Vitaminele · Vitaminele •molecule organice •majoritatea –suplimente alimentare provitamine...
Transcript of Vitaminele · Vitaminele •molecule organice •majoritatea –suplimente alimentare provitamine...
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Vitaminele
• molecule organice
• majoritatea – suplimente alimentare
provitamine
• intestinul uman(colon)
1012 microorganisme(bacterii, drojdii, paraziti)
Biosinteza vitaminelor
B12, B7, K
https://shop.drberg.com/
http://www.freegrab.net/
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Funcții
Diviziunea celulara
Coagulareasangelui
Enzime
DeficienteStructura
membranelor
Analogii(medicamente)
Hormoni
beriberi, pelagra,
Anemia megaloblastica si
scorbut
Cofactori
B9
B12
Calcitriol
A
D
K
E
B12 B6
CoAB5 (precursor)
ac. folic
AnticancerigeniAntibiotice
An. Vit. K
AnticoagulantVit. liposolubile
Integritate membrane Scorbut (vit. C)
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Terminologie
Vitamine Vita + “amine”
1912 Casimir Funk – biochimist
polonez/american
bolile sunt cauzate de deficiente alimentare
Descopera vitamina B1
Beri-beri
(boala a SN periferic)
Orient
(orez decorticat)
https://alfa-img.com/
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Casimir Funk
vitamina B1
vitamina B2
vitamina Cvitamina D
https://shop.medindia.com
http://www.biotechvisioncare.com/
https://www.walmart.ca/
https://ro.pinterest.com/
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Clasificarea vitaminelor
In functie de
solubilitate
Inainte de identificarea
structurii chimiceB1, B2, ……
Diferiti compusi chimici Aceeasi activitate biologica
Vitameri
Liposolubile (A, D, E, K)
Solubile (B, C)
https://www.natur-clinic.ro/
https://www.alibaba.com/
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Vitamina A - istoric
Vitamine liposolubile
Nikolai Lunin
1880
Substanta necunoscuta in lapte necesara
pentru nutritie
Experimente pe soareci hraniti cu
componente izolate din lapte sau lapte
neprocesat
Carl A. Socin
Experimente pe soareci hraniti
100 zile
+ galbenus de ou
30 zile
-
https://respectfulinsolence.com/
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Vitamina A - istoric
Vitamine liposolubile
Frederick G. Hopkins
http://www.bbc.co.uk/
1906-“ factori dietetici sunt necesari
pentru sustinerea vietii”
Wilhelm Stepp
Substanta esentiala din lapte
greu solubila
1918 - Substanta factor de
crestere – “fat-soluble A”
1920 – vitamina A
https://www.cartoonstock.com/
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Vitamina A - istoric
Vitamine liposolubile
Paul Karrer
http://www.paul-ehrlich.de/
Elucidarea structurii chimice a vitaminei A (1932)
Premiul Nobel in Chimie (1937)
Elucidarea structurilor chimice
Vitamina B2
(1938)
Tocoferol
(1935)
Harry Holmes si Ruth Corbet
izolarea si cristalizarea vitaminei A -1937
Sinteza vitaminei
David Adriaan van Dorp si Jozef Ferdinand Arens (1946)
Otto Isler si colab. (1947)
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Retinoidele
Compusi cu 20 atomi de carbon
Au în componență un ciclu -iononic
Iononele – cetonele din uleiul de trandafiri
α-ionona
-ionona
damascenona
https://ro.pinterest.com
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Structura vitaminei A
Vitamina A - retinoide
retinolul - depozit
retinal – procesul vederii
Ac. retinoic - crestere embrionara
Vitamine liposolubile
20 atomi de carbon
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Variante ale vitaminei A
Retinol-glucuronida
plasma/bila(metaboliti mai polari)
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Conversia provitaminei A
Vitamina A 1U 0,0006 mg -caroten
Retinal Ac. retinoic
+ HSA
-caroten + lipoproteine
~ 10 %
Retinolul (celulele
mucoasei
intestinale)
Oxigenazei
(citoplasma
eritrocite)
Retinol 1-esterificare
Circulatia
limfatica
2-legare de
proteina
(chilomicroni)
Echivalent retinol (1 RE)
1g trans-retinol sau 6 g -caroten
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Luteina
http://www.super-lutein.net
Tipuri de carotenoizi
Importanta: Filtre pentru lumina albastra, antioxidanti
Zeaxantina
600 carotenoide
plante
bacterii
Luteina
Zeaxantina
galbenus de ou
