Term
| where are GAGs and proteoglycans located |
|
Definition
| outside the cell or in organells |
|
|
Term
| what is the function of GAGs and proteoglycans |
|
Definition
| make gel matrix / ground substance in ECM with fibrous and adhesive proteins, flexible support for ECM, influence movement in ECM, make mucous viscous and lubricatin |
|
|
Term
| what type of fibrous proteins are in teh ECM |
|
Definition
|
|
Term
| what adhesive proteins are in the ECM |
|
Definition
|
|
Term
| describe the structure of a GAG |
|
Definition
| complex of negative heteropolysaccharide chains, unbranched, repeating acid/amino sugar units |
|
|
Term
| what are the options of amino sugars for a GAG |
|
Definition
| d-glucosamine or D-galactosamine |
|
|
Term
| what modifications can a GAG amino sugar have, what does this do to the molecule |
|
Definition
| acetlyation makes it positive, sulfation makes it negative, cannot be both |
|
|
Term
| what are the options for an acid sugar in a GAG |
|
Definition
| D-glucronic acid, L-iduronic acid |
|
|
Term
|
Definition
| because the acid sugar is carboxylated and it is negative |
|
|
Term
| what acid sugar does ketatan sulfate have |
|
Definition
| galactose instead of acid sugar |
|
|
Term
| what does the negative charge of a GAG make it do |
|
Definition
| extend in solution, repell eacother, develop hydration spheres |
|
|
Term
| what happens when GAGs are compressed together |
|
Definition
| they repulse, releasing water |
|
|
Term
| what does the result of GAG compression give some body fluids the ability to do, give examples |
|
Definition
| makes synovial fluid absorptive and lubricating, makes vitreous humor of the eye absorptive, makes mucous lubricating |
|
|
Term
|
Definition
| by monomeric composition, glycocidic linkage, degree and location of sulfates |
|
|
Term
| what is a proteoglycan composed of |
|
Definition
|
|
Term
| what GAG cannot participate in a proteoglycan |
|
Definition
|
|
Term
| what is the prodominent component of a proteoglycan |
|
Definition
|
|
Term
| what are examples of proteoglycans |
|
Definition
| chondroitin sulfate, keratin sulfate |
|
|
Term
| how are proteoglycans grouped |
|
Definition
| into gene families by structure |
|
|
Term
| what are the gene families of proteoglycans |
|
Definition
| aggrecan, versecan, neurocan, brevican |
|
|
Term
| what proteoglycan family is found the most in cartilage |
|
Definition
|
|
Term
| what is the most common GAG-protein linkage, describe it |
|
Definition
| trihexoside: (gal-gal-xylose)-ser of protein with a O-glycocidic bond |
|
|
Term
| explain the structure of a proteoglycan aggregate |
|
Definition
| proteoglycan monomeres attached to a hyaluronic acid core with the bonds stabilized by linker proteins |
|
|
Term
| describe the structure of a proteoglycan |
|
Definition
| GAGs connected to a protein core connected by covalent bonds |
|
|
Term
| where does GAG synthesis occur |
|
Definition
|
|
Term
| what is needed for GAG synthesis |
|
Definition
| UDP-derivatives of acidic and amino sugars, glycosoltransferases to catalyze |
|
|
Term
| where are amino sugars made the most |
|
Definition
|
|
Term
| what molecule do you begin amino sugar synthesis with |
|
Definition
|
|
Term
| what is fructose-6-phosphate turned into in amino sugar synthesis, how |
|
Definition
| glucosamine-6-phosphate, using glutamine, releasing glutimate, using transamidase |
|
|
Term
| what happens to glucoasmine-6-phosphate before it can be turned into an amino sugar |
|
Definition
|
|
Term
| what happens to an acetlyated glucoasmine-6-phosphate |
|
Definition
| it is either turned into salic acids (NANA) or it goes through a UDP glucose like synthesis to make UDP-acetylglycoseamine or UDP-acetylgalactoamine |
|
|
Term
| how are acidic sugars made |
|
Definition
| UDP-glucose has 2NAD and water added using UDP glucose DH to make UDP-glucuronic acid |
|
|
Term
| what is the epimere of glucuronic acid |
|
Definition
|
|
Term
| what are the functions of UDP-glucuronic acid |
|
Definition
| detoxification of insoluble compounds, make GAGs, detoxify, precursor for vitamin C |
|
|
Term
| what types of insoluble compounds does glucuronic acid detoxify |
|
Definition
| bilirubin, steroids, drugs (morphine) |
|
|
Term
| what are other sources of glucuronic acid |
|
Definition
| diet, lysosomal degration of GAGs, urionic acid pathway |
|
|
Term
| describe the sythesis of the core protein of a GAG |
|
Definition
| translated in ER then put into ER lumen to be taken to golgi where it is glycosylated by glycosyltransferases |
|
|
Term
| what has to happen before the side chain carbons can be added to a GAG |
|
Definition
| a short carbohydrate link needs to be made to the core protein |
|
|
Term
