What 3 things make up ground substance?
Glycoproteins
Glycoseaminoglycans
Proteoglycans
Ground substance participates in binding cells to fibers of what?
Fibers of connective tissues
What is a glycoprotein?
A protein with 1 or more attached sugars
GAGs are a family of what?
Heteropolysacharides
What are 2 important characteristics of GAGs?
Very hydrated
Very negative
What makes up proteoglycans?
A protein core with many GAG side chains
Bottle brush
What makes and secretes the large majority of extracellular matrix?
Neighboring cells
What is the most common cell of connective tissue?
Fibroblasts
What cells secrete dentin?
Odontoblasts
What cells secrete enamel?
Ameloblasts
What is the structure of tropocollagen?
3 helical strands
How do tropocollagen fibrils arrange themselves?
In a staggered array of parallel bundles
What causes striations in tropocollagen?
The alignment of every 4th molecule
Tropocollagen crosslinks via what?
Lysinonorleucine
Production of lysinornorleucine requires which enzyme?
Lysyl amino oxidase
What cofactor is needed for lysyl amino oxidase?
Vitamin B6 (pyridoxine)
What types of collagens are found in interstitial connective tissue?
Types I, II, III, V, XI
What is the most abundant collagen type
Type I
Most connective tissues have which collagen type?
Type I
What are some examples of tissues containing type I collagen?
Bone Tendon Skin Dentin Ligament Fascia Arteries Uterus
Type II collagen is a component of what type of cartilage?
Hyaline cartilage
Where is the 1 optometry correlation of type II collagen found?
In vitreous humor
Reticular fibers are made up of which collagen type?
Type III
Where are 3 places that type III collagen is found?
Skin
Arteries
Uterus
What is the predominant collagen type in periodontal ligament?
Type III collagen
T/F Type III collagen is often found in bone.
False
Which collagen type is the most abundant structural component of basement membranes?
Type IV
The lens has which collagen type?
Type IV
What makes type VIII collagen?
Endothelial cells
What makes type X collagen? When does this occur?
Chondrocytes
During endochondral ossification
Which collagen types are multiplexins?
Types XV and XVIII
Where are multiplexins found?
In basement membranes
Multiplexins have multiple triple helix domains and ___.
Interruptions
What is the precursor to tropocollagen?
Procollagen
What are the 6 steps of converting preprocollagen to procollagen?
- Signal peptide cleavage
- Registration peptides
- Hydroxylate proline and lysine
- Attach sugars to hydroxyproline and hydroxylysine
- Forme triple helix
- Package into vesicles
What are the 3 steps to convert procollagen to tropocollagen?
- Registration peptides cleaved off; forms insoluble tropocollagen
- Aggregation of tropocollagen forms fibrils
- Fibrils cross link
Which amino acid is involved in making desmosine cross links of elastin>
Lysine
The fibronectin network is secreted as what?
A dimer of 2 large monomers
Where are the 2 large monomers of the fibronectin network connected near?
C-terminals by disulfide bonds
What stabilizes the fibronectin network?
Transglutamase cross-linking
Unlike collagen, the fibronectin network assembly requires ___.
Cells
What does the fibronectin network do?
Helps organize extracellular matrix and mediate cell adhesion
Elastic fibers consist of an ___ component comprised of elastin.
Amorphous
Where are elastic fibers found?
Smooth muscle
Arteries
Elastic connective tissue
What are the triple stranded helices of elastin called?
Tropoelastin
Elastin is rich in which amino acids?
Glycine
Alanine
Lysine
Elastin fibers crosslink via what?
Desmosines
What is strange about the elastin helix?
It is not a true alpha helix
What makes up elastic fibers?
Fibrillins and other small proteins
Fibrillins are a family of large what?
Large glycoproteins consisting of EGF-like motifs
Where are fibrillins found?
Arterial linings
Heart valves
What “coats” elastin fibers?
Fibrillins
Elastin and fibrillins are ubiquitous where?
In connective tissues
What fibers are made first in fibrillin developments?
Oxytalan fibers
Why is elastin insoluble?
Extensive cross-linking
Laminins will bind to which ECM components?
Heparin
Type IV Collagen
Nidogen/entactin
Complexes of laminins and ___ provide structural organization to basement membranes?
Heparan sulphate, as well as “other molecules”
What 2 functions do laminins carry out in basement membranes?
Structural organization
Binding site for cells
What is the shape of nidogen/enactin?
Dumbell shaped
What is found on the ends of nidogen/enactin?
A laminin/collagen IV building domain on one end, and a self aggregating domain on the other
What separates the two ends of nidogen/enactin?
A rod-like connecting domain
What does nidogen/enactin do?
Dimerizes, then cross links laminin and type IV collagen
Nidogen/enactin is a 50 KD glycoprotein found where?
In all basement membranes
Fibulins contain __ EGF-like repeats?
