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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