Biochemistry EVALS # 3

Lecture 8: The Extracellular Matrix

INTRODUCTION regeneration because it

 Case Study: A 7th month-old child fell over while contains the proteins
crawling who presented with a swollen leg. History required in order to fill the
revealed that at the age of one month, the baby had gap caused by injury.
multiple fractures on the right clavicle, right B. Functions of the ECM
humerus, and right radius at various ages of healing. a. Serves as anchorage
On radiographs, the affected leg revealed a fraction of b. Acts as a migration barrier (eg. Contact
a femur. Long bones were thin, had few trabeculae inhibition – cells touching something outside
and thin cortices. Radiographs of the skull revealed a them will stop them from moving or
mottled appearance. Careful questioning from the dividing)
parents ruled out child abuse. Father’s teeth were c. Acts as a migration track for movement of
slightly transparent and discolored. cells
 Explanation: Fracture at various ages of healing d. Reservoir for signals
should consider the possibility of child abuse. There e. Signal presenter
is a tentative diagnosis of osteogenesis imperfecta. f. Components can be degraded to perform
certain roles (eg. MMPs)
Lecture Content: g. Low affinity co-receptor
h. Ability to help cell detect biomechanical
1. Extracellular Matrix in Health and Disease forces – stretch or compress and detection
2. The Extracellular Matrix via connections between cells and matrix
3. Collagen
4. Elastin, Fibrillin and Tissue Flexibility
*The abovementioned functions cause change in
5. Structural Glycoproteins cell behavior.
6. Proteoglycans C. What is the role of ECM in certain disease states?
a. There must be a normal turnover where a
matrix has to be created and destroyed at
EXTRACELLULAR MATRIX IN HEALTH AND DISEASE certain points in order to maintain health.
A. What is the relationship between cells and their b. Excessive degradation of matrix (effected by
matrix? matrix metalloproteinases or MMPs – cut or
a. The relationship is reciprocal, a give and cleave proteins found in matrix; dependent
take relationship. on metals) or over-functioning of MMPs
i. The cells secrete the matrix will result in increase breakdown of
(fibroblast, osteoblast of bone, connective tissue which is related to
chondroblast of cartilages). The degenerative conditions like osteoarthritis.
cells change the composition of the This can also lead to conditions of the heart
matrix at various ages of life – – cardiomyopathy.
during development, as early as c. Overproduction of matrix (like in prolonged
embryonic life, in health and in tissue injury – filling of void that will signal
disease. quiescent fibroblast or myofibroblast to
ii. The matrix helps in various cell produce more) will result to fibrosis
processes. (scarring). Pathological fibrosis in internal
1. It helps shape cell polarity organs may be a major risk factor for certain
and maintains architecture conditions like cancer of the liver and breast.
by providing anchorage. Too much can be bad.
2. Biochemically, it regulates D. Cancer and ECM
material and information a. ECM may contribute to cancer pathogenesis
exchange by serving as a or the process by which cancer progresses.
reservoir for certain ECM may act as barrier to treatment (like
growth factors and ligands chemotherapeutic agents not being able to
(GFs, hormones, drugs). penetrate) and barrier or screen to immune
3. It plays a role in cell surveillance.
growth and migration by b. ECM can promote cancer progression by
guiding cells to target sequestering or generating growth factors
location. In cancer, matrix and angiogenic factors (in blood vessel
plays a role in metastasis. formation) and cell migration.
4. It is important in wound
healing and tissue
TRANSCRIBERS: Pammyyyy and Polin (pictures) 1 of 8
SUBTRANSHEADS: Pamela Aguila
 Biochemistry
Lecture 8: The Extracellular Matrix
THE EXTRACELLULAR MATRIX
 A network of macromolecules found extracellularly
embedded in a viscoelastic gel
Figure 1. Components of the extracellular matrix.
