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    Parte integrante da Disciplina MED7002

    Introduo ao estudo da Medicina II

    Profa. Dra. Cristina Maria Henrique Pinto

    Profa. Associada II do Depto. Cincias Fisiolgicas-CCB-UFSC

    Como citar este documento: PINTO, Cristina Maria Henrique. Fisiologia do SistemaDigestrio. Disponvel em: . Acesso em: (coloque a

    data aqui)

    Fisiologia doSistema

    Digestrio

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    Fisiologia doSistema

    DigestrioEsta uma apresentao dos principaisslides utilizados em minhas aulas tericas

    para a graduao em Medicina (2 fase).

    Bons estudos!

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    Esta aula e outros materiais relacionados estodisponveis nas pginas dedicadas MED da 2 fase em meu website:

    www.cristina.prof.ufsc.br

    porm o acesso restrito e exige senha e login, divulgadosnoMoodle da UFSC!

    Veja aqui a bibliografia bsica

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    Digesto e absoro dos

    principais nutrientes,gua, eletrlitos e

    vitaminas constituintes

    de uma dieta ideal

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    Caractersticas do Intestino Delgado:adaptaes morfofuncionais para a digesto e absoro

    Adaptaes damucosa intestinal

    (pregas, vilosidades e

    microvilosidades)amplificam a

    superfcie de contato

    entre o epitlioabsortivo do intestino

    delgado e os

    nutrientes.

    Vilosidades dointestino delgado

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    vilos

    microvilos

    Caractersticas do Intestino Delgado:adaptaes morfofuncionais para a digesto e absoro

    Pregas,vilosidades e

    microvilosidades

    multiplicamem 600 vzes

    a superfcie

    absortivae digestiva do

    intestino delgado

    pregascirculares

    rea total do intestino delgado de humanos:200m2 (*)

    equivalente rea de uma quadra de tnis!!!

    (*) Voc acha pouco? Ento, com a ajuda de um liquidificador, triture o seu almoode hoje (no esquea dos lquidos e da sobremesa) at que este torne-se

    pastoso. Ento, com a ajuda de um rdo, espalhe-o por toda a superfcie de uma

    quadra de tnis... Agora talvez voc tenha uma melhor noo da dimenso da

    superfcie absortiva do intestino delgado...

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    This is a low power image of the first part of

    the Small Intestines, the Duodenum. It alsohas the basic layers of the GI system like the

    Mucosa, (blue arrows) , Submucosa, (redarrows), and the Muscularis Externa (green

    arrows). The small intestines has manyadaptations to increase it's surface area a. First

    it has Plicae Circulares (valves of kerckring),which are extensions of thesubmucosa, indicated by the yellow arrow.The next adaptation is the Villi, which are

    extensions of the mucosa indicated by the blackarrows. Of important identification clues about

    the duodenum is the presence of Brunner'sGlands which are very abundant in thesubmucosa. No other part of the intestines has

    these glands so once you see these you can be

    sure you are looking at the duodenum.

    extrado, enquanto disponvel, de: http://www3.umdnj.edu/histsweb/lab20/lab20duodenum.html

    Caractersticas do Intestino DelgadoDuodeno

    http://faculty.une.edu/com/abell/histo/histolab3d.htm

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    INTESTINO DELGADO E AS ADAPTAES ABSORTIVAS

    http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/smallgut/anatomy.html

    The panels below depict the bulk of this surface area expansion, showing villi, epithelial

    cells that cover the villi and the microvilli of the epithelial cells. Note in the middle panel, a

    light micrograph, that the microvilli are visible and look something like a brush. For this

    reason, the microvillus border of intestinal epithelial cells is referred to as the "brushborder".

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    Caractersticas do Intestino Delgado:adaptaes morfofuncionais para a digesto e absoro

    http://www.mc.vanderbilt.edu/histology/

    Existncia de uma densarede de capilares,

    vnulas e ductos lacteais

    que permeiam os vilos

    intestinais, permitindo,

    assim, o aporte de

    substncias e a

    drenagem dos nutrientes,gua e eletrlitos

    absorvidos pelo epitlio

    intestinal.

