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Block 3 > Week 3 > Flashcards

Week 3 Flashcards

1
Q

What is a complex polysaccharide?

A
  • Any oligosaccharide with more than one type of sugar residue
  • usually attached to proteins, protein anchors or lipids
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2
Q

What does a glycotransferases do?

A
  • Transfers a monosaccaride from a donor to an acceptor
    • Donor - UDP, GDP, CMP, Dolichol
    • Acceptor - protein, lipid, non-reducing end of another sugar
  • glycotransferases are VERY specific for every aspect of the binding
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3
Q

What does glycosidases do?

A
  • Removes a specific sugar reisdues with the help of H20
  • Specific for the bond hydrolyzed
  • Important for
    • Producing final carbohydrate struture
    • degrading carb structures in lysosome
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4
Q

Describe a N-Linked glycoprotein

A
  • GlcNAc attached to a Asn
    • specific site: Asn-X-Thr/Ser
  • Common core: GlcNAc-GlcNAc-(mannose in triangle)
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5
Q

What is a dolichol and how is it used in glycoportein synthesis?

A
  • an isoprenoid compound with 16-20 isoprene units embedded in ER membrane
  • during the synthesis of N-linked glycoproteins it is attached to dolichol
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6
Q

How is a N-linked glycoprotein synthesized?

A
  • GlcNAc is attached to dolichol on cytoplasmic side of ER
  • Addictional glycosylation occurs then flipped to lumen of ER
  • 4 mannose and 3 glucoses added
  • Entire carbohydrate structure is transferred to Asn on a nascent protein
  • glucoses removed then put in vesicles to golgi
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7
Q

What is the final processing of a N-linked glycoprotein?

A
  • GlcNAc phosphate added
    • packaged in vesicles and merge with lysosomes
  • Trimming and addition of other sugars may occur goes through Golgi
    • Diverse final products
    • secreted or incorporated into membranes
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8
Q

Describe a O-linked Glycoprotein

A
  • GalNAc attached to either Ser/Thr
  • protein has to be assembled before it can be added
  • other types
    • O-mannosylation
    • O-fucosylation
    • Collagen: O-lined to 5-OH Lys
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9
Q

What is Type 1 Congenital Disorders of Glycosylation?

A
  • Most common
  • Problem occurs in the early steps in the synthesis of N-linked glycoproteins
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10
Q

What is type II congenital disorders of glycosylation?

A
  • Enzymatic defects in N-glycan processing enzymes
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11
Q

What is Walker-Warburg syndrome? and type of glycosylation disorder is it?

A
  • Walker is deficit in O-mannosyltransferase I
    • caueses alpha-dystroglycanopathies (congential muscular dystrophy)
  • example of O-linked glycosylation
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12
Q

What is the deficiency in a combined N- and O- glycosylation defect?

A
  • CMP-sialic acid transporter deficiency
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13
Q

What is lysosomal storage disease?

A
  • lysosomes contain exoglycosidases and endoglycosidases needed to break down glycoproteins and glycolipids
  • if the lysomes are not working correctly, incomplete degraded compounds accumulate in tissues and urine
  • results in hepatosplenomegaly, cataracts, and mental retardation
  • very rare usually autosomally recessive
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14
Q

What is I-cell disease (mucolipidosis II)?

A
  • defiency in GlcNAc-P glycosyltransferase
    • enzyme marks lysosomal proteins for their destination
  • lysosomal enzymes are instead secreted from cell and found in either the plasma or other body fluids
  • glycoproteins are not degraded and accumulate in enlarged lysosomes
  • severe psychomotor retardation, skeletal abnormalities, restricted joint movement, death by age 8
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15
Q

What are glycolipids built on mainly?

A
  • build on sphingosine
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16
Q

What is ceramide?

A
  • X is a H
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17
Q

What is a cerebroside?

A

If X is

  • a single monosaccharide (glucose or galactose)
  • most prevalent in neuronal cell membranes of brin
    • esstenial to myelin structure and function
  • occur in membranes of other tissues and is the precursor for most complex glycospingolipids
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18
Q

What is globoside?