 Components are able to associate with each other
physically by entanglement, cross-linking or charge
dependent interactions
 Exists as two major types
o Basement membrane – more compact and
specialized; separates the overlying epithelia
from surrounding stroma; contains for
important macromolecules (Collagen Type
IV, laminins, HSPGs or heparin sulfate
proteoglycans like perlecan or agrin,
nidogen or entactin)
o Interstitial connective tissue matrix or
stroma – surrounds the cells; provides
scaffolding or support for tissues;
predominantly made up of Collagen Type I
and fibronectin
 Components are subdivided into three based on
function
o Structural proteins – provide mechanical
support
 Collagen – for tensile strength
which will prevent overstretching,
confers rigidity
 Elastin – confers elasticity and
extensibility; facilitates tissue
recoil; return to original shape
 Fibrillin-1 – found in microfibrils
and acts as scaffold for elastin
deposition; close relationship
between elastin and fibrillin-1
o Specialized glycoproteins – glycosylated
proteins; with carbohydrate moieties; play a
role in the assembly of matrix and act as
ligands by binding to cell-surface receptors
 Laminin - binding sites for most of
components
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
 Fibronectin – for adhesion and
migration
o Proteoglycans – gel forming molecules that
are made up of core proteins with attached
glycosaminoglycans; afford hydration and
sequester growth factors
o Other less important components include
growth factors, cytokines, enzymes
 Which properties are influenced by the composition
of ECM?
o Physical properties
 Tissue architecture and integrity –
repetitive; collagen and elastin
support tissues and regulate
distensibility – collagen will try to
stop tissues from being stretched
while elastin will allow stretching
 Proteoglycans will contribute to
hydration capacity (in cartilage)
o Biochemical properties
 Control of signaling processes by
the components
 Proteoglycans bind and present
growth factors
 Fibronectin and laminin stimulate
the cells via their connection with
integrin receptors
o Biomechanical properties
 Mechanosensing – ability of cells
to detect and respond to stretch and
compression through focal
adhesion complexes
 Focal adhesion complexes are
made up of integrins and a complex
of adapter and signaling proteins
that are found intracellularly linked
to actomyosin cytoskeleton
COLLAGEN
 Serves as the main structural component of the matrix
 Consists 25-35% of the total protein mass in the body
thus being the most abundant protein in the body
 Includes at least 28 types of helical proteins
 There are also “noncollagen collagens” – possess
collagen-like domains in their structure but do not
perform roles similar to what collagen does (eg.
Acetylcholinesterase, adiponectin, C1q, ficolin,
surfactant proteins SPA and SPD)
 Important in maintaining tissue architecture and
integrity
 Mediates cell-to-cell and cell-matrix interactions
 Classification of collagen is based on structure (form
follows function)
o Fibrillar collagens – contribute to tensile
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 Biochemistry
Lecture 8: The Extracellular Matrix
strength of tendons, cartilages, bone and
skin; most abundant is Type I collagen
o Network-forming collagens – tend to form
meshes or lattices that provide anchorage as
part of the basement membrane (Type IV
collagen) and may facilitate molecular
filtration thus allowing certain molecules to
pass through while limiting passage of
others
o Multiplexins – collagens with multiple triple
helix domains with interruptions; important
in production of endostatin in their C-
terminus
 Endostatin – inhibits cell migration
and angiogenesis therefore plays a
potential role in cancer therapy
o FACITs – fibril-associated collagens with
interrupted triple helices; found early in life
(embryonic and fetal skin and tendons)
o Transmembrane collagens – collagens
spanning the membrane
NOTE:
In a certain tissue or organ, collagen fibers are formed
by a hybrid of several collagen types. In skin, most predominant is
Type I collagen but there is also presence of Type III collagen.
 What is similar with collagen?
o Made up of tropocollagens
o Tropocollagen – triple-stranded right handed
superhelix held by hydrogen bonds and
covalent cross-links
o Three strands are wound together with each
strand termed as alpha chains
o Alpha chain – polyproline Type II helix;
made up of proline residues; extended left-
handed and stabilized by steric repulsion
present in bulky side chains
o Opposing handedness of superhelix and its
component strands makes it highly resistant
to unwinding
o Tropocollagen may encompass the entire
molecule or could be found as mere portion
of entire structure; non-helical domains
usually at the ends
o Alpha chains  Collagen molecules
(tropocollagen)  Collagen fibrils 
Collagen fibers
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
QUESTION: Is alpha chain similar with alpha helix?
No, alpha chain is found in collagen while alpha helix is
found in other proteins. Also, alpha helix is right-handed while
alpha chain is left-handed. In terms of rise, alpha helix has shorter
rise than alpha chain (0.15nm<0.30nm). In terms of pitch in a
particular turn, 3.6 amino acids for alpha helix while 3.3 for alpha
chain. Groups in the alpha chain are quite bulky therefore distance
is higher but this also stabilizes the alpha chains. For alpha helix,
intrachain H-bonds makes them stable.