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    Overall fluid balance in the human gastrointestinal tract. About 2 L of water is ingested each day, and 7 L of various secretions entersthe gastrointestinal tract. Of this total of 9 L, 8.5 L is absorbed in the small intestine. About 500 ml is passed on to the colon, whichnormally absorbs 80% to 90% of the water presented to it. (From Vander AJ, Sherman JH, Luciano DS: Human physiology, ed 6,New York, 1994, McGraw-Hill.) Levy et al., 2006

    VOLUMES DIRIOS

    INGERIDOS,SECRETADOS,ABSORVIDOS E

    EXCRETADOS PELOTGI

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    Structure of a branched starch molecule and the action of -amylase. The colored circles represent glucose monomers linked

    by -1,4 linkages.T

    he black circles represent glucose units linked by -1,6 linkages at the branch points.T

    he -1,6 linkagesand terminal -1,4 bonds cannot be cleaved by -amylase. Berne et al., 2004

    Digesto do amido (amilopectina)~glicognio

    Digesto e absoro decarboidratos

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    Digesto final de polissacardeos pelas enzimas da borda-em-escova(constitucionais) do intestino delgado

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    Functions of the major brush border oligosaccharidases. The glucose, galactose, and fructose molecules released by enzymatic hydrolysis are then

    transported into the epithelial cell by specific transport proteins. The glucose-galactose transporter is also known as SGLT1 and the fructose transporteras GLUT5. G, Glucose; Ga, galactose; F, fructose. Berne et al., 2004

    Amidoglicognio

    Digesto e absoro dos derivados da digestodo amido (amilopectina) ~ glicognio

    enzimas e transportadores presentes nos microvilos (borda-em-escova)

    (SGLT1)

    salivar epancretica

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    Fig. 33-2 Functions of the major brush border oligosaccharidases. The glucose, galactose, and fructose molecules released by enzymatic

    hydrolysis are then transported into the epithelial cell by specific transport proteins. The glucose-galactose transporter is also known asSGLT1 and the fructose transporter as GLUT5. G, Glucose; Ga, galactose; F, fructose. Berne et al., 2004

    (SGLT1)

    SacaroseLactose

    Amidoglicognio

    Digesto e absoro de dissacardeos da dietaLACTOSE e SACAROSE

    enzimas e transportadores presentes nos microvilos (borda-em-escova)

    salivar epancretica

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    Absoro de glicose/galactose nas microvilosidades (borda-em-escova) do intestino delgado

    http://faculty.uca.edu/~johnc/trans1440.htm

    veja animao onl-ine: http://www.stolaf.edu/people/giannini

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    Digesto de protenas e absoro depolipeptdeos e aminocidos

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    Incio da digesto das protenas:estmago (pepsina)

    extrado de: Digestive System (Vander, Sherman & Luciano, 2002 Human Physiology, chap. 17, McGraw-Hilll)

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    extrado de:Digestive System (Saladin, 2002 Anatomy and Physiology, chap. 25, McGraw-Hill)

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    extrado de:Digestive System (Saladin, 2002 Anatomy and Physiology, chap. 25, McGraw-Hill)

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    extrado de:Digestive System (Saladin, 2002 Anatomy and Physiology, chap. 25, McGraw-Hill)

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    Digesto final de polipeptdeos pelas enzimas da borda-em-escova(constitucionais) do intestino delgado

    extrado de: Digestive System (Vander, Sherman & Luciano, 2002 Human Physiology, chap. 17, McGraw-Hilll)

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    Fig. 33-6 The hierarchy of proteases and peptidases that functions in the small intestine. The pancreatic proteases convert dietary proteins tooligopeptides. Brush border peptidases then convert the oligopeptides to amino acids (about 70%) and dipeptides and tripeptides (about 30%). The amino

    acids are taken up across the brush border membrane by amino acid transporters and the small peptides by a peptide transporter. In the cytosol of theenterocyte, dipeptides and tripeptides are cleaved to single amino acids. (From Van Dyke RW: Mechanisms of digestion and absorption of food. InSleisenger MH, Fordtran JS, editors: Gastrointestinal disease, ed 4, Philadelphia, 1989, WB Saunders.) Berne et al., 2004