A

If X

  • has multiple monosaccharides that are neurtal
  • Found in membranes of kidneys, RBCs, liver and spleen
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19
Q

What is a ganglioside?

A

If X is

  • sialic acid (NANA) is present
  • Most important Gm1, Gm2, Gm3
  • Act as
    • receptors for hormones and bacterial protein toxins
    • determinants for cell-cell recognition
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20
Q

What is a sulfatide?

A

If x

  • contains monosaccharidesulfates
  • important Myelin constituent, white matter
    • synthesized primary in oligodendrocytes
  • found in the membranes of kidney, spleen and retina
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21
Q

How is cerebroside synthesized?

A
  • made from ceramide
  • synthesized on luminal surface of the ER and then switched to cytosolic side of Golgi apparatus and reach plasma membrane through vesicle flow
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22
Q

How are globosides and gangliosides synthesized?

A
  • Synthesized by a series of specifc glycosyltransferases
  • UDP-Gal + glucocerebroside -> lactosyl ceramide
    • lactosyl ceramide is the precursor to both globosides and gangliosides
  • Glycosyltransferases add remaining hexoses
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23
Q

What is Tay-Sachs Disease?

A
  • Autosomal recessive defiency in hexoaminidase A
  • Ganglioside GM2 accumulates as shell-like inclusions in lysosomes. Looks like a milky halo occurs around the fovea of eye due to a build up ganglioside
  • red dot that develops in fovea is the result of the ganglion nerve death
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24
Q

What does glycocaylax with the microvilli?

A
  • glycocaylax provide the final stages of protein and carbohydrate breakdown for absorption
  • enzymes at the microvilli surface make sure the nutrients get absorbed immediately
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25
Q

How does the intestinal structure ensures max absorption?

A
  • Each villi receives blood supply and has blind ended leacteals from lymphatic system
  • Extensive blood supply ensures optimal removel of absorbed peptides , aa, sugars and fats
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26
Q

What is oral amylase?

A
  • 30-40% of starches being hydrolyzed to maltose
  • hydrolysis continues for up to hour in the stomach
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27
Q

What does pancreatic amylase digest?

A
  • maltose
  • maltotriose
  • alpha-limited dextrins
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28
Q

Where is the site of action of carbrohydrate enzymes?

A
  • enzymes located near the carrier of membrane transports that transports the free glucose or galactose into enterocyte
    • reduces the possibility of osmotic diarrhea
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29
Q

What splits lactose, sucrose, maltose and non-specific destrin?

A
  • lactase-lactose into glucose and galactose
  • Sucrase- sucrose into glucose and fructose
  • Maltase - maltose into glucose
  • alpha-dextrinase - non specific
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30
Q

How does glucose get into the blood from the intestine?

A
  • Active: Na+/glucose co-transporter SGLT1
  • Passive: glucose moves into the blood through GLUT2
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31
Q

What is lactose intolerance?

A
  • Develops from the lack of membrane bound enzymes resulting in malabsorption of carbohydrates
  • Undigested lactose causes osmolality changes
  • Test: overnight fasting followed by 50g of lactose in a 10% aqueous solution
    • low lactose tolerance curve or failure to blood glucose to rise
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32
Q

What are the sources of protein?

A
  • dietary protein
  • intestinal mucosa that is continually sleuthed off lumen ~50% of dietary protein
  • enzymatic proteins that are secreted into GI tract and are not used will be digested
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33
Q

How are pancreatic proteolytic enzymes activated?

A
  • Enterokinase is stimulated by the presence of trypsinogen
    • EK activates trypsinogen by releasing a hexapeptide from N-terminal
  • Active trypsin then autocatalytically to activate the bulk of trypsinogen and other peptidase
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34
Q

How do proteins enter the intestinal cell?

A
  • PEPT1
    • di and tripeptides are readily absorbed
    • coupled transport with Na+
  • various peptidases in cells break remaining linkages
  • protein meal: 40% free AA’s and 60% small peptides
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35
Q

What is celiac sprue?

A
  • a certain type of wheat protein attacks mircovilli of mucosa and removing it from the cells
  • patients are thought to lack certian peptidases and results in productin of toxic substances
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36
Q

What protein absorption disease is associated with cystic fibrosis and hereditary pancreatitis?