| explain the elongation of GAG carbon chains |
|
Definition
1. UDP-xylose is added to make a xylose go onto the existing carb linkage with a SER or THR resudue
2. 2 galactose are added
3. altering acidic/amino sugars are added
4. epimerization of some of the glucuronyl to L-iduronyl |
|
|
Term
| how are sulfates added to a GAG |
|
Definition
| sulfotransferases add aulfate to the carbohydrate |
|
|
Term
| what are chondrodystrophies a result of |
|
Definition
| defect iin sulfation of GAGs |
|
|
Term
| what type of inheritance is chondrodystrophys |
|
Definition
|
|
Term
| what are the symptoms of chondrodystrophys |
|
Definition
| abnormal bone proportions, hearing, eye, motor function problems, obesity |
|
|
Term
| why is chondrodystrophy considered a genetic hayline disorder |
|
Definition
| hayline fills bone gaps in development when new cartilage is being made, failure to do this misshapes joints and causes early osteoarthritis |
|
|
Term
| what are the types of chondrodystrophys |
|
Definition
| short trunk withh normal limbs, short limbs with normal trunk |
|
|
Term
| how do you diagnose chondrodystrophy |
|
Definition
| parent testine, x-ray, charting bone growth |
|
|
Term
| what disease category is achondroplasia in |
|
Definition
|
|
Term
| what type of inheritence is achondroplasia |
|
Definition
|
|
Term
| what is defective in achondroplasia |
|
Definition
|
|
Term
| what is the main symptom of achondroplasia |
|
Definition
|
|
Term
| what are the three basic steps of GAG degration |
|
Definition
1. GAG brought in by phagocytosis
2. endosome fuses with lysosome
3. hydrolytic enzymes degrade |
|
|
Term
| what is required to complete digestion of GAGs |
|
Definition
|
|
Term
| describe how acid hydrolases degrade GAGs |
|
Definition
| polysaccharides are broken down by endoglycosidases into oligosaccharides which are cleaved at the last end added in synthesis to make monosaccharides |
|
|
Term
| what causes mucopolysaccharidoses |
|
Definition
| deficiency in lysosomal hydrolyases that degrade hepran sulfate or dermatin sulfate letting GAGs accumulate in tissue and urine |
|
|
Term
| what are the symptoms of mucopolysaccharidosis |
|
Definition
| cellular and ECM deformities, mental retardation, gradual deteroiration, normal at birth |
|
|
Term
| what type of inheritence is mucopolysaccharidoses |
|
Definition
| autosomal recessive except hunter |
|
|
Term
| how are mucopolysaccharidoses diagnosed |
|
Definition
| evaluating cellular lysosomal hydrolyases |
|
|
Term
| how are mucopolysaccharidoses treated |
|
Definition
| marrow or bord blood transplant ini hurler and hunter sydromes, enzyme replacement, transplant of macrophages so they can degrade GAGs in the ECM |
|
|
Term
| what are the mucopolysaccharidose diseases |
|
Definition
| hurler's, sandlippo, hunters, and sly syndromes |
|
|
Term
| which is the most severe mucopolysaccharidose |
|
Definition
|
|
Term
| what are the symptoms of hurler's syndrome |
|
Definition
| corneal clouding, mental retardation, dwarfism, coarse facial features, coronary artery deposition leading to ischemia and death |
|
|
Term
| what causes hurler's syndrome |
|
Definition
| dermatan sulfate and hepran sulfate deficiency |
|
|
Term
| what is the treatment of hurler's syndrome |
|
Definition
| marrow or cord blood transplant, enzyme replacement |
|
|
Term
| what causes sanflippo syndrome |
|
Definition
| defect in 4 enzymes that remove sulfated or acetlyated glucoasmine from hepran sulfate |
|
|
Term
| what are the main symptoms of sanflippo syndrome |
|
Definition
| nervous system disorders, retardation |
|
|
Term
| what are the non main symptoms of sanflippo syndrome |
|
Definition
| behavorial, coarse facial features, diarrhea, full lips, heavy eyebrows, sleep problems, stiff joints, walking problems |
|
|
Term
| what causes hunter's syndrome |
|
Definition
| cannot degrade dermatan sulfate and hepran sulfate |
|
|
Term
| what type of inheritence is hunter's syndrome |
|
Definition
|
|
Term
| what are the symptoms of hunter's syndrome |
|
Definition
| NO corneal clouding, physical deformity, retardation, coarse facial features, growth deficiency |
|
|
Term
| what is the treatment for hunter's syndrome |
|
Definition
|
|
Term
|
Definition
| cannot degrade dermatan sulfate and hepran sulfate |
|
|
Term
| how is sly syndrome treated |
|
Definition
|
|
Term
| what are the symptoms of sly syndrome |
|
Definition
| depressed nasal bridge, epicanthic folds, long philtrum, thin upper lip, hypertrichosis (hair) |
|
|
Term
| describe the structure of glycoproteins |
|
Definition
| short, often branched, oligosaccharides covalently attached, glycosylated secretory proteins |
|
|
Term
| where are glycoproteins in the cell |
|
Definition
