THE CELL TIM Flashcards
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what is the matrix very plentiful in?
connective tissue, forming the framework of the body like the bone, skin, tendons, lens of the eye
in the case of the epithelium, what does the matrix form? what is the key role of the matrix?
basil lamina
development, migration, proliferation, shape and function of cells
what are the two important cells in the fibroblast that give rise to specialized connective tissue?
chondroblast, make cartilage
osteoblasts, make bone
what are the matrix elements?
GAGs (form proteoglycans) fibrous proteins (collagen, elastin, keratin for structure and fibronectin, laminin as adhesives)
in addition to these proteins, cells also make and incorporate into their cell membrane, these proteins allowing cells to attach to the scaffolding and hold together as a tissue?
integrins and selectins
collagen, elastin, keratin (scaffold)
intern, selectin (cell binding)
fibronectin, laminin (adhesion)
these molecules are incorporation into the matrix, highly hydrated and help keep the tissue inflated?
what is the benefit of being hydrated?
GAGs and proteoglycans
elastin (stretchability)
collagen (strength)
proteoglycans (compressibility)
diffusion of nutrients, signals and wastes
T/F, GAGs are unbranched polysaccharide chains composed of repeating disaccharides?
T
what is unique about the disaccharide of the GAG?
one of the sugars is an amino sugar and sulfated, making them negative thus attracting water and causing neighboring chains to repel
the second sugar is a uronic acid, adding more negative charge
so,
N-acetylglucosamide and glucronate
or
N-acetylglucosamide and iduronate
what are the four main GAG groups?
hyaluronan
chondroitin sulfate and derma tan sulfate
heparan sulfate and heparin
keratan sulfate
what is unique about the GAGs?
they don’t fold easily
negative charges make them extend
attracts Na+ and water creating turgor in tissue (cartilage in joints, providing cushioning)
this is the simplest of the GAGs, consists of 25,000 non-sulfated disaccharides each of which contains 1 glucuronate and 1 N-acetylglucosamine, found in all tissue and abundant in early embryos?
Hyaluronan
in the adult this GAG is important as a space filler/retainer, like styrofoam?
Hyaluronan
this GAG is important in wound repair and an important component of synovial fluid as lubricant?
Hyaluronan
these specific hyaluronan building proteins are found in the matrix and on cell membranes?
hyaladherins
how are hyaluronans different from the other three classes of GAGs?
simply a GAG
much larger than other GAGs
contains no sulfate
other GAGs have combination of different disaccharides
this GAG is similar to Hyaluronan but shorter and each disaccharide consists of glucuronate + N-acetylgalactosamine
also, this gag, in the same group has carboxyl groups epimerized on a glucuronate resulting in this GAG
chondroitin sulfate
dermatan sulfate
this GAG has a high number of sulfates added to the backbone, the very negative charge of heparin is important in binding antithrombin III and has a potent anticoagulant effect
heparan sulfate and heparin
this GAG has repeating B-1-3 and B-1-4 bonds but each disaccharide is made of galactose and N-acetylglucosamine?
this is also the shortest of the GAGs and the carbon 6 is sulfated
Keratan sulfate
how are proteoglycans distinguished from glycoproteins?
up to 95% of the mw is sugar
types of sugars vary and many GAGs are highly structured except hyaluronan
GAGs are repeating, straight chain disaccharides
this type of proteoglycan is a major constituent of cartilage, it has over 100 GAGs or about 1 GAG every 20 amino acids?
other proteoglycans have only 1-10 GAGs attached. This proteoglycans is made by fibroblasts and has only 1 GAG chain?
aggrecan
decoran
what are the functions of proteoglycans?
regulation of signal molecule activity (FGF, TGF-B)
organizing the ECM
cell surface receptors
this proteoglycan contains many Heparan Sulfates and functions in the basil lamina of the renal glomerulus participating plasma filtration during urine formations?
perlecan
this type of proteoglycan is used in organizing the ECM, found in cartilage?
aggrecan aggregate
this type of proteoglycan is a cell surface receptor because their core protein is transmembraneous? this glycoprotein serves an important role in orienting the ECM to the cytoskeleton?
syndecans
this proteoglycan is 130 GAGs, found in cartilage, and functions as mechanical support, aggregates with hyaluronan?
aggrecan
this proteoglycan is 1 GAG long, found in connective tissue, and functions to bind type I collagen and TGF-B?