9
What do fibulins bind to?
Laminins Nidogen Fibrinogen Collagen IV Other fibulins
What do fibulins do?
Thought to link cells to basement membranes
Fibulins are which type of protein?
Glycoprotein
In basement membranes, what forms an extensive, partially cross-linked network?
Type IV collagen
What do laminin 1 and nidogen do in the structure of basement membrane?
Form a second extensive network
What links the 2 major networks of basement membrane?
Nidogen binding to collagen IV
What do proteoglycans do in the basement membrane structure?
Intermix with the networks
What do fibulins bind in the basement membrane?
Nidogen
Laminin 5
Fibronectin
Collagen IV
In the structure of basement membrane, fibronectin binds to what?
All collagen
There is a log of ___-___ in the basement membrane.
Cross-linking
How many amino acids are in osteocalcin?
50
3 of the amino acids in osteocalcin are what?
Gamma-carboxyglutamate (Gla)
The 3 gamma-carboxyglutamates in osteocalcin are formed post-translationally in what type of reaction?
Vitamin K dependent reaction
What does osteocalcin bind to?
Binds calcium with high affinity
Adheres to hydroxyapatite crystals
Where is osteocalcin found?
Bone
Dentin
Cementum
What other role might osteocalcin play?
Regulating crystal growth (negative regulator)
What forms nanochains?
Amelogenin
What type of protein is amelogenin (fibrous or globular)?
Globular
Amelogenin self-assembles into what?
Nanospheres
What is the driving force for formation of parallel bundles of apaptite during enamel formation?
The self-assembly of amelogenin into nanochains (regulated crystal growth)
What is the hallmark cell of acute inflammation?
Neutrophil
What degrades elastin?
Neutrophil elastase
Elastase is which type of enzyme?
Serine protease
What inactivates elastase?
Alpha-1 antitrypsin
What does a deficiency in alpha-1 elastase result in?
Emphysema
What are the common symptoms of the group of 10 diseases in Ehlers-Danlos syndrome?
Fragile, hyperextensible skin
Hypermobile joints
Most forms of EDS result from defects in which types of collagen?
Types I, II, and III
What is the most sever type of EDS?
Type IV
What is the gene mutation associated with type IV EDS?
col3A1 gene
How is EDS type IV passed genetically?
Autosomal dominant
The overextensible tissues caused by EDS type IV can lead to what?
Arterial rupture (sudden death)
Intestinal perforation
Rupture of uterus
Easily bruised, translucent skin
What does the mutation of collagen alpha 1 (III) gene that causes EDS IV actually cause to occur?
Slow synthesis
Defective secretion
Increased susceptibility to degredation
Osteogenesis imperfecta is a group of how many diseases?
8
What causes osteogenesis imperfecta?
Defective chains assembling to form defective helices, then fibrils and fibers
What is the major symptom of EDS types VII A, B, C?
Dislocation of major joints
EDS types IVV A and B result from what mutation?
Mutations of collagen alpha 1 (I) or alpha 2 (I) gene
A mutation in the collagen alpha 1 (I) or alpha 2 (I) gene eliminates what?
The cleavage site for collagen N-protease
A lack of the cleavage site for collagen N-protease will cause what?
Incompletely processed collagens to assemble and form defective fibrils
How is EDS VII C passed genetically?
Autosomal recessive
EDS VII C (dermatosparaxis) results from a deficiency in what?
Collagen N-protease
Blue sclera results from ___ ___ caused by what?
Osteogenesis imperfecta
Defective type I collagen
What is the most common type of osteogenesis imperfecta?
Type I
What are some symptoms of type I osteogenesis imperfecta?
Easily fractured bones
Loose joints
Blue sclera
Which subtype of type I osteogenesis imperfecta results in dentinogenesis imperfecta?
Type IB
What is the problem in osteogenesis imperfecta type I?
Normal collagen, but not enough of it
What type of metabolism does cardiac muscle undergo?
Totally areobic
Cardiac muscle oxidizes what 2 things?
Glucose
Ketone bodies
How does cardiac muscle store energy?
As phosphocreatine
After a heart attack, which enzyme spikes the highest and fastest?
Troponin
What are the 3 enzymes to look for after a heart attack?
Lactate dehydrogenase
Troponin
Creatine kinase
After a heart attack, which enzyme takes the longest to spike?
Lactate dehydrogenase
What forms the globular “heads” of myosin?
Amino terminus
In myosin, 2 heavy chains coil from where?
Carboxy terminus
In myosin, light chains are associated with which region?
Head region
In myosin, cleavage with trypsin and papain result in what?
Heavy and light meromyosin
Which is the important calcium sensing troponin?
C troponin
What does I troponin do?
Inhibits
When a sarcomere contracts, which band gets smaller? Which band stays stable?
I band shortens
A band doesn’t change
What are the boundaries of a sarcomere?
Z disk to Z disk