Rise – distance between two consecutive amino acid residues
Pitch – length of one helical turn
Right-handed helix – makes a clockwise turn
Left-handed helix – takes a counterclockwise turn
 Collagen is uniquely rich in proline with a repeating
sequence of Gly-X-Y (X is proline and Y is usually
hydroxyproline).
 If there is a bulky side chain like proline, a small side
chain like glycine is needed.
 Glycine is able to fit into the crowded central core of
the helix with bulky groups found outside.
 Proline and hydroxyproline confer stability as well as
provide hydrogen bonding capacity with other triple
helices or proteins.
 Proline has the pyrrolidine side chain.
 Difference between proline and hydroxyproline is the
presence of a hydroxyl group at either position 3 or 4.
 How is mature collagen formed?
Figure 2. Formation of mature collagen
o Collagen undergoes extensive modifications.
o A precursor alpha chain winds and
assembles into a triple helix that is acted
upon by peptidases cleaving both ends
producing a shorter collagen molecule.
o Tropocollagen undergoes self-assembly to
produce fibrils which ultimately become a
collagen fiber.
o Inside the cell:
 Peptide is synthesized in the ER
and undergoes posttransational
modification.
 The precursor protein
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 Biochemistry
Lecture 8: The Extracellular Matrix
preprocollagen contains an
N-terminal leader
sequence which leads the
preprocollagen to the ER
lumen.
 The ER lumen is cleaved
after going into the lumen
producing a procollagen.
 Lysyl and prolyl residues
get hydroxylated with the
help of ascorbic acid (Vit
C) forming 3- and 4-
hydroxyproline and delta-
hydroxylysine.
 Glycosylation via O-
glycosidic linkage
happens in hydrolysyl
residues specifically at
noncollagenous domains
upon addition of
galactosyl then glucosyl
moieties.
 N-linked glycosylation
also happens to a certain
degree by involving amino
acid Asn.
 At C-terminal domains,
disulfide bridges form
between alpha chains
(means connection
between Cysteine
residues). It is acted upon
by protein disulfide
isomerase which then
initiates registration of
triple helices. Winding of
triple helix is from C-
terminus to N-terminus.
 Triple helix is transported
to Golgi for packaging in
secretory vesicles.
o Outside the cell:
 Collagen becomes insoluble and
more stable.
 Peptidases act on the N-
terminus and C-terminus
of the triple helix to cleave
the extension peptides
leaving behind shorter and
non-helical telopeptides.
 Triple helix undergoes
spontaneous self-assembly
to form insoluble fibrils in
a quarter-staggered
fashion.
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
 Quarter-staggered – a fiber
is displaced longitudinally,
roughly one-quarter that of
a consecutive fiber which
accounts for the
characteristic banded
appearance of collagen
fibers. This will
appropriately position the
Gly residues throughout
the helix.
 Fibrils form covalent cross-links
making them stronger.
 Lysyl and hydroxylysyl
residues are oxidatively
deaminated to form
aldehydes.
 Lysine and hydroxylysine
would contain amino
groups which are removed
to form aldehydes via
lysyl oxidase (Cu2+
dependent enzyme).
o Lathyrism –
chronically ingest
sweet pea or
taking of copper-
chelating drug
penicillamin
inhibiting lysyl
oxidase which in
effect will result
in bone
deformation and
demineralization.
 After aldehyde formation,
these aldehydes will form
cross-links either with
each other (aldol cross-
links) or with amino
groups of unosidised
lysine or hydroxylysine
residues to form
lysinonorleucine.
o Lysinonorleucine
– cross-link
found in both
collagen and
elastin.
 What dictates whether collagen will become fibrillar
or will become networks?
o In the presence of noncollagenous sequences
or interruptions and heavy glycosylation, the
triple helices are not able to associate fully
and thus are force to find another partner.
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 Biochemistry
Lecture 8: The Extracellular Matrix
o Gives rise to mesh-like structures.
 Disease conditions related to collagen:
o Osteogenesis imperfecta
 Brittle-bone disease
 Congenital condition characterized
by abnormal bone fragility
predisposing one to develop
fractures.
 Defective Type I collagen synthesis
 Type I collagen codes for
two genes: COL1A1 (pro-
alpha chain 1 (I)) and
COL1A2 (pro-alpha 2 (I))
 How important are glycyl residues
in collagen?