decoran
this proteoglycan is 1-3 GAG long, found in the fibroblast and epithelial cells, and functions for cell adhesion and binds FGF?
syndecan-1
what is the major protein of the matrix?
collagen
these are a family of fibrous proteins that are secreted by connective tissue cells, as well as by other cells?
collagens
what are collagens rich in? what are these important in?
proline, lysine and glycine
calcified tissue
what type of chain comprises the three collagen polypeptide chains to make a collagen molecule?
alpha chains
what are the 5 abundant amino acids found in the alpha chain?
glycine lysine proline hydroxylysine hydroxyproline
this collagen type accounts for 90% of all body collagen and found in bone, skin, tendons, cornea, and internal organs?
type I, 2 alpha 1 I chains, and 1 alpha 2 I chain
what’s the difference in alpha chain?
each alpha chain is 1000 aa long and made of repeating 3 aa sequences
so every 3rd AA in alpha1 or alpha2 is glycine:
every 3rd AA in a1 is HP
X or Y is proline
z is HP or HL
T/F, hydroxyproline and hydroxylysine are common outside of collagen?
F, rare, they are a good collagen marker and produced via post translational processing
how are proline and lysine R groups hydroxylated?
by Prolyl Hydroxylase or Lysyl Hydroxylase
how is proline or lysine converted to hydroxyproline or hydroxylysine?
prolyl hydroxylase or lysyl hydroxylase with oxygen, alphaketogluturate and ascorbate
what does a Vit C (Ascorbate) deficiency reduce and cause?
hydroxylation, tripe helix is impaired and weak bones and vessels result
scurvy
where do the disulfide bonds form in pro collagen?
form between 3 pro alpha chains near their carboxyl terminal and the triple helix begins to form from that point
where is pro collagen found? what and where are the enzymes used in the formation of collagen?
outside cells
N-Procollagen peptidase
C-Procollagen peptidase
what is a collagen fibril? how are the cross links made to form this collagen fibril?
made of many collagen molecules
lysyl oxidase
what is the result of many collagen fibrils?
collagen fiber
what digests collagen?
collagenases
what amino acids are mainly found in elastin?
proline and glycine and no hydroxylysine and little hydroxyproline
what provides the elasticity of elastin? what are the ends rich in, like what AAs?
the hydrophobic R groups, provides clumping
alanine and lysine, form alpha helical arrays and cross links with other elastin molecules
what is the result when 4 elastin molecules can link at a single point?
desmosine
what is another important component of elastin?
fibrillin
this glycoprotein is large and involved in maintaining the integrity of elastic fibers?
fibrillin
this syndrome results from a mutation in the fibrillar gene and the aorta is prone to rupture?
marfan’s syndrome
in normal tissue development this is displaced as elastin assembles?
microfibril scaffolding
this is made by the liver and circulates in blood? It inhibits this and therefore protects elastin degradation?
alpha1-antitrypsin
neutrophil elastase
this enzyme is important for maintaining lung elasticity and without it, emphysema develops?
alpha1 antitrypsin
keratins have an assembly rich in these kinds of polypeptides? what give shape?
cysteine rich polypeptides forming tough stiff fibers in hair, nails, and epidermis
disulfide bonds
this is a protein used for adhesion? It is a glycoprotein in a dimer shape of 2 large subunits linked to each other by 2 disulfide bonds with each subunit containing 4 binding sites
fibronectin
this glycoprotein is also used in guiding cell migration during development?
fibronectin
this is one of the first matrix proteins made during development forming the initial scaffolding of the basal lamina and this is a cross shaped protein used for adhesion and has a eell binding region and a heparan sulfate binding region
laminin
this is a flexible mat of specialized matrix that underlies all epithelial cell sheets and tubes?
basal lamina, also surround individual muscle, fat and schwann cells
these proteins sere as cell surface receptors to connect cells to MAT?
interns and seletins
T/F, cell shapes matrix and matrix shapes cell
T
what is unique about integrins?
these trigger intracellular signal cascades and binding to matrix alters gene expression
what are the functions of the bone?
support and shape protection allow movement calcium and phosphate homeostasis blood cell production
this provides the tensile strength to our bones?
collagen
what do osteoblasts secrete at the surface of the bone? what results from the hydroxyl ion secretion causing the calcium and phosphate to become supersaturated?
calcium
phosphate
hydroxyl ion
hydroxyapatite
(Ca10(PO4)6*(OH)2)
what is the major protein of the matrix?