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    Fig. 33-7A wide variety of dipeptides and tripeptides is taken up across the brush border plasma membrane by a single type of H +-powered secondaryactive transport protein. The H+ gradient is created by Na+-H+ exchangers in the brush border membrane. In the epithelial cell cytosol, peptidases cleavemost of the dipeptides and tripeptides to single amino acids, which leave the cell at the basolateral membrane by facilitated transport. Berne et al., 2004

    Digesto e absoro de polipeptdeos eaminocidos (entercitos)

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    Digesto e absoro de gorduras

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    TG

    BOCAESTMAGO

    INTESTINO DELGADO mucosa ID linfa

    TG sais biliares(fgado)

    Lipase(PAN)

    ChlFlp

    TG:TriglicerdeosChl:colesterolFlp:fosfolipdeos

    MG AGL

    QUIL

    OMCRO

    NS

    MG: monoglicerdeosAGL: c.graxoslivres

    Flp(8%)

    Apoprotena B

    (2%)

    Chl(2%)

    88%+

    Chl Flp

    MICELA

    sais biliares

    RER

    Resumo da digesto e absoro de gorduras

    Cristina, 1999 modificado de Johnson, 1999

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    MICELAsais biliares

    TGLipasepancretica

    MG AGL Glicerol

    Fgado

    leo

    Chl

    Flp

    Quilomcrons

    vasos

    lacte

    ais

    (lin

    fa)

    capilares

    RER

    Digesto e absoro de triglicerdeos

    Cristina, 1999 modificado de Johnson, 1999

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    Vander, Sherman & Luciano, 1997

    MIC

    ELA

    Sais biliares e a emulsificao das gorduras:a formao das micelas para a digesto pela lipase pancretica

    extrado de: Digestive System (Vander, Sherman & Luciano, 2002 Human Physiology, chap. 17, McGraw-Hilll)

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    Lipid absorption in the small intestine. Mixed micelles of bile acids and lipid digestion products diffuse through the unstirred layer and among the microvilli.As digestion products are absorbed from free solution by the enterocytes, more digestion products partition out of the micelles. The ability of micelles to

    diffuse among the microvilli makes the whole surface of the brush border available for lipid absorption.Transport proteins mediate the facilitated transport

    of fatty acids and cholesterol across the brush border plasma membrane. In the cytosol of the epithelial cell, fatty acids are bound to fatty acid-bindingprotein and cholesterol is bound to sterol carrier proteins. Berne et al., 2004

    Digesto eabsoro detriglicerdeos

    camada estacionriade gua (dificultaadifusodoslipdeosato epitlioabsortivo)

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    http://www.medscape.com/viewarticle/416521_4

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    http://www.medscape.com/viewarticle/416521_4

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    An outline ofthe major metabolicpathways bywhichchylomicronremnantsandlow-densitylipoprotein (LDL)are formedfromchylomicronsandvery-low-

    densitylipoprotein (VLDL),respectively,andsubsequentlycatabolised. High-densitylipoprotein (HDL)issecreted bythe gutandliverand receivesadditionalcomponentsduringthemetabolism oftriglyceride-richlipoproteins.IDL,intermediate-

    densitylipoprotein; apo,apolipoprotein; TG,triglyceride;CE,cholesteryl ester; CETP,cholesteryl estertransferprotein;SR,scavenger receptor; LCAT,lecithin:cholesterolacyltransferase.Adaptedwithpermission from Durrington PN.

    Hyperlipidaemia: Diagnosis andManagement. 2nd edition.London:Butterworth-Heinemann; 1995.http://www.cmglinks.com/asa/lectures/Part_2/lecture/2.htmhome:http://www.cmglinks.com/asa/lectures/

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    The oil-drop or mixed micelle model of lipoprotein structure forchylomicron, very low-density lipoprotein (VLDL), low-densitylipoprotein (LDL) and high-density lipoprotein (HDL). Apolipoproteins in the outer phospholipid membrane are designated byletters. The major differences between the different lipoproteins are in 1) the size of the neutral lipid (triglyceride and esterifiedcholesterol) core; 2) the lipid composition in the core; and 3) the apolipoprotein composition. Although not shown, unesterifiedcholesterol is found predominantly in the phospholipid monolayer. Adapted with permission from Oberman A, Kreisburg RA,Henkin Y (editors).Principles and Management of LipidDisorders. Baltimore: Williams & Wilkins; 1992;87-105.

