MED 1102

PRESENTATION
KERATIN AND
Group members:
Crystal ManassehELASTIN
Sanjay

Veerasammy

Vasnie Ganeshnauth

Nicholas Elliot

Rehana Fareed

Sofyanna Scarce

Premanjali Panday

Khadija Yousuf

Narifa Ally

Savitree Sherman

Sumaiyah Baksh

Akleema Ahmad

Introduction

Keratin is a fibrous protein whose

rigid and tough structure makes it
a key structural component of hair,
nails, and unmineralized tissue

Keratin is a mechanically durable

and chemically unreactive protein

Keratins are the most diverse

classes of intermediate filaments

STRUCTURE

-Keratin

Coiled coil structure

Each subunit is a right handed

helix

Hydrogen bonding occurs within a

single strand

3.6 amino acids per helical turn

Cysteine linkages present

Rigid structure due to the

presence of disulphide bridges

Found mainly in mammals

Function Of Keratin
(-Keratin)
Hair strengthen and
prevents hair
strand breakage
Skin- protects
and maintains
the epidermis
Nails- toughen
nails

Types of Keratin
-Keratin

-keratin is classified under its xray difraction pattern.

It is rich in twisted plated sheets

Hydrogen bonding occurs in

neighboring polypeptide chains

The structure is either parallel or

antiparallel

There are 2.0 amino acid groups per

bend/turn

The side chains of -Keratins do not

contain cysteine linkages

-Keratins have a generally rigid

structure which found mainly in
reptiles and birds

Types of Keratin
-Keratin
Location

Function

Reptilian skin

Waterproofing
and prevents
desiccation

Feathers

Increases
elasticity and
aids in flight

Beaks and
Claws

Provides a
tough, rigid
structure to
beaks and
claws.

Spiders and
Insects

(Silk) Making
webs to catch
prey

Keratinocyte Synthesis
Produced by stem cells in
stratum basale
New cells push others toward
surface cells grow flat and fill
with vesicles (lipids)
Cells filled with keratin forms
epidermal water barrier

Keratinocyte
Diferentiation
Stratum

Basale

cuboidal cells, cells within this

layer proliferate, all cells
attached to the basement
membrane, one cell layer thick
Proteins- keratins K5 and K14,

integrins

Stratum

spinosum

cells increase in size,

increased cytoplasm:nucleus
ratio, cell layer 4-6 cells
thick, no further cell division
Proteins-keratins K1 and K10,
involucrin

Keratinocyte
Diferentiation (Contd)
Stratum

Granulosum

cells

become
elongated, usually 1-2 cell layers thick,
accumulate amorphous keratohyaline
granules.
Proteins- keratins K1 and K10, loricrin,
filaggrin, transglutaminase 3

Stratum

Corneum

keratinocytes contain thickened cell

envelopes, contain no nucleus,
imbedded in lipid matrix
Proteins- No new proteins expresses

Keratin Synthesis

Keratin Disorders
A keratin disease or keratinopathy is a genetic disorder on one of
the keratin genes.
Keratin Disorder

Gene Mutated

Epidermolysis bullosa
(EB)

Increased fluid filled

KRT1/KRT14-split in the blister formation or
lamina lucida of the
erosion of the skin and
cells of these genes.
mucous membrane
due to little or no
trauma at all

Autosomal dominant

KRT5/KRT14-cell
defective skin disease
within
degeneration
present at birth and is

the basal layer

of the
characterized by intraepidermis.
epidermal blistering.

Excess keratin in nail

beds and thickening of
Type 1: Keratin 6A or
nails, hyperkeratosis
Keratin 16
(thickening of the
outermost layer of the
Type 2: Keratin 6B or
epidermis), oral
keratin 17
lesions, pain and

Epidermolysis bullosa
simplex (EBS)

Pachyonychia
congenital

Signs/Symptoms

Keratin Disorder
Keratinopathic Ichthyosis
(KPI)

White Sponge Nevus

(Cannons Disease)

Gene Mutated

Signs/Symptoms

Missense
muations of:
Epidermolytic
ichthyosis-K1 and
K10.
Superficial
epidermolyic
ichthyosis-K2.