 Most mutations that
happen are connected to
glycine.
 Mutations when Gly is
replaced by bulkier
residues result in either
decrease collagen
expression, failure to form
triple helix and
instructurally abnormal
chains giving rise to
weaker collagen fibrils.
 An abnormal chain that
interacts with normal
chain will lead to
degradation of all chains
(procollagen suicide).
 Bone is predominantly made up of
Type I collagen.
o Scurvy
 Deficiency in ascorbic acid that
will lead to defective collagen
synthesis because there is impaired
activity of prolyl hydroxylase.
 To maintain proper collagen
formation, there is a need for
ascorbic acid by prolyl and lysyl
hydroxylases. The exact purpose is
to return iron to its oxidized state.
In the process of converting proline
to hydroxyproline, there is
reduction of iron to ferric form and
to return it back to ferrous form,
ascorbic acid is needed.
 Scurvy manifests with bleeding
gums, thin point bleeding under the
skin and poor wound healing.
o Menke’s disease
 Copper deficiency which impairs
the function of copper-dependent
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
enzymes in various tissues where
copper is required.
 People with Menke’s disease can
present with hypopigmented hair
because tyrosinase which is needed
in melanin synthesis is impaired
and tyrosinase is copper-dependent.
 Aside from Vitamin C, copper is
also needed for collagen formation.
Copper is a metal cofactor required
by lysyl oxidase for covalent cross-
links.
 Without cross-links, collagen
becomes weak.
 There can be aortic aneurisms
because the blood vessels
particualryly the aorta could
become weak and be prone to
rupture.
 There can also be presentation of
loose skin and fragile bones.
 Neurologic deficits are also
possible because of a dysfunctional
cytochrome C oxidase which also
requires copper.
o Cirrhosis
 In hepatocytes or liver cells, with
continuous injury, the typically
quiescent hepatic stellate cells and
fibroblast give rise to myofibroblast
which can produce excessive
collagen and dampen the activity of
the MMPs.
 Leads to hypertension of portal
venous circulation and end-stage
liver disease which will require
liver transplant.
 Type 4 collagen for basement membrane polymerizes
into hexamers or dodecamers stabilized by disulfide
bridges. It displays multiple interruptions allowing it
to be more flexible and form networks. Basement
membrane also contains laminins, heparan sulfate
proteoglycan and entactin.
ELASTIN, FIBRILLIN AND TISSUE FLEXIBILITY
 Elastin vs Collagen
o Elastin also synthesized as a precursor
peptide – tropoelastin.
o Tropoelastin undergoes hydroxylation at
proline residues only.
o Elastin is more hydrophobic than collagenn
where one out of seven amino acids is
actually a branched chain amino acid valine.
o Primary structure of elastin consist of
alternating hydrophilic and hydrophobic
domains.
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 Biochemistry EVALS # 3
Lecture 8: The Extracellular Matrix

Hydrophilic domains rich in lysine while STRUCTURAL GLYCOPROTEINS

hydrophobic is rich in valine.  Includes fibronectin and laminin
o Similar to collagen, upon secretion from  Have multiple binding sites for proteins and
cell, tropoelastin undergoes oxidative proteoglycans
deamination to form aldehydes aided by  Bind to cells through membrane receptors, in
lysyl oxidase. particular with RGD (Arg-Gly-Asp) domains
covalently
Table 1. Differences between elastin and collagen.  Fibronectin has particular domain with which it binds
ELASTIN COLLAGEN to cell-surface receptor.
Encoded by a single gene Encoded by several genes  Loss of fibronectin from surface of tumor cells could
Lacks a triple helix; random With triple helix contribute to metastasis.
coil allows stretch
No repeating structure in With Gly-X-Y repeating A. Laminin
glycine structures  Cross-shaped
No hydroxylysine Present hydroxylysine  Heterotrimeric (α, β, ɣ chains) glycoprotein
No carbohydrate present Contains carbohydrate held together by disulfide bridges
Desmosine cross-links (3 Aldol cross-links (allysine +  Chains undergo glycosylation in the ER
allysine + unoxidised lysine) allysine)  Upon secretion to extracellular space, chains
No extension peptides that Presence of extension self-polymerize in the presence of Calcium
have to be cleaved peptides  Laminin has binding sites for Type IV
collagen and other matrix components
 How does elastin allow tissue recoil?  Laminin is considered as the indispensable
o Through the weak interactions between the element of the basement membrane.