    http://www.cmglinks.com/asa/lectures/Part_2/slides/3.htm

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    (...) Contedo abdominal de coiote, sendo as linhas finas esbranquiadas (setas) os ductos linfticos preenchidos porquilomcrons sintetizados pelos entercitos (intestino delgado). Quando grandes quantidades de quilomcrons esto sendoabsorvidas, a drenagem linftica do intestino delgado parece leitosa e os ductos linfticos so visveis (setas). Esta linfa passa

    atravs de ndulos linfticos mesentricos (LN) e da, para linfticos maiores (...)http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/absorb_lipids.html

    Drenagem linftica intestinal de quilomcrons no perodops-prandial

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    Mucosa em repouso Absoro de NaCl ativada

    Mecanismos absortivos do epitlio do intestino delgadogua e NaCl

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    Mecanismos absortivos do epitlio do intestino delgadogua e NaCl

    Movimento de gua Viso integrada

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    Mecanismos absortivos do epitlio do intestino delgado

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    Mecanismosabsortivos do

    epitlio do

    intestinodelgado

    extrado, enquanto disponvel (at 2006) de: http://medweb.bham.ac.uk/research/toescu/Teaching/GIT2ndYBIOCHEM.html

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    Mecanismosabsortivos do

    epitlio dointestino delgado

    NOTES

    1. The H available for

    exchange with Na comes

    from the dissociation of

    H2CO3 formed followingthe diffusion of CO2 from

    lumen. The formation of

    H2CO3 is catalysed by

    Carbonic anhydrase (not

    shown) .

    2. The bicarbonate (HCO3-)

    imbalance resulting fromthe exit of H ions is

    counteracted by the

    activity of a baso-lateral

    HCO3/Cl exchange

    system

    extrado, enquanto disponvel (at 20076) de: http://medweb.bham.ac.uk/research/toescu/Teaching/GIT2ndYBIOCHEM.html

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    Mecanismosabsortivos do

    epitlio do

    intestino delgado

    NOTES:

    It is likely that the

    activity of the Nachannel is under the

    control of

    aldosterone (a

    mineralocorticoid), in

    a manner similar

    with that existent in

    the kidney.

    extrado, enquanto disponvel (at 20076) de: http://medweb.bham.ac.uk/research/toescu/Teaching/GIT2ndYBIOCHEM.html

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    NOTES: 1. The H available for exchange with Na comes from the dissociation ofH2CO3 formed following the diffusion of CO2 from lumen.The formation ofH2CO3 is catalysedby Carbonic anhydrase (not shown); 2. The bicarbonate (HCO3-) imbalance resulting from the exit ofHions is counteractedby the activity of a paired, luminal HCO3/Cl exchange system, which works in conjunction with the Na/H exchange system;

    3 . The resulting Cl load of the enterocyte is dealt withby the activity of the baso-lateral Cl channel. The activity of the latterhelps in building upthe standing osmotic gradient. extrado, enquanto disponvel (at 20076) de: http://medweb.bham.ac.uk/research/toescu/Teaching/GIT2ndYBIOCHEM.html

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    Um elementoimportanteparaahomeostase doCa2+ totalcorporala

    percepodaclulaparatireide,atavsdereceptoressensveisaoCa2+ (CaR).Paralelamente diminuiodos nveisdeCa2+ sangneos, esses receptoresacionamasecreodoParatormnio(PTH).Este

    porsuavez, estimulaaliberaode Ca2+

    sseo e aumentaaproduo renaldoCalcitriol(ou 1,25-VitD)apartirda 25-Vitamin D(25-VitD) notbulocontorcido

    proximaldo nfron.A 1,25-VitDaumentaa expressode canaisde Ca2+ epiteliais(TRPV6) e,juntocom oPTH,oTRPV5

    renal.OTRPV6transportaCa2+

    paraosangue atravsda borda-em-escovadointestinodelgado enquantooTRPV5aumentaa reabsorode Ca2+ noTCdistalno nfron (texto extrado da Fig. 1 do artigooriginal).