Superficial
ulcerations at early
stage, blistering,
hyperkeratotic
plaques with
verrucous scales on
the scalp, neck and
infragluteal folds
appears in later age.

Keratin 14 and
Keratin 13

Meesmann Corneal Dystrophy Chromosomes 12

and 17 of genes
(Stalker-Holt Syndrome)
KRT 3 and KRT 12
respectively.

Lesions on the
ventral surface of
tongue, labial
mucosa, alveolar
ridge and floor of the
mouth. They present
in birth and develop
in childhood.
Small cysts on the
corneal epithelium.
Patients with this
disease are

Clinical Application
Epidermolysis Bullosa Simplex
(Dowling Meara)

A 10 year old patient was admitted

to GPHC with the chief complaint
of abnormal blistering of skin and
abnormality in finger nails for 5
years now. His parents indicated
that he developed abrasions in his
oral cavity frequently at the time
of infancy and hence he did not
develop as expected. On physical
examination there was noted
hyperkeratosis on the hands and
soles of the feet. The patient also
shown indications of difficulty
walking, due to presence of
blisters and difficulty talking as a
result of abrasions.

ELASTIN

Structure of Elastin

A connective tissue protein

Rich in Proline and Lysine

Lysine residues responsible for

cross links which provide
immense tensile strength and
elasticity

Proline forms hydrophobic regions

It has large amounts of 4

hydrophobic amino acids: Proline,
Glycine, Alanine, Valine

Would not allow water to enter its

hydrophobic core

Polymer of tropoelastin
(soluble)

Has 765 amino acids

Has a random coiled

conformation

Soluble tropoelastin
contains primarily, glycine
& valine and modified
alanine and proline
residues

Polymerized by extensive
covalent cross-linking
(induced by lysyl oxidases)

Insoluble protein polymer

Desmosine and isodesmosine (derived from residues of

lysine)

Desmosine

Isodesmosine

Functions of Elastin

Provides properties of high extensibility and elastic recoil in

tissues

Can be stretched to several times their normal length, but

recoil back

Provides structural support to cells in tissues

Highly resilient to stress

Aids in maintaining original shape and size of organs and skin

Extremely durable, strong and tough

especially in skin where it has a half-life of ~70 years, but only

slowly replenished

Locations of Elastin

In the skin

The Walls of Arteries,

Lymphatic vessels

Elastic Cartilage and

Ligaments

Bladder

Lungs

Intestines

SEM images of elastin fibers purified from human skin biopsies of 6-yearold and 90-year-old individuals, respectively.
The morphological damage of the elastic fiber network is a consequence
of intrinsic aging.

ELASTIN DISORDERS
Cutis

Laxa

Williams

Syndrome:-

a)

Williams syndrome is classified as a microdeletion genetic disorder

caused during crossing-over or autosomal recombination.

b)

The missing segment of genes are lost

when the duplicated (homologous)
chromosomes cross-over during egg or
sperm formation.

)Marfans

Syndrome

WILLIAMS SYNDROME

Autosomal Dominant Disorder.

The clinical manifestations include a distinct

facial appearance, cardiovascular anomalies
that may be present at birth or later in life,
idiopathic hypercalcemia.

Low nasal bridge, low birth weight, failure to

gain weight appropriately, kidney abnormalities,
and low muscle tone.

Developmental delay coupled with strong

language skills, hypersensitivity to loud noises
and an outgoing personality.

WILLIAMS SYNDROME

Etiology: Williams syndrome is caused by the

spontaneous deletion of 26-28 genes on
chromosome #7 (7q 11.23).

Defect in the elastin synthesis

Supravalvular aortic stenosis

Diagnosis:- Distinctive physical characteristics,

FISH, kidney ultrasound, blood pressure check,
and echocardiogram.

Treatment
There

is no cure for Williams Syndrome and

people with the disease will have to be
treated and monitored for symptoms their
whole life.

Avoid

taking extra calcium and vitamin D in

the diet.

Physical

therapy, Developmental and

Speech Therapy and Special Ed. Classes

Surgery

is normally done to treat

Supravalvular aortic stenosis-patch
aortoplasty, tube graft replacement.