A
  • may lead to a decrease or absence of trypsin leading to poor absorption of protein
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37
Q

What protein absorption disease is associated with cystinuria?

A
  • Characterized by defective transport of cystine in proximal renal tubule and small bowel
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38
Q

What protein absorption disease is associated with Hartnup Disease?

A
  • Hereditary condition in which the active transport of several netural AAs is deficient in both the renal tubules and small bowel
  • when patients are fed dipeptides these are readily absorbed, just not free AAs
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39
Q

What property is important for digestion and absorption of lipids?

A
  • insolubility of lipids in water are important properties for the digestion and absorption of lipids
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40
Q

What is the process of absorption on 4 major events?

A
  • Secretion of bile and various lipases
  • Emulsification
  • Enzymatic hydrolysis of ester linkages
  • Solubilization of lipolytic products within bile salt micelles
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41
Q

What is lipase?

A
  • water-soluble enzyme that only acts on the triglyceride droplet surface
  • produces monoglycerides and fatty acids
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42
Q

What are micelles and how are they used?

A
  • essentially small aggregates of mixed lipids and bile acids suspended within ingesta
  • micelles bump into brush border of enterocytes and monoglyceride and FA are taken up into epithelial cell
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43
Q

How do lipids enter the blood?

A
  • After the FA and monoglycerol enters thecell, triglycerides reassemble along with cholesterol and cholesterol ester and are packaged into lipoproteins
  • intestine produces chylomicrons
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44
Q

What are the fat soluble vitamins?

A
  • Vitamins A, D3, E and K
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45
Q

What is the source of vitamin A?

A
  • from animal sources or from beta-carotene
    • one molecule of beta-carotene makes vitamin A
  • becomes water soluble by micellar solubilization and absorbed by small intestine passively
  • converted to retinyl ester, made into chylomicrons and eventually taken by liver
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46
Q

What is the source of Vitamin D3?

A
  • Cholecalciferl from either milk or formed in sun exposed skin
  • similar absorption mechanism to vitamin A
  • Vitamin D3 is transferred to a vitamin D binding protein in plasma and stored in various organs
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47
Q

What is the source of Vitamin E?

A
  • derived from vegetable oils by passive diffusion
  • transported in circulation associated with lipoproteins and erythrocytes
    • helps protect membranes and RBCs from free radical damage
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48
Q

What is the source of vitamin K?

A
  • derived from green vegetables or gut flora
  • phylloquinones from veggies is absorbed passively
  • menaquinones from gut flora are taken up passively
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49
Q

What are the water soluble vitamins?

A
  • Vitamin C actively taken up in ileum
  • B1 at low concs are actively uptaken but higher cons areby passive diffusion
  • B2 by specific, saturable, active in small intestine
  • B6 simple diffusion
  • Folic acid
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50
Q

How is water and electrolyte absorbed?

A
  • Active Na+ transport, which passively draws along anions and water
  • increased effectiveness in absorbing ions along GI tract because the decreased premeability to ions to prevent back flow
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51
Q

How is Ca2+ absorbed?

A
  • proximal intestine
  • pathway
    • entry at brush border
    • regulation of intracellular Ca2+
    • Ca2+ exits basolateral side
      • Ca2+ ATPase
      • 1,25-dydroxyvitamin D3 sensitive
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52
Q

How is iron absorbed?

A
  • Heme absorbed by endocytosis and digested by lysoenzymes to release iron
  • Non-heme iron
    • enterocytes of proximal small intestine release transferrin that binds iron in lumen
    • transferrin-iron is absorbed at brush border by specifc transporters
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53
Q

What is hemochromotosis?

A
  • unregulated iron absorption leading to overload
  • leads to
    • cirrhosis
    • diabetes
    • cardiomyopathy
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54
Q

What kind of pathologies can be identified with plain film?

A
  • acute and chronic, diffuse or localized abdominal pain
  • obstructing voiding symptoms
  • renal calcuili
  • search for foreign bodies
  • evaluation of pneumperitoneum, congential abnormalities
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55
Q

What is the bony inspection?

A
  • Lower rib cage
  • lumbar spine
  • sacrum
  • pelvis
  • hip joings
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56
Q

How do you read abdominal plain films?

