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Cooking Creates New Toxic Substances In Food
Adapted from ”New Substances In Prepared Food”€?? by Wai Genriiu
See Footnotes for 135 scientific references!
Cooking food is always like doing a chemical experiment in high school. Due to heat, cooking or preparing food creates new substances. Most of these new substances come from proteins reacting with carbohydrates. Some of these substances cause cancer or brain diseases and impair neurotransmitter function and metabolism.
Many of these new substances are heterocyclic amines (HCA). Many of these HCA are directly or indirectly physically addictive.(1) Due to the heat of cooking, these HCA originate from the interaction between protein and carbohydrates and / or creatine (in red meat) or nitrate (in vegetables). Some examples :
tryptophan + form- / acet-aldehyde = 1-methyl-1,2,3,4-tetrahydro-beta-carboline (pro-mutagenic) (2)
tryptophan + glycolaldehyde = 1-hydroxymethyl-tetrahydro-beta-carboline (3)
tryptophan + sugars (by freezing) = 1,1'-ethyliden-ditryptofaan (very toxic) (4)
serotonine + formaldehyde = 6-hydroxy-tetrahydro-beta-carboline (5)
serotonine + acetaldehyde = 6-hydroxy-1-methyl-tetrahydro-beta-carboline (6)
tyramine + nitrite = 3-diazotyramine(4-(2-aminoethyl))-6-diazo-2,4-cyclohexadienone (carcin.)(7)
salt + nitrite + protein / sugar = 2-chloro-4-methylthiobutanoate (mutagenic) (8)
glutamate + sugars = 2-amino-6-methyldipyrido-(1,2-a:3',2'-d)imidazole (carcinogenic) (9)
glutamate + sugars = 2-aminodipyrido-(1,2-a:3',2'-d)imidazole (carcinogenic)(9)
When aldehydes react upon cyclic amino acids or -amines (like tryptophan, tryptamine, serotonine, phenylalanine, tyrosine, dopamine, tyramine, aniline), mostly beta-carbolines and isoquinolines originate. When creatinine (from meat) is involved, mostly imidazoquinolines and imidaziquinoxalines originate. (10) (Glutamate and tryptophan are amino acids, tyramine and serotonine are amines, and aldehydes are sugars)
In What Foods?
Almost all cooked or prepared foods contain:
9H-pyrido(3,4-b)indole = beta-carboline = tryptophan / tryptamine + aldehydes (11)
1-methyl-9H-pyrido(3,4-b)indole = 1-methyl-beta-carboline = tryptophan / tryptamine + aldehydes (11)
These substances influence benzodiazepine receptors in the brain, and indirectly lots of other neurotransmitters. (12) If these substances further react upon amines like aniline, they even become mutagenic (23). How much HCA originate depends on how much protein the food contains and on how much the food is heated. (14) Because red meat contains both lots of protein and creatinine (creating creatine), prepared red meat contains the most HCA, especially when grilled (15). Besides prepared red meat, also prepared fish, soy and poultry contain lots of HCA. (16) Flavor-enhancers and bouillon contain protein-concentrates and therefore contain lots of HCA too. (11) But also prepared foods containing less protein contain HCA, like prepared grains (17) and -vegetables (18), and even foods like beer, soy sauce and canned orange juice. (19) For example:
Meat contains too much creatine (20):
2-amino-1-methyl-6-(4-hydroxyfenyl)-imidazo-(4,5-b)pyridine (mutag.) = creatine + tyrosine + glucose (21)
Soy contains globulins:
2-amino-9H-pyrido(2,3-b)indole (mutagenic) (22) = soy-globulins + sugars (23)
2-amino-3-methyl-9H-pyrido(2,3-b)indole (mutagenic) (24) = soy-globulins + sugars (23)
Prepared fish contains (25):
3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (mutagenic)(26) = tryptophan + acetaldehyde (27)
3-amino-1-methyl-5H-pyrido(4,3-b)indole (mutagenic)(26) = tryptophane + acetaldehyde (28)
Cooked Vegetables contain nitrite:
cancerous N-nitroso-compounds = amines + nitrite + sugars
specific N-nitroso-compound ;
4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone (cancerous) = tyramine + nitrite + sugars (7)
Cooked Cabbages contain thiocyanates ;
toxic (29) tetrahydro-beta-carboline-derivates = isothiocyanate + tyramine / serotonine etc.
Cooked vegetables contain also flavonoids:
mutagenic glycosides (30) = flavonods + heat
Canned orange juice contains free amino acids, which easily combine with aldehydes to create heterocyclic amines.
What Can HCA Do?
1. Act like Neurotransmitters
Some HCA, like beta-carbolines, can directly influence neurotransmitter-receptors, like benzodiazepine receptors. Simply because the body also composes beta-carbolines to function as neurotransmitters. HCA can also occupy receptors of other neurotransmitters, like serotonine- and dopamine receptors. Especially when they are composed of the same amines. Some examples ;
3-methoxycarbonyl-beta-carboline acts through different receptors (31) and increases secretion and decomposition of dopamine, like physical stress does. (32) It enhances 'irrational' aggressive behaviour (33), and decreases social interaction (34).
