobic interactions

Quaternary structure of Hemoglobin

Dimers are held together by ________ interactions

◼ Ionic and H-bonding also occur between the members of the dim

4

HEMOGLOBIN

◼ __ O2 binding sites per molecule

sigmoidal

HEMOGLOBIN

◼ The oxygen dissociation curve for Hgb is ____ in shape

one

OXYGEN BINDING TO MYOGLOBIN

◼ Can bind only ___ molecule of oxygen (one heme group only)

heme-heme interaction

It means that the binding of an oxygen molecule at one heme group increases the oxygen affinity of the remaining heme group in the same Hgb molecule

Homotropic Interaction/Effect

-Positive homotropic effect

–the homotropic effector increases the binding affinity for the same kind of ligand at other sites

–O2 in the hemoglobin system increases the O2 binding affinity of other sites

Negative heterotropic effector or allosteric inhibitor

– the effector decreases the binding affinity for the primary ligand

– protons, or CO2, or 2,3-BPG; all are negative heterotropic effectors of O2 binding to hemoglobin

Positive heterotropic effector, or allosteric activator

effector increases the binding affinity for the primary ligand

The Bohr Effect

effect of binding of protons (H+) and CO2 on O2 binding affinity of Hb

Deoxyhemoglobin

Increase protons or a lower pO2

Oxyhemoglobin

Decrease protons or an increase pO2

CO2

is a negative heterotropic effector (allosteric inhibitor) of O2 binding to Hb

60%

__% of HbCO are fatal

220X

The affinity of Hb for CO is ___X greater than for oxygen

2,3-bisphosphoglycerate (2,3-BPG) or "2,3-diphosphoglycerate" (DPG)

Most abundant organic phosphate in the red blood cells

METHEMOGLOBIN

-The heme iron is ferric than ferrous

– Oxidation of ferrous to ferric is caused by the side effects of drugs such as sulfonamides, or endogenous substance like hydrogen peroxide

– Can neither bind nor transport oxygen

sulfonamides, hydrogen peroxide

METHEMOGLOBIN

Oxidation of ferrous to ferric is caused by the side effects of drugs such as _____, or endogenous substance like ___

HEMOGLOBIN M

HisF8 has been replaced by tyrosine

HEMOGLOBIN S

V has replaced Glu6 of the B-subunit

MYOGLOBINURIA

Dark red coloration of urine following massive crush injury because myoglobin is released from damaged muscle fibers

Anemias

Reduction in the number of RBC or of Hb in the blood, or impaired production of erythrocytes (Vit.B12 deficiency)

THALASSEMIA

Partial or total absence of one or more  (- thalassemia) or  (-thalassemia) chains of hemoglobin

GLYCATED HEMOGLOBIN (HbA1c)

– Glucose enters the erythrocytes and glycosylates the e-group of lysine residues and the amino terminal of Hb

– Reflects the mean blood glucose concentration thus provides valuable information for management of Diabetes Mellitus

T form or “Taut” (tense) form

deoxy form of HgB

two ab dimers interact through a network of ionic bonds and hydrogen bonds

low oxygen-affinity form of hemoglobin

R form or relaxed form

binding of oxygen to Hgb (oxyhemoglobin

some ionic bonds and H- bonds between the aB diners are ruptured thus, the polypeptide chains have more freedom of movement

High oxygen-affinity form of hemoglobin

hyperbolic

the oxygen dissociation curve for Mb is a ___ shape

cooperative interaction (allosteric interactions)

occur when binding of one ligand at a specific site is influenced by binding of another ligand, which is called an “allosteric effector” or “modulator”

the second site it also called an allosteric site