A
  • Projection of film: PA, AP (most are)
  • View: supine, erect, lateral decubitus
  • Exposure: spine visible?
  • Solid organs
  • Hollow organs
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57
Q

What is the structure of the ABO blood system?

A
  • complex polysaccharides
  • Same backbone but different antigens
    • sphingolipids
    • glycoproteins
  • H antigen is the precursor to all
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58
Q

What does a N-acetylgalactosamine glycosyltransferase?

A
  • coded by A allele
  • Adds a GalNAc to the terminal Gal in a alpha-1,3 linkage
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59
Q

What does galactosyltransferase do?

A
  • coded by B allele
  • Gal is added to terminal Gal in alpha-1,3 linkage
60
Q

What does the O allele code for in the ABO blood system?

A
  • codes for an inactive protein
  • O group has neither of these monosaccharides at terminus antigen
61
Q

What is the Lewis blood group system?

A
  • H gene in epithelial and secretory tissues but detected in blood
  • either glycoproteins or spingolipids
  • fucosyltransferase
    • FUT1-RBC
    • FUT2-epithelial and secretory tissues
      • FUT3- epithelial and secretory tissues but adds a fucose to GlcNAc in a1,3 or a1,4
62
Q

Describe a GPI

A
  • structure
    • phosphoethanolamine binds to C terminus of protein
    • core tetrasaccharids
    • phosphatidylinositol with 2 FA in membrane
  • binds proteins and concentrates them in lipid rafts
    • phospholipase will cleave the anchor from the membrane and release the protein
63
Q

Where does the synthesis of GPI anchors occur?

A
  • occurs at first the exterior and then interior of ER
    • Exterior GlcNAc is added then flipped to the lumen
  • proteins end up on exterior of plasma membrane
64
Q

Describe GAGs

A
  • long and unbranched heteropolysaccharides
    • highly charged so protein ligands can bind electrostaticlly
  • disaccharid repeating units
  • sulfate groups
65
Q

Where are GAGs located and why are they so good in that environment?

A
  • found in extracellular space in ground substance, gel-like consisteny
  • Physical properties
    • not easily compressed - ideal for joints
    • negatively charged and attracts Na+ and K+ ions which absorbs water
    • maintains fluid and electrolyte within tissues
66
Q

Describe Hyaluronate

A
  • D-glucuronic acid + GlcNAc
    • beta 1,3
    • units beta 1,4
  • can be huge
  • not sulfated
  • not covalently bound to protein
67
Q

Describe chondroitin sulfates

A
  • D-Glucuronic acid + GalNAc
    • b1,3
    • B1,4 links
  • sulfated
    • O of C4 of GalNAc (chondroitin-4-sulfate)
    • O of C6 of GalNAc (chondroitin-6-sulfate)
68
Q

Describe Dermatain Sulfate

A
  • L-uduroincid acid + GalNAc
    • B1,3
    • B1,4 unit link
69
Q

Describe Heparin

A
  • D-glucuronic acid +glucosamine
    • B1,4
    • a1,4 unit links
  • varibly sulfated
    • glucoasamine may sulfated or acetylated
  • most negatively charged polyelectrolyte
    • found exclusively only in granules of mast cells
70
Q

How is Heparin used as a anticoagulant?

A
  • Heparin binds to Antithrombin III (AT)
    • AT activated, increases rate by 1000x when compared AT activation w/o heparin
  • AT inactivates trombin and other clotting proteases
71
Q

Describe Heparan Sulfate

A
  • same as heparin
    • Dglucuronic acid (or L-iduronic acid) + glucosamine
    • B1,4
    • a1,4
  • exceptions
    • increased N-acetyl groups
    • decreased N-sulfate groups
    • decreased O-sulfate groups
    • more varibale composition
72
Q

Describe Keratan sulfate

A
  • Gal + GlcNAc
    • B1,3
    • B1,4 repeating unit
  • two types of sulfate content
    • Keratan sulfate I (cornea) - protein linked via GlcNAc-Asn bond
    • Keratan sulfate II (cartilage) - linked to protein via GalNAc-Ser/Thr bond
73
Q

How are GAGs synthesized?