    Mecanismos envolvidos na homeostase do Ca2+

    http://arjournals.annualreviews.org/doi/full/10.1146/annurev.physiol.69.031905.161003

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    Nointestinodelgado(sob ao do Calcitriol),ocanal epitelialtransportadorde Ca2+ ,TRPV6que expresso na membranada borda-emescovaintestinal, medeiaoprimeiropassoparaa

    absorotransepitelialde Ca2+ ,Umavezdentrodacl. epitelial,oCa2+ liga-se calbindinaD9Kque tem umpapelcentral notransporte de Ca2+

    intracelularparaa membrana basolateralsemaumentaraconcentraode Ca2+ livreintracelular.Da membrana basolateralparaointerstcio e sangue,oCa2+ liberadopelaCa2+-ATPase PMCA1b epossivelmente envolvendo

    um trocadorNa+/Ca2+ NCX1 (SLC8A1).Areabsoro noTCDistaldo nfron ocorre demaneirasemelhante (sob ao do PTH e doCalcitriol) com asseguintesvariaes:(a)OCa2+ difunde atravsda membranaluminalpelocanalde Ca2+ TRPV5.(b)OCa2+ captadoporambascalbindinaD9Ke calbindinaD28K.(c)OCa2+ saidaclulatantopelotransportador

    PMCA1b Ca2+ -ATPase quantopelotrocadorNCX1 (SLC8A1)Na+/Ca2+ exchanger.Sobcondiesde nveisde Ca2+ elevados nolmendointestinodelgado,oCa2+ absorvidoporviaparacelularatravsdasjunesfirmes(outightjunctions)afavordogradiente transepitelialdoCa2+ .(texto extrado da Fig. 2 do artigo original).

    Mecanismos epiteliais de absoro intestinal e de reabsoro renal de Ca2+

    http://arjournals.annualreviews.org/doi/full/10.1146/annurev.physiol.69.031905.161003

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    Absoro de Vitaminas

    http://www.istoc kphoto.com/stock-illustration-6475935-vitamin-s-table-with-food-icons.php

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    Absoro de Vitaminas HidrossolveisEM CO-TRANSPORTECOM ONSDIO NOJEJUNO

    Schematicofthe absorptive cellsin the smallintestine (enterocytes)andthe transportproteinsinvolvedin netsolute transportfrom the apicalsidetothe basolateralside ofthe epithelium.A:typesofpathwaysinvolvedin the uptake ofsodium bythe cell.Electrogenictransportpathways(1and 2)leadtoa net movementofcharge acrossthe membrane,and electroneutraltransportpathways(3and 4)do notcontribute toacharge

    difference.B:Na+-substrate cotransportersare available forthe absorption ofnutrientsfrom the intestinallumen.Goodman e Percy 2005http://advan.physiology.org/cgi/content/full/29/2/75

    duodeno

    jejuno

    leo

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    http://www.mds.qmw.ac.uk/biomed/kb/metabolism/Micronutrients_files/frame.htm

    Absoro de VitaminasAVitamina B12 (cianocobalamina)absorvida noleodistalpor receptores

    especficosparaocomplexoVit. B12 + Fatorntrinseco,secretadopelasclulas

    parietais.Surge nosangueportaligada transcobalaminaII(umaglobulina) e armazenada nofgado.AfaltadoFIleva anemiaperniciosa.

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    clula parietal

    absoro da

    Vitamina B12

    http://www.uq.edu.au/vdu/HDUAnaemiaMegaloblastic.htm Figuras extradas, enquanto disponveis, de: http://www-ermm.cbcu.cam.ac.uk/03006434h.htm

    Fator Intrnseco e a absoro da Vit. B12

    duodeno

    jejuno

    leoterminal

    (80cm)

    A b d Vit i B

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    A absoro da Vitamina B12Fig. 1(*): Cobalamin metabolism and correspondingcauses of deficiency. Causes of cobalamin deficiency areshown in blue. The metabolic pathway starts when dietary

    cobalamin (Cbl), obtained through animal foods, enters the

    stomach bound to animal proteins (P). Pepsin and

    hydrochloric acid (HCl) in the stomach sever the animalprotein, releasing free cobalamin. Most of the free cobalamin

    is then bound to R-protein (R), which is released from the

    parietal and salivary cells. Intrinsic factor (IF) is also secreted

    in the stomach, but its binding to cobalamin is weak in the

    presence of gastric and salivary R-protein. In the duodenum,

    dietary cobalamin bound to R-protein is joined by cobalamin

    R-protein complexes that have been secreted in the bile.