valine residues in the hydrophobic domains  Laminin binds to type IV collagen via a
o Changes in the tension among weak single chain protein entactin/nidogen and to
hydrophobic interactions allow elastin to cell-surface receptors (integrins and
relax and stretch. dystroglycans)
o Hydrophobic interactions are relatively  In cases where basement membrane gets
weaker than covalent interactions disrupted particularly in kidneys, there can
o Stretch will tend to loosen the hydrophobic be leakage of red blood cells or protein in
interactions while keeping the desmosine the urine. This happens when either the
crosslinks which are covalent in nature podocytes (foot-process bearing cells),
intact. endothelial cells or glomerular basement
o Property to stretch is important in the lungs, membrane gets damaged.
blood vessels, skin and ligaments. o What is the importance of
o Defective or decreased elastin may manifest glomerular basement membrane?
as pulmonary emphysema – lungs are able to  It provides a physical
expand but does not return to original shape barrier and also contains
and size; aortic stenosis – aorta becomes highly (-) charged
stiff; skin aging and wrinkles. proteoglycans which is
 How is fibrillin associated with elastin? important in filtering or
o Elastin exists as an amorphous substance keeping (-) charged
within an elastic fiber. proteins such as albumin
o Elastin is covered by a sheath of microfibrils in the glomerulus and
which contributes to the stability of elastin avoid from spilling into
fibers. the urine.
o Fibrillin is a predominant constituent of the  Negative acting with
microfibrils. another negative tends to
o In Marfan’s syndrome, mutation of fibrillin repel.
gene will lose the stability of elastin fiber  Damage of basement
manifesting loose joints, deformed spine, membrane will lose
flappy heart valves, lens dislocation and charged-charged repulsion
increase predisposition to rupture of the and albumin is able to leak
aorta. out.

TRANSCRIBERS: Pammyyyy and Polin (pictures) 6 of 8

SUBTRANSHEADS: Pamela Aguila
 Biochemistry
Lecture 8: The Extracellular Matrix
 If there is defect in type IV collagen, it is
called as Alport syndrome.
 Mutations affecting laminin is called
Pearson syndrome.
B. Fibronectin
 Can exist as a matrix component or as a
soluble protein in the plasma
 The matrix-associated type enhances cell
adhesion via integrins and mediates
migration of embryonic cells and
macrophages.
 The plasma-assocaited type is related to
blood clotting by cross-linking with
platelets.
 Structurally, it is a glycoprotein similar to
laminin.
 A dimer made up of two identical subunits
linked together at disulfide bridges near the
C-terminus.
 Different substrates binding to specific
domains of fibronectin
 How does fibronectin mediate cell adhesion
and migration?
o Fibronectin interacts with collagen
and with integrin receptor.
o This facilitates cell migration by
allowing cells to steer their way
through the matrix (acts like a
paddle).
o Integrins are transmembrane
proteins, that is not part of the
matrix, which permit cell-to-cell or
cell-to-matrix interactions.
Important in linking matrix to
cytoskeleton.
o The extracellular region interacts
with the matrix component in a
divalent cation dependent manner
meaning it will require cations to
be present. Signal is transmitted
from the matrix to the actin
cytoskeleton.
o Indirect connection between the
matrix and actin via integrins and a
series of attachment proteins (talin,
vinculin, alpha-actinin) through a
process called tensegrity.
o Integrins can also initiate
enzymatic cascades via associated
cytoplasmic kinases. They do not
possess enzymatic activity by
themselves.
PROTEOGLYCANS
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
 Known to be the ground substance
 Consists of glycosaminoglycans covalently attached
to core protein
 The core proteins are synthesized in the ER.
 Proteoglycans are mostly made up of carbohydrates
(95%) in contrast to glycoproteins.
 Vary in terms of nature of core proteins, the kind of
attached GAGs, tissue distribution and function
 May be present as integral membrane proteins where
they bind growth factors or as component of the
matrix
 Are proteoglycans and GAGs the same?
o GAGs or glycosaminoglycans – unbranched
repeating units of hexoses or hexuronic acid
and an amino sugar
o Hexose derivative of GAGs can either be L-
glucoronidase or the 5’ epimer L-iduronic
acid (except for keratan sulfate)
o For keratan sulfate, there is galactose
o Amino sugars are either D-glucosamine
(GlcNac) or D-galactosamine (GalNac)
(often in N-acetylated form)
o GAGs are highly (-) charged, avidly binding
water and cations afforidng hydration,
lubrication and compreessibility.
o Polyanionic nature of GAGs is due to
presence of carboxyl groups of uronic acids
as well as sulfate groups (O-esters or N-
sulfates).
o Sulfation at particular points in the molecule
is believed to result in GAG chain
termination.