A
  • GAG chains asembled in Golgi on intact proteins
  • synthesis
    • tetrasaccharide core attached to protein by glycosyltransfereases
    • repeated
      • GalNAc transferease
      • GluUA transferase
    • Sulfation happens as the chain grows
74
Q

What are proteoglycans?

A
  • large molcule with GAGs (can be more than 1 type) and protein core
  • main part of ground substance
    • negatively charged to attract ions and water
75
Q

What is aggrecan proteoglycan?

A
  • proteoglycan expressed in chondrocytes (healthy cartildge)
  • core protein binds many sacchrides in 3 regions
    • inner (N terminus)- N linked carb structures
    • Central - O linked carbs and binds GAGs via Ser/Thr
    • Outer - chondroitin sulfate
76
Q

What is monopolysaccharidoses?

A
  • proteoglycans are degraded by sequential actions of lysosomal enzymes
  • symptoms
    • skeletal abnormailites
    • metal retardation
    • psychomotor regression
77
Q

How are GAGs regulated?

A
  • controlled at the level of hexoasmine synthesis
  • controlled at step that produces glucosamine
  • regulatory step: UDP-glucose DeH
    • UDP-glucose -> UDP-GlcUA
    • inhibited by UDP-xylose
78
Q

What are the 4 pathways of lipid transport?

A
  • Food -> any tissue
  • Liver -> other tissues
  • Other tissues -> liver
  • Adipose tissue -> other tissues
79
Q

How are lipids basically transported?

A
  • large molecular assemblies of protein and lipids
  • protein - apolipoportein
  • lipid- TAGs, FFA, cholesterol, cholesterol esters, phospholipids
  • chylomicrons move into the lymph and then enter the bloodstream via the left subclavian vein
    • chylomicrons have ApoB48
80
Q

How do lipids get from food to other tissues?

A
  • Bile salts emulsify fats
  • intestinal lipases degrade TAGs
    • FA and other breakdown products are absorbed into mucosa and reassembled into TAGs
  • TAGs, cholesterol, and apolipoproteins are assembled into chylomicrons
    • chylomicron sent into bloodstream
  • Lipoprotein lipase activated by apoC-II and convertags TAGs into FA and glycerols
    • FA and glycerol enter cell and either oxidized for fule or reassembled to TAGs for storage
81
Q

What is the role of apolipoproteins?

A
  • Regulate plasma lipid metabolizing enzymes
    • activate Lipoprotein lipase
  • Facilitate lipid transfer
  • Mediate endocytosis

Chylomicrons get more Apos from HDLs

82
Q

What does ApoE do?

A
  • Apolipoprotein required to mediate hepatocyte receptor endocytosis
  • Occurs after chylomircon has delivered its TAGs to tissues and is now smaller and composed of cholesterol and cholesterol esters
83
Q

How do lipoproteins get transported from liver to other tissues?

A
  • extra carbohydrates and fats in liver and used to make FA to assemble TAGs and lipids
    • assembled in VLDLs (ER and Golgi)
  • VLDL are exocytosed directly into blood
84
Q

Describe VLDLs

A
  • once VLDLs enter blood they quickly get more ApoC and ApoE from HDL
    • Cholesterol ester transfer protein (CETP) - VLDLs get more CE from HDL
  • Short lifespan <1hr
  • has ApoB100
85
Q

What is the fate of VLDL remants?

A
  • larger ones that have lots of apoE are endocytosed by liver
  • smaller ones become IDLs then LDLs
    • become LDLs by hepatic lipase
    • apoE leaves and LDL will be endocytosized by tissues/liver
86
Q

What are the properties of LDLs?

A
  • ~40% CE and 20% phospholipids
  • Only carry apoB-100
    • 2/3 able to be endocytozied by hepatocytes to be degrade
    • 1/3 induces ACAT to create CEs for storage and inhibits HMG-CoA reductase. Also reduces LDL receptors
  • 3 day lifespan
87
Q

What happens to the LDLs that are not cleared by LDL receptor?

A
  • Macrophages and some endothelial cells (spleen and intestines) have scavenger receptors
    • look for old LDLs
88
Q

How do lipids get from other tissues to liver?