    Pancreatic enzymes degrade both biliary and dietary

    cobalaminR-protein complexes, releasing free cobalamin.

    The cobalamin then binds with intrinsic factor.

    Thecobalaminintrinsic factor complex remains undisturbed until

    the distal 80 cm of the ileum, where it attaches to mucosal

    cell receptors (cubilin) and the cobalamin is bound to

    transport proteins known as transcobalamin I, II and III (TCI,

    TCII and TCIII). Transcobalamin II, although it represents

    only a small fraction (about 10%) of the transcobalamins, is

    the most important because it is able to deliver cobalamin to

    all cells in the body. The cobalamin is subsequently

    transported systemically via the portal system. Within each

    cell, the transcobalamin IIcobalamin complex

    is taken up bymeans of endocytosis and the cobalamin is liberated and

    then converted enzymatically into its 2 coenzyme forms,

    methylcobalamin and adenosylcobalamin (this process is

    shown in greater detail in Fig. 2).

    * Nitrous oxide, a general anesthetic, causes multiple defectsin cobalamin use, most of which are intracellular and clinically

    relevant only in people who have low or borderline-low serum

    cobalamin levels.

    (*) Veja aqui o artigo original e gratuito: Reviso: Vitamin B12 (cobalamin) deficiency in elderly patients, Adrs et al, 2006

    Veja mais sobre a importncia da Vitamina B12 na seguinte reviso de autoresbrasileiros: Fisiopatologia da deficincia de vitaminaB12 e seu diagnstico

    laboratorial. Paniz et al., 2005 (JBras Patol Med Lab, 41(5), p. 323-34, 2005 (artigooriginal: http://www.scielo.br/pdf/jbpml/v41n5/a07v41n5.pdf)

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    http://www.mds.qmw.ac.uk/biomed/kb/metabolism/Micronutrients_files/frame.htm

    Absoro de vitaminas lipossolveis:micelas e quilomcrons

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    Fig. 33-19 Lipid absorption in the small intestine. Mixed micelles of bile acids and lipid digestion products diffuse through the unstirred layer and amongthe microvilli. As digestion products are absorbed from free solution by the enterocytes, more digestion products partition out of the micelles. The ability of

    micelles to diffuse among the microvilli makes the whole surface of the brush border available for lipid absorption. Transport proteins mediate the

    facilitated transport of fatty acids and cholesterol across the brush border plasma membrane. In the cytosol of the epithelial cell, fatty acids are bound tofatty acid-binding protein and cholesterol is bound to sterol carrier proteins.

    Transporte dasVitaminas

    lipossolveispara a borda-

    em-escovapara absoro

    Vitaminaslipossolveis

    (A, D, E e K)

    camada estacionria de gua (barreira para a difuso de lipdeos)

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    Absorption and transportationVitamin E containedin foodisabsorbed bythe bodyin the intestinesafterthe formation ofmixed micelles by bile acids.Vitamin Eis thentransported bychylomicron tothe liver.Itisgenerallyassumedthatalltocopherolsare absorbed equallyin the intestines,butonly -tocopherolisselectivelytransported by alfa -TTP( alfa -tocopheroltransferprotein)to blood because ofthe highaffinityofthe transfer

    protein in the liverfor alfa-tocopherolhttp://www.skillchemical.com/news.asp?id=73

    Exemplo de transporte: Vitamina E

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    VitaminasLeia mais:

    Biodisponibilidade de vitaminas lipossolveisMouro et al., 2005(*)

    Nossa vida depende destas pequenas molculas: as

    vitaminas so essenciais para as funes biolgicas.QMCWEB-UFSC(**)

    Sobre Vitamina D: http://vitamind.ucr.edu

    (*)Rev. Nutr. vol.18 no.4 Campinas July/Aug. 2005. Caso necessite,solicite-me uma cpia.

    (**)Revista eletrnica do Departamento de Qumica - UFSC