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licopen
Crocetina – supliment impotriva oboselii
Tipuri de carotenoizi
Licopenul
boli oculare
tratament infertilitate barbati
osteoporoza
https://s3.amazonaws.com/ttac-com/
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Activitatea antioxidantă a β-carorenului
Yusuf, Y. M. et al., International Journal of
Nanomedicine, 7, 4311-21, 2012
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Orientarea diferita a carotenilor în membrane
https://www.dougcookrd.com/
Johnson, Q.J. et al., 2018, PhysChemChemPhys, 5, 3795
Carotenoidele
Induc subțierea stratului bilipidic
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http://products.mercola.com/
Activitatea antioxidantă a β-carorenului
F = 2,2’-azobis(2-amidino-propane) dihydrochloride (AAPH)
Trolox
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Conversia esterilor retinilici
Ball, G.F.M.-Vitamins:their role in the human body, p165
Blackwell Science (2004)
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Absorbtia si transportul vitaminei A
Peruseck and Maeda, Nutrients 2013, 5(7), 2646-2666
Proprietatile celulelor hepatice stelate (HSC) sunt mediate
de alte celule ale sistemului imunitar
Weiskirchen and Tacke, Liver Immunol., 2014, 3(6),
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Functii/Rol
Vitamina A
Retinolul
Retinal
Mentinere membranemielinice
Dezvoltareplancenta
Hormon
Sinteza glicoproteine
Copieregene
Procesul vederii
Tratarea
Psoriasis Acnee
Acidul
retinoic
-carotenul
antioxidant
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Procesul vederii
Retinolul (fluxul sanguin) → retină (celule epiteliale; esterificat)
7 milioane130 milioane
→ hidroliza - retinol → cis-retinal
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Porfiroxina, iodopsina si cianopsinaProteine transmembranare + 11-cis-retinal
sensibili la rosu, verde si albastru
Conurile - 3 pigmenti
Procesul vederii
http://www.cudo.jp/
-L
-M
-S
2,3 tipuri de conuri
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Celulele cu conuri
Procesul vederii
Sensibilitate scazuta
Densitate mare-centrul retinei
Imagini fine
colorate
Celulele cu bastonase
Sensibilitate scazuta
Periferia retinei
Nu permit diferentierea
culorilor/detaliilor
opsina (glicoproteina) + cis retinal
https://micro.magnet.fsu.edu/
Bhagavan & Ha, Essential of
Biochemical Biochemistry
with Clinical Cases, Elsevier, 2011
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Procesul vederii
Bhagavan & Ha, Essential of Biochemical Biochemistry
with Clinical Cases, Elsevier, 2011
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Ciclul vederii
Bavik, C. et al., PLoS ONE 10(5), 2015
Biochemistry and Medical Genetics lecture notes,
Kaplan Medical, 2017
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Retinolul
dezvoltarea limfocitelor
Raspuns imun
Rezistenta la infectii
Acidul retinoic
activarea
limfocitelor T
Rolul
R. Weiskirchen, F. Tacke, Hepatobiliary Surg Nutr
2014;3(6):344-363
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https://michellepetersen76.files.wordpress.com/
Mutatie a proteinei RPB4 care transportă retinolul
Defecte genetice – transport deficitar al retinolului
Plasma
Serul
Saliva
Urină
Lapte
Lichidul cefalorahidian
Culturii celulare
Detecta cu anticorpi a RBP4
https://www.abcam.com/
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Retinolul-fosforilat transport de manoza
Sinteza glicoproteinelor
De Luca, L. Et al., Pure&Appl Chem, 1979;51:581
Roth, J. et al., Histochem
Cell Biol, 2008, 129(2), 163
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Retinalul Actiune antioxidanta Fractiuni nucleare(ficat, splina)
Fractiuni
mitocondriale(ficat)
Efect prooxidant Fractiuni mitocondriale(rinichi, splina)
Fractiuni microzomiala(splina)
Rolul
http://www.skinmed.com/
Retinalul Retinalul Palmitat de retinil
iritabilitate
Activare
Capacitate de absorbție
mai iritant mai putin iritant
mai usoara mai dificla
mai usoara mai dificila
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Deficientele vitaminei A
Orbirea nocturna-blocarea resintezei rodopsinei.