A
  • ApoE mediated endocytosis of remnant particles containing CE (obtained from HDLs mediated by CETP)
  • CE is selectively transferred to hepatocytes via SR-B1
  • endocytosis of large HDLs with ApoEs
89
Q

Describe HDLs

A
  • Rich in phospholids released by liver and small intestine
    • looks like a disc
  • HDLs are converted into spherical lipoportein particles by accumulating cholesterol and CEs
  • dock on cell surface through apoA-I or apoE
90
Q

What does ABC1 do?

A
  • ATP-binding cassette protein-1
  • located in cell membrane and pumps free cholesterol from cell surface into HDL
91
Q

What does LCAT do?

A
  • Lechithin-cholesterol acyl-transferase
  • soluble protein made by liver
  • binds to surface of HDL and is activated by apoA-1
  • catalyzes the esterfication of cholesterol
92
Q

What is the fundamental difference in cholesterol delivery between LDL and HDL to hapatocytes?

A
  • During cholestrol transport via LDLs, LDL + C+ CE are endocytosed in one piece
  • HDL remains intact but gives off CEs to hepatocytes
    • very few HDL acquire enough apoE to be endocytosed
93
Q

What occurs in A-betalipoproteinemia?

A
  • Deficient in TAGs transfer protein in ER
    • no ApoB lipoprteins are assembled (chylomicrons, VLDLs, LDLs)
  • rare, severe fat malabsorption
  • TAG accumulation in intestinal mucosa and liver
94
Q

Describe Tangier disease

A
  • Absence of ABC1 protein
    • apoA cant get lipids and mature HDls dont form
  • Deposit of CE in reticuloendothelial cells, bone marrow, Schwann cells
  • tonsils are orange
95
Q

What is ApoCIII deficiency?

A
  • absence of ApoCIII inhibits Lipoprotein lipase that decreases plasma TAGs and LDL while increasing plasma HDLs
  • found in Amish and ashkenazi jewish populations
96
Q

What is CETP deficiency?

A
  • CE cant be transferred to othe remnants
  • Benign condition
  • LDL is normal to lo
  • HDL is elevated
97
Q

How do lipids transport from adipose to other tissues?

A
  • TAGs are converted to FA and sent out to the blood
  • pyruate is converted at first very similar to gluconeogenesis but PEP is converted to glycerol 3-phospahte and made into TAG
98
Q

How is the mucosal afferent endings stimulated?

A
  • Stimulated by 5-HT (serotonin) released by EC cells in intestinal mucosa as the result of chemical and mechanical stimulation
  • creates a generator potetial
    • size of potential depends on the strength of stimulus\
  • Stimulates
    • Extrinsic (vagal and spinal afferents)
    • Intrinsic (IPANs)
99
Q

What are the three pathways that connect the gut to the CNS?

A
  • vagal affarents from upper GI
  • pelvic afferents from colorectal
  • splanchnic afferrents from entire GI, mainly nociceptive
100
Q

What are nociceptive fibers?

A
  • splanchnic/spinal afferents that sense pain but vagal nerves stimulation doesnt produce pain
    • slow, unmyelinated C fibers
    • pain is felt as a dull ach and hard to locate
  • activated by STRONG distortion or contraction of bowel wall
101
Q

What do vagal and pelvic afferents do?

A
  • Afferents regulate visceral tone, distension, motility and secretion
102
Q

What do IMAs do?

A
  • forms ending in either longitudinal and circular muscle layers or in myenteric plexus
  • Activated by stretch, distension, and contraction
103
Q

What do IGLE’s do?

A
  • Nerve endings are in contact with CT casule and enteric glial cells surrounding myenteric ganglia
  • Detect shearing forces between orthogonal muscle layers
104
Q

How much stimulus is need to activate vagal and splanchinc afferents?

A
  • Vagal - often need lowerlevels of distension to be activated
  • Splanchnics - often need a strong stimulus to be activated
105
Q

What are IPANs?

A
  • multipolar and their terminal are confined to the wall of the intestine near the plexuses
  • involved in motility, secretion, and vasodilation within intestine
  • when exicted it will release 5-HT
106
Q

Where are cell bodies of vagal afferents located?