| the carb part is external to the cytosol so either in an organell or outside the cell |
|
|
Term
| what are the functions of membrane bound glycoproteins |
|
Definition
| cell surface recognition, surface antigens, ECM formation, mucous of GI and urogenital |
|
|
Term
| what are the functions of non-membrane bound glycoproteins |
|
Definition
| globular plasma proteins, lysosomal proteins |
|
|
Term
| what is another name for non-membrane bound glycoproteins |
|
Definition
|
|
Term
| describe the carb content of a glycoprotein |
|
Definition
| short carb chain, no repears, could be negative, variable amount of chains, has either N, O or both glycocidic bonds |
|
|
Term
| what are the links between carb and protein in a glycoprotein |
|
Definition
|
|
Term
| what does a N-glycocidic bond connect |
|
Definition
|
|
Term
| what does O-glycocidic connect |
|
Definition
| sugar to -OH of SER or THR |
|
|
Term
| when can an O glycocidic bond be used |
|
Definition
| in ECM or membrane for a variety of sugars |
|
|
Term
| what sugar shape does O glycocidic bonds work for |
|
Definition
|
|
Term
| what do N glycocidic bonds need to be used |
|
Definition
| core pentasaccharide with a complex oligosaccharide or a high mannose oligosaccharide |
|
|
Term
| what is a complex oligosaccharide |
|
Definition
| diverse additional sugars |
|
|
Term
| for the synthesis of the protein in glycoproteins, what needs to happen first before it will even work |
|
Definition
| the protein needs to have a cell signal to adress it to the proper location or it will become a cytosol protein |
|
|
Term
| how are glycoprotein proteins directed to the RER |
|
Definition
| N terminal hydrophobic sequences |
|
|
Term
| once in the golgi, what happens to the protein destined for a glycoprotein outside the cell |
|
Definition
| it is packed into vesicles that fuse with the cell wall and release it |
|
|
Term
| once in the golgi, what happens to the protein destined for a glycoprotein inside the cell |
|
Definition
| integrated into the ER membrane, passed through the golgi, packaged, and delivered to the cell membrane |
|
|
Term
| how is the carb part of a glycoprotein made |
|
Definition
| nucleotide sugars are made into oligosaccharides which are covalently attached to an amino and glycosylated |
|
|
Term
| how is the area of glycosylation determined on a carb destined for a glycoprotein |
|
Definition
| depending on the 3D structure |
|
|
Term
| describe the synthesis of an O-linked glycoprotein |
|
Definition
| protein from teh ER lumen or membrane goes to the golgi and N-acetylgalactosamine is transfered from UDP to SER/THR on the protein with glycosyltransferases |
|
|
Term
| what needs to first happen to the protein in N-linked glycoprotein synthesis |
|
Definition
| core glycosylation by protein oligosaccharide transferase |
|
|
Term
| describe O-linked glycorpotein sythesis |
|
Definition
1. mannosyl and glycosyl removed passing through ER
2. in golgi a variety of sugars are added
3. phosphorlyation at specific mannoses
4. sent to mannose-6-p receptors on the golgi
5. golgi sends it to the lysosome |
|
|
Term
| if making a high level mannose glycoprotein, how does this alter the synthesis |
|
Definition
| after adding the sugars in the golgi, no more processing is needed |
|
|
Term
| what is the terminal sugar on a N-linked glycoprotein |
|
Definition
|
|
Term
| what type of disease is I cell disease |
|
Definition
|
|
Term
| what causes I cell disease |
|
Definition
| acid hydrolyase enzymes dont target lysosomes because mannose on glycoproteins are not phosphorlyated |
|
|
Term
| what are the symptoms of i cell disease |
|
Definition
| skeletal abnormalities, restricted joints, coarse features, phsycomotor impairment, death before age 8 |
|
|
Term
| how are glycoproteins degraded |
|
Definition
| acid hydrolases in the lysosome remove particular components then the rest is broken down by exoenzymes enzymes |
|
|
Term
|
Definition
| removes things in reverse order |
|
|
Term
| what is the inheritence of oligosaccharidosis |
|
Definition
|
|
Term
| what causes oligosaccharidosis |
|
Definition
| lysosomal hydrolyase deficiency leads to accumulation of partially degraded glycoproteins |
|
|
Term
| what disease is oligosaccharidosis similar to |
|
Definition
|
|
Term
| what is a symptom of oligosaccharidosis |
|
Definition
| sometimes immunodeficiency |
|
|
Term
| what is a specific disease that falls in the oligosaccharidosis category |
|
Definition
| alpha mannosidosis type 1 |
|
|
Term
| what causes alpha mannosidosis type 1, what does this lead to |
|
Definition
| no alpha-mannosidase, early death |
|
|
Term
| how can alpha mannosidosis type 1 be detected |
|
Definition
| mannose oilgosaccharides in urine |
|
|