Afecteaza cresterea oaselor si formarea dintilor
Degenerarea straturilor mielinice.
Cheratinizarea mucoaselor
Necesarul de
vitamina A
700 g femei
900 g barbati
Boli reproductive
Necesarul si deficienta de vitamina A
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Deficientele vitaminei A
“In … four [southeast Asian] countries alone at least 500,000
preschool age children every year develop active xerophthalmia
involving the cornea. About half of this number will be blind and
a very high proportion, probably in excess of 60%, will die. The
annual prevalence for these same countries of non-corneal
xerophthalmia is many times higher, probably on the order of 5 million …
There can be no doubt about the claim that vitamin A deficiency
is the most common cause of blindness in children and one of the
most prevalent and serious of all nutritional deficiency diseases”
D. S. McLaren
xerophthalmia
Incidenta cazurilor de orbire
in lume la copii
Cauzele orbirii la copiihttp://www.cehjournal.org/
https://draxe.com
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Deficientele vitaminei A
Retinolul din laptele matern5-7 g/L colostru
3-5 g/L laptele traditional
1,4-2,6 g/L laptele matur
<1,1 g/L laptele matur – deficiente - vit A
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Surse vit A
Animale
Vegetale
Ficat peste(cod, rechin)
Ficat
(ovin, bovin)
Unt
Oua
Lapte
Frunze
Spanac
Varza
Fructe PapaiaMango
http://www.aboutfishonline.com/
http://www.chrom-china.com/
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Hipervitaminoza A - simptome
Antagonistii vitaminii A
durerile de cap
slabiciune
hipertensiune
CitralulInhiba sinteza
acidului retinoic
Benzoatul
Brombenzen
deformatii congenitale (fat)
osteoporoza
http://orthoinfo.aaos.org/
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Vitamina D
Colecalciferol (vitamina D3) - sintetizat in piele
Absorbtia - intestinul subtire
(sarurilor biliare)
Transport-+ prot din plasma
Depozitarea - ficat, tesutul adipos.
http://www.wardelab.com/
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Vitamina D
Ergocalciferolul (vitamina D2) – iradiere fungi
Ergot corn secara
Drojdie
http://www.studyandexam.com/
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Vitamina D
Ergocalciferolul (vitamina D2) – sinteza in drojdii
R.B. Jäpelt and J. Jakobsen,
Frontiers in Plant Science/ PlantPhysiology,2013,4,136,2
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Vitamina D
Absorbția, transportul și depozitarea
Sascha Kopic, John P. Geibel
Physiological Reviews, 2013, 93(1), 189-268
Iruzubieta et al., World J Hepatol,
2014; 6(12): 901-915
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Functiile calcitriolului
Netteras, Essential Biochemistry, Elsevier, 2017
Pacheco, H.A. et al., 2018,
Frontiers in Genetics, 9, 465
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In ficat
In rinichiCuantificareDeficienta D3 ?