A
  • nearly all parasympathetic afferents return and synapse onto nucleus tractus solitarius (NST)
    • cells bodies of neurons sit just ouside the CNS in nodose ganglion
    • NST receives info about BP, CO levels, and gut distension
107
Q

What do IVAs do?

A
  • free nerve endings that termina in the mucosa
    • have a low threshold
  • respond to mechanical stimuli applied to villi and detect material that is absorbed
108
Q

Why is serotonin important in the gut?

A
  • released by EC cells as the result of mechnical or chemical stimulation
  • 5-HT activates IPANs that activates ascedning excitatory and inhibits descending
  • SERT uptakes 5-HT from synaptic cleft to terminate serotonin action
    • not all absorbed some escapes to blood to be stored in platelets and used to vasocontrict during clotting
109
Q

What occurs during vomiting?

A
  • Sympathetic - sweating, pallor, increased respiration, and HR and dilation of pupils
  • Parasympathetic - profuse salvation, pronounced motility of esophagus, stomach and duodenum, relaxation of sphnincters
  • vomiting is coordinated in vomiting center in brain stem
    • chemo can also activate vomiting center
110
Q

What can occur during visceral hypersensitivity?

A
  • may be the result of an ulcer or gastric distension by causing sensory neurons to be more sensitive
  • nocipceptors can be damaged
    • damage can cause them to fire randomly without a stimulus
111
Q

Define hyperalgesia

A
  • exaggerated pain in response to a painful stimulus
112
Q

Define allodynia

A
113
Q
  • pain from a stimulus that usually doesnt cause pain
A
114
Q

How can inflammation affect nociceptive fibers?

A
  • when damage cells release their cellular contents, their prescence can cause the secretion of other molecules and dilation of blood vessels
  • bradykinin, histamine, and prostaglandins trigger action potentials in nociceptive fibers
  • lysed cells will release large amounts of K+ which is related to the degree of pain expieranced
115
Q

What is a sensory TRP channel?

A
  • sense distinct thermal thresholds from very hot to cold
  • each thermo-TRP is activated by a specific natural compounds and synthetic substances
116
Q

Irritable bowel syndrome

A
  • associated with strong contrctile activity of gut
    • doesnt lead to other health problems
  • increased gut awareness is due to visceral afferent nerves being hypersensitive and increased 5-HT release from gut mucosa
117
Q

What is Crohns disease?

A
  • formation of patchy inflammation (cobblestone) mostly in small intestine but can be located in other GI locations
  • extends to all tissue layers
  • symptoms
    • abdominal pain, vomiting, diarrhea, blood in stool, fatigue, weight loss, growth failure
118
Q

What is ulcerative colitis?

A
  • limited to large intestine and inflamed area can vary from patient to patient
  • symptoms
    • bloody, diarrhea, abdominal cramping, and fealing of urgency or little warning when they have a bowel movement
119
Q

How is gut pain treated?

A
  • opiods are used to manage severe diarrhea and control high output ostomies
  • loperamind, diphenoxylate, and difenoxin only opioid derivatives approved to treat diarrhea
120
Q

What are the four major forms of single gene hypercholesterolemia?

A
  • LDLR
    • loss of function mutations autosomal dominant
  • APOB
    • receptor binding site mutations autosomal dominant
  • PCSK9
    • gain of function-enhanced activity, autosomal dominant
  • LDLRAP1
    • loss of function, autosomal recessive, overall rare
121
Q

What are the symptoms of familial hypercholesterolemia?

A
  • angina
  • buildup of cholesterol in tissues
  • calves camping
  • stroke-like symptoms
  • sores on toes that doenst heal
122
Q

What happens with LDL-R gene deletion?

A
  • loss of function mutation
    • occurs in low density lipoprotein receptor in liver
  • Test detects 99% of mutation in LDL-R and PCSK-9 genes
    • 80% of mutations in APOB Exon 26
123
Q

Describe ApoB binding mutations

A
  • Normally ApoB facilitates receptor-mediated endocytosis
  • endosome fuses with lysosome
    • removes aa and FA
    • creates cholesterol ester droplet
124
Q

What occurs in a PCSK9 mutation?