Cutis Laxa

Cutis Laxa (also called elastolysis), which is

Latin for loose/lax skin, is a disorder that afects
every 1 in every 2 000 000 individuals
worldwide. It is a disease usually characterised
by the unusual inelasticity of the skin. The
suferers skin hangs in loose folds. It is usually
an inherited condition, but some people may
develop this disease later in life. This condition
is known as acquired Cutis Laxa.

Etiology
Cutis Laxa is inherited in various ways, each
with their own characteristics. There are:

autosomal dominant.

autosomal recessive.

X- linked recessive.

Acquired Cutis Laxa.

Diagnosis

The preliminary diagnosis of Cutis Laxa may be

made by an expert physician upon examination
due to characteristic signs and symptoms.
However, this may be confirmed by a blood
test, gene examination or biopsy.

Treatment &
Management

To date, there is neither cure nor treatment

available; however, persons sufering from Cutis
Laxa may be treated with dapsone to control
swelling as it is a sulphone with anti-inflamitory
properties. Otherwise, the swelling may lead to
further sagging.

Management of Cutis Laxa includes cosmetic

surgery to remove unaesthetic sags (especially on
the face) and monitoring of smooth muscles and
cardiac tissue. Patients are also encouraged to avoid
smoking, alcohol consumption and prolonged
exposure to the sun as these activities may lead to
dehydration and further dermatological
complications.

Marfan Syndrome

This is a genetic connective

tissue disorder

It is autosomal dominant.
*This condition may
afect any gender and any
race. Because it is
auosomal dominant, one is
more prone to have it if
they have a close relative
with this disease.

It afects the skeletal,

cardiovascular and
respiratory systems, as well
as the eyes.

Marfan Syndrome
Signs and Symptoms

A tall, thin build.

Long arms, legs, fingers, and toes and flexible

joints.

Scoliosis, or curvature ofthe spine.

A chest that sinks in or sticks out.

Crowdedteeth.

Flat feet.

A heart murmur

Weak blood vessels walls that may rupture and

cause death( especially , the aorta)

Poor eyesight

Marfan Syndrome
Etiology

Etiology: caused by a defect (or mutation) in the

gene that tells the body how to make fibrillin-1
(FBN1gene).

Defect in microfibril formation.

Excess growth factors are released and

elasticity in many tissues is decreased, leading
to overgrowth and instability of tissues.

Retinal detachment, Aortic Dissection

Marfan Syndrome
Diagnosis and Treatment

Diagnosis:-Medical history, physical examination,

eye examination, echocardiogram.

Treatment:-

a)

Marfan syndrome requires a treatment plan that

is individualized to the patient's needs.

b)

Routine cardiovascular, eye, and orthopedic

exams and lifestyle changes.

c)

Medications: Beta blockers/calcium channel

blockers.

d)

Surgery (Aortic Dissection)-Standard open

surgery, Endovascular aortic repair, valve
replacement, coronary bypass.

References

Chamcheu, Jean Christopher et al. 'Keratin Gene Mutations In Disorders Of Human

Skin And Its Appendages'. Archives of Biochemistry and Biophysics 508.2 (2011):
123-137. Web. 3 Oct. 2015.

Keratin(2015). InEncyclopdia Britannica. Retrieved from

http://www.britannica.com/science/keratin Accessed on October 03 , 2015.

Lazier,J.2015. Williams Syndrome [Internet]. Available from http://

emedicine.medscape.com/article/893149-overview. Accessed on October 04th, 2015.

Learn Gentics, 2015. Wiiliams Syndrome [Internet]. Available from http

://learn.genetics.utah.edu/content/disorders/chromosomal/williams/. Accessed on
October 04th, 2015.

McLean, W. and Moore, C. (2011). Keratin disorders: from gene to therapy. Human
Molecular Genetics, 20(R2), pp.R189-R197.

Stoker,S.H, 2012. Organic and Biological Chemistry. Available from

https://books.google.gy/books?
id=z6o_PO4BhRQC&pg=PA384&lpg=PA384&dq=secondary+bonding+in+alpha+hel
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