 Examples of proteoglycans
Figure 3. Examples of proteoglycans
o Syndecan – membrane-bound proteoglycan
involved in tissue differentiation; rich in
heparan sulfate which allows syndecan to
bind growth factors
o Aggrecan – proteoglycan found in the
interstitial matrix; abundant in cartilages;
rich in chondroitin sulfate which allows
aggrecan to form
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 Biochemistry
Lecture 8: The Extracellular Matrix
hydrated gels and interact with collagen
providing scaffolding for tissues that need
high compressing and tensile strength
 How do GAGs attach to core proteins?
o In the ER and Golgi, GAGs covalently
attach to core proteins through three
linkages:
 O-glycosidic bond between a link
trisaccharide (Gal-Gal-Xylose-
Ser/Thr) – uniquely shared by most
proteoglycans
 O-glycosidic bond between N-
acetylgalactosamine and Ser/Thr –
seen in Keratan sulfate I
 N-glycosylamine bond between N-
acetylglucosamine and amid
nitrogen of Asn – seen in Keratan
sulfate II
 How are GAGs further modified?
o In the Golgi apparatus, GAGs undergo
various modifications aided by specific
enzymes and substrates.
o Addition of carbohydrate residues by
glycosyl transferases using nucleotide sugars
result in chain elongation.
o Linkage between adjacent amino sugars and
uronic acids is often alternatingly 1-4, 1-3
except in heparin and heparan sulfate where
it is uniformly 1-4.
o Sulfation could also take place through
sulfotransferases using PAPs
phosphoadenosine-5’-phosphosulfate)
source of active sulfate.
o Epimerization couls take place that will
convert glucoronyl to iduronyl.
 How are GAGs degraded?
o Within lysosomes, there must be a
continuous turnover of GAGs
o Core proteins are degraded by proteases
while the GAG chains are degraded by a
stepwise action of sulfatases (removal of
sulfate groups) and exoglycosidases
(removal of carbohydrate moieties)
beginning from external end of glycan chain.
o In the absence of enzyme in the pathway,
however, the entire process is halted and the
undegraded molecules accumulate within
the lysosomes giving rise
mucopolysaccharidosis (diagnosed
detecting specific GAG chain in serum or
urine followed by enzyme assay on
leukocytes or fibroblast).
 What are the major classes of GAGs?
TRANSCRIBERS: Pammyyyy and Polin (pictures)
SUBTRANSHEADS: Pamela Aguila
EVALS # 3
o Hyaluronic acid – nonsulfated, not linked to
core protein; seen in synovium, cartilage,
tendons; degraded by hyaluronidase
o Chondroitin sulfate – has glucuronic acid;
most abundant GAG particularly found in
the cartilage, tendons, ligaments and wall of
aorta; losses could contribute to
osteoarthritis
o Dermatan sulfate – has iduronic acid;
isolated in the skin; plays a role in
atherosclerosis by binding to LDL
o Keratan sulfate – most heterogenous;
different because it has sugar instead of
uronic acid; two types KS1 (seen in cornea)
and KS2 (seen in cartilage)
o Heparan sulfate – more N-acetyl groups and
less sulfate groups; predominantly found in
the basement membrane
o Heparin – most (-) charged; most sulfated; it
could be released free and serves as
anticoagulant; found in mast cell granules
REFERENCES:
1. Lecture Notes/ Recording
2. Study Guide of Doc VJ Mercado
th
3. Books (Harpers’ 30 Edition)
(3-
as
Things I heard while transcribing:
 “Ang dami huhuhu”
 “Tama na Doc”
 “Akala ko ba finally”
 “Gitna na ‘yung hati ng ulo ko di na ako natutuwa”
 “12 naaaa” –gutom
 “Independent sya” –referring to hyaluronic acid
 “Oh my God”
 “Kung single daw po kayo, magtanong kayo” –kung may questions
to daw kasi ‘yung class
by  “Sanay naman akong i-omit kasi less important ako”
 “Konti na lang”
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