A
  • gain of function
  • typically LDL receptor is part of the internalisation of the LDL then recycled
  • Mutation causes PCSK to bind to LDL-R and be internalized
    • no dissociation, degradation of LDLR in lysosomes
125
Q

What occurs because of LDLRAP1 mutation?

A
  • loss of function, autosomal recessive
  • LDL receptor adaptor protein is required for LDL receptor binding to clathrin
    • losses this adaptor protein
126
Q

What is the mechanism of action of statins?

A
  • inhibit HMG-CoA reducatse
  • mainly inhibit enzyme in liver
    • reduces circulating LDL because it causes the hepatocyte to upregulate LDL-R expression since it cant make cholesterol
  • Activates SREBP
127
Q

What is the mechanism of action of fibrates?

A
  • Fibrates bind to nuclear receptor PPAR-alpha
    • Fibrate increases HDL levels and decreases TAG levels
    • Decreases VLDL
  • Receptor works as a transcription factor to change gene expression in target cells
128
Q

What is a mechanism of action of Niacin?

A
  • at high doses, niacin increases HDL levels and decreases TAGs adn LDL levels
  • mechanism is not completely clear
    • niacin thought to inhibit TAG synthesis enzyme, decreasing VLDL production
129
Q

What is the mechanism of action of Ezetimibe?

A
  • inhibits cholesterol absorption in small intestine
    • reduces absorption of dietary cholesterol and promotes cholesterol excretion
130
Q

How does adipose tissue buffer dietary fat?

A
  • buffer daily influx fat
  • obesity leads to enlarged adipocytes which decreases lipid buffering capacity
  • when not functioning properly, other tissues are exposed to excess FA and TAGs
    • interferes with insulin sensitivity (skeletal muscle and liver) and insulin secretion (pancreas)
131
Q

What role do macrophages in obesity?

A
  • macrophages in adipose tissue are a hallmark of inflammation in obesity
  • adipose cells die because they become necrotic and dont function
132
Q

What does thiazolidinediones do?

A
  • PPAR-y activator, insulin sensitizer
  • induces the differentiation of preadipocytes (stem cells) into small, young active adipocytes
133
Q

Why is glucose important to adipose cells?

A
  • glucose is converted into Glycerol-3P
  • Fatty acyl CoA will combine with G3P to make TAGs
    • adipose cells have no way to make glycerol because they lack glycerol kinase
134
Q

How does insulin resistance affect adipose cells?

A
  • insulin regulates lipoprotein lipase and glucose transport
    • low insulin inhibits both of there actions
  • leads to improper chylomicron degradation
135
Q

What are the common features of all glycoproteins?

A
  • most common posttranslational modification
  • almost all secreted
    • lysomosal and membrane associted
    • almost never are in the cytoplasm
  • synthesized on rER via secretory pathway and go through the Golgi
  • can have alot of heterogenity
136
Q

What is a mucin?

A
  • O-linked glycoprotein
  • can form gels that lubricate, provide chemical barriers and hold water
    • very negative structure
    • pulls in ions and water
  • structure
    • middle part has 50% of Ser or Thr that is glycosylated
  • mucins are increased in many cancers, asthma, bronchitis, COPD and cystic fibrosis
137
Q

What does ApoA do?

A
  • cofactor for “LCAT”, chlyomicrons, HDL
138
Q

Function of ApoB48?

A
  • help Chlyomicrons remants return remants to liver
139
Q

Function of ApoB100?

A
  • on VLDL, IDLs and LDL
  • binds to LDL receptor
140
Q

Function of ApoCII?

A
  • on chylomicrons, VLDL, HDL
  • activate binding to Lipoprotein lipase to cleave TAGs
141
Q

What is the function of ApoE

A
  • activates reuptake with liver
  • on everything except LDL
142
Q

Function of LCAT

A
  • Converts cholesterol to CE
  • allows membranes to accept more cholesterol
143
Q

Function of CETP

A
  • moves CE to LDL and LDL
144
Q

Function of hepatic liapse

A
  • on liver cells to acquire TAGs from IDL to convert it to LDL
145
Q
A

Block 3 (8 decks)

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