collagen
this molecule is a matrix protein that is long, stiff, a triple helix of three polypeptide chains? what are these polypeptide chains called?
collagens
alpha chain
collagens are rich in what amino acids?
proline, lysine, and glycine, also hydroxyproline and hydroxylysine
which amino acids are important for calcified tissue?
proline and lysine that are hydroxylated
what are the different forms of collagen?
gel form in ECM
bundle form in tendons
stacked form in cornea
angled bundle in bone
what type of collagen is found in connective tissue and how many different types are there?
fibrillar
5 types
I,II,III,V,XI
this type of collagen accounts for 90% of all body collagen?
type I
found in bone, skin, tendon, cornea and internal organs
what is unique about the collagen types?
what is unique about the alpha chains?
different combinations of alpha chains that form different collagens with various functions
each alpha chain is 1000 aa long, made of repeating 3 aa sequences
alpha 1 and alpha 2
what is unique about the 3rd AA in alpha 1?
what about X or Y?
what is z?
hydroxyproline
proline
hydroxyproline and hydroxylysine
T/F, you can find hydroxyproline and hydroxylysine outside of collagen?
false
where is the prepro alpha polypeptide made? this chain is produced by cleaving the signal peptide and is also modified how in the RER and Golgi?
what enzyme is used in the hydroxylation of proline and lysine? in addition, what else is used?
rough endoplasmic reticulum
pro-alpha chain
hydroxylated
prolyl and lysyl hydroxylase; O2, alpha ketogluturate, ascorbate, deficiency in Vit C or ascorbate results in scurvy
in collagen synthesis, what enzyme is used to form cross links?
lysyl oxidase
many collagen fibrils associate to form this?
collagen fiber
half life of collagen?
measured in months
what enzymes are used in the digestion of collagen?
collagenase
what is used to facilitate the attachment of osteonectin to collagen which forms hydroxyapatite?
osteocalcin chaperones
what stimulates osteoblasts?
inhibits?
growth hormone insulin estrogen androgens vitamin D calcitonin
cortisol
what stimulates osteoclasts?
inhibits?
PTH
Vitamin D
cortisol
thyroid hormone
estrogen
androgens
calcitonin
Normal concentration of Ca and HPO4 in the ECM?
Calcium 2.4 mM
HPO4 1.2 mM
what is the CaHPO4 solubility product?
within 4 mM, if more after multiplying Ca and HPO4, calcium precipitates out of solution
what are the three important hormone in regulating Ca in the body?
PTH
1,25-Dihydroxy Vitamin D3
Calcitonin
this polypeptide hormone is critical for min to min regulation and you have the increase in plasma Ca and decrease in plasma PO4?
PTH
this steroid hormone is important for long term regulation and increase in Ca and HPO4 via absorption?
1,25-Dihydroxy Vitamin D3
this polypeptide hormone is not essential in humans and acts to decrease plasma Ca and HPO4
Calcitonin
what is the stimulus for PTH release?
decrease concentration of plasma calcium
what are the primary, secondary and tertiary PTH targets?
bone increase plasma Ca and HPO4
proximal and distal tubules of the kidneys Retain plasma Ca and lose HPO4 in urine
proximal tubules of the kidneys
increase Ca and HPO4 in gut
what organs are required in the synthesis of 1,25-Dihydroxy Vitamin D3?
gut
skin
liver
kidney
which organs add the hydroxyl groups to the synthesizing 1,25-Dihydroxy Vitamin D3?
liver
kidney
what are the stimuli for 1,25-Dihydroxy Vitamin D3?
increase PTH
decrease HPO4
what is the primary, secondary, tertiary target of calcitriol?
what is the significance if PTH is present?
intestinal cells (increase plasma Ca and HPO4, increase absorption)
bone (increase plasma Ca and HPO4, increase absorption)
kidney(increase Ca and HPO4 retention, increase retention)
the 1,25-D3 is overridden by PTH so only Ca is retained
how does vitamin D deficiency lead to rickets?
decrease Ca absorption leading to bone breakdown
what are the stimuli for calcitonin?
what does it prevent?
plasma Ca and/or digestive hormones
post prandiol hypercalcemia
what is the primary target of calcitonin? what is the effect?
bone
decrease Ca and HPO4
what is significance of hyperphosphatemia?
no endocrine response necessary because filtered HPO4 load in kidney exceeds Tmax and lost in urine