Stimuleaza sinteza proteica(interactiune cu factori
de transcriptie-receptori nucleari)
Mentine nivelul de Ca2+ si fosfor din sange
Derivati activi ai vitaminei D
Producerea catelicidinei (antibiotic natural)
http://dmakesadifference.com/
http://scielo.isciii.es/
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Forme ale vitaminei D
myaimstore.com
http://freetheanimal.com/
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Functiile calcitriolului
• creste abs. Ca2+ și PO43- in intestin;
• formarea si mineralizarea oaselor;
• reducere excretia calciului si
fosforului din rinichi;
• este un hormon
stimuleaza celulele T, macrofagele
• poseda proprietati anticancerigene
(prin incetinirea diviziunii celulare).
journal.frontiersin.org
http://www.mdpi.com/nutrients/
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Deficientele vitaminei D
Rahitism OsteoporazaCaderea
dintilor
Hipervitaminoza D
- pierderea poftei de mâncare
- ruperea oaselor
- calcifierea rinichilor
- psoriasisulhttp://www.shantihomoeos.com/
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Surse vit D
Peste
Vegetale
Somon
Sardine
Macrou
Ficat ton
Unt
Galbenus
Ciuperci
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Vitamina E
8 compusi
În plasmă - tocoferolii
+ lipaza
În ficat – ½ tocoferol
4 tocoferoli
4 tocotrienoli
Derivati de
6-hidroxi-croman
https://www.nap.edu/openbook/
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Absorbtia, transportul si stocarea vitaminei E
Absorbiţia-intestinul subţire - acizilor biliari
Transportullipoproteina
lipaza
lipoproteine
circulatorii
http://www.basfanimalnutrition.de/
Depozitareatesut adipos
ficat
muschi
http://image.slidesharecdn.com/
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Absorbtia, transportul si stocarea vitaminei E
Schmölz et al., World J Biol Chem. Feb 26, 2016, 7(1): 14-43
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Functiile vitaminei E
Antioxidant – in membrane / lipide nesaturate
-tocoferolul –mentinerea tonusului
muscular
sinteza hemului (hemoproteine)Activeaza sintetaza
acidului aminolevulinic (ALA)
previne distrugerea oxidativa
a vitaminei si provitaminei A
http://www.mdpi.com/pharmaceutics/
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Functiile vitaminei E
Antioxidant – in membrane / lipide nesaturate
http://www.escrutgers.com/
http://www.alpfmedical.info/http://old.aor.ca/wp-content/
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Determinarea activitatii antioxidante
Antioxidant – in membrane / lipide nesaturate
DPPH incolor
TROLOX (antioxidant)
acid 6-hidroxi-2,5,7,8
tetrametilcroman-2-carboxilic
Analog al vitaminei E
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Functiile vitaminei E
Antioxidant – in membrane / lipide nesaturate
http://lpi.oregonstate.edu/
Previne distrugerea provitaminei A
http://eng.ege.edu.tr
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Functiile vitaminei E
Antioxidant – in membrane / lipide nesaturate
Netteras, Essential Biochemistry, Elsevier, 2017
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Functiile vitaminei E
Stimulează spermatogeneza
https://www.slideshare.net/
Inhiba citokinele cytokinele IL-1β
proinflamatoare
Jang et al., Free Radical Biology and Medicine, 95,
2016, 190-199
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Determinarea activitatii antioxidante
http://media.mercola.com/
Oxygen radical absorbance capacity (ORAC)
http://www.cellbiolabs.com/sites/
http://i1239.photobucket.com/
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Deficienţa vitaminei E
anemia hemolitică
sterilitate
distrofie musculară
boli neurodegenerative
uscaciunea pielii
http://www.natural-homeremedies.com/
https://s-media-cache-
ak0.pinimg.com/
Bestram and Tanzi, JCI, 2005
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Surse de vitamina E
http://steadyrun.com/wp-content/
https://s-media-cache-ak0.pinimg.com/
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Utilizări terapeutice
-tocoferil-succinat (antineoplazic)
prevenirea cancerului de prostată??(+Se)
menţinerea vâscozităţii sângelui - α
Vitamina E utilizari
http://pubs.rsc.org/services/ http://www.livescience.com/images/
https://images.sciencedaily.com/
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Ulei de palmierLotiuni
Tocotrienoli utilizari
http://i2.wp.com/jeffreydachmd.com/
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Tocotrienoli structura
http://www.drpasswater.com