3-ethoxycarbonyl-beta-carboline, is hypnotic and anaesthetic (35), and inhibits investigative behaviour (36) and social interaction. (37) In dominant types it enhances aggressive behaviour, but inhibits sexual appetite. (38) It increases epinephrine- (39) and cortisol-level, blood pressure and heart rate (40), and increases secretion and decomposition of dopamine (41), like physical stress does.
3-Hydroxymethyl-beta-carboline ; though hypnotic (42), it negatively affects sleep (43).
3-N-methylcarboxamide-beta-carboline enhances reckless- (44) and aggressive behaviour (45), and inhibits sexual appetite. (46) It generally inhibits (47), but locally stimulates norepinephrine secretion. (48) It increases glutamate- (49), ACTH- and Substance P-secretion (50), increases blood pressure (51) and though anaesthetic (52), causes physical stress. (53).
3-Methylcarbonyl-6,7-dimethoxy-4-ethyl-beta-carboline blocks GABA receptors (54), increases GABA- and glycine-level, decreases glutamate- and aspartate-level (55), increases corticosterone-, epinephrine- and norepinephrine-secretion(56), decreases serotonine-secretion (57) and increases norepinephrine-receptor-activity. (58) It enhances the effect of cocaine (59), causes anxiety (60) and suppresses immune system activity. (61)
3-Ethylcarbonyl-6-benzyloxy-4-methoxymethyl-beta-carboline is sedative (62), causes amnesia (63), and blocks beta-oestradiol-LH (lutinizing hormone) interaction. (64)
3-Ethylcarbonyl-5-benzyloxy-4-methoxymethyl-beta-carboline strongly stimulates appetite. (65)
3-Ethylcarbonyl-5-isopropyl-4-methyl-beta-carboline causes restlessness (66), sleeplessness (67), and decreases social interaction. (68)
Besides 'normal' beta-carbolines, prepared foods also contain tetrahydro-beta-carbolines. (69).
Tetrahydro-beta-carboline stimulates craving for alcohol (70), increases heart rate and blood pressure (71), and like 5-methoxy-tetrahydro-beta-carboline and 5-hydroxy-tetrahydro-beta-carboline increases prolactine-level and affects serotonine receptors. (72)
6-methoxy-tetrahydro-beta-carboline increases norepinephrine- and ACTH- secretion, and decreases serotonine- and growth hormone secretion. (73)
2-Fenylpyrazolo(4,3-c)quinoline-3(5H)-one is sedative (74), increases corticosterone-level (75) and decreases specific benzodiazepine-receptors in the brain. (76)
2. Cause Cancer
Part of the process causing cancer is mutagenic substances damaging cell-DNA. (see site5) Some HCA in prepared food are mutagenic.DNA-damage increases linearly with intake of HCA. (77) How cancerous HCA are is partly dependent on how much nitrogen they contain. (78) Salt, protein and nitrite (from vegetables) can supply nitrogen to react upon HCA. And nitrosated HCA are even more cancerous. (79) Some of the most widespread mutagenic HCA in prepared foods are:
pyridoindole (80) (amino-gamma-carboline)
2-amino-9H-pyrido(2,3-b)indole(81) (amino-alpha-carboline)
2-amino-3-methyl-9H-pyrido(2,3-b) (82)
3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole(83)
3-amino-1-methyl-5H-pyrido(4,3-b)indole(84)
1-methyl-3-carbonyl-1,2,3,4-tetrahydro-beta-carboline(85).
4-aminobiphenyl(86)
4,4'-methylenedianiline (87)
3,2'-dimethyl-4-aminobiphenyl(88)
1,2-dimethylhydrazine(89)
phenyl-hydroxylamine (90)
O-acetyl-N-(5-phenyl-2-pyridyl)-hydroxylamine(91)
2-amino-3-methylimidazo(4,5-f)quinoline(92)
2-amino-3-methylimidazo(4,5-f)quinoxaline(93)
2-amino-3,4-dimethylimidazo(4,5-f)quinoline (94)
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (95)
2-amino-3,4,8-trimethylimidazo(4,5-b)pyridine(96)
2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline (97)
2-amino-3,7,8-trimethylimidazo(4,5-f)-quinoxaline(98)
2-amino-n,n,n-trimethylimidazo-pyridine(99)
2-amino-n,n-dimethylimidazopyridine (100)
2-amino-4-hydroxymethyl-3,8-dimethylimidazo-(4,5-g)-quinoxaline(101)
2-amino-1,7,9-trimethylimidazo-(4,5-g)-quinoxaline (101)
2-amino-1-methyl-6-phenylimidazo-(4,5-b)-pyridine(102)
3. Cause Brain Diseases
Some HCA are directly toxic to the brain, like common quinolines, which enter the brain through the dopamine-transport system. (103) Other common HCA (like pyridines (104) and beta-carbolines (105)) only become toxic to the brain after they have been partly decomposed by different enzymes (106) in the body. Originally , these enzymes have to, and do protect the brain against toxic substances, but part of the HCA are accidentally transformed into more toxic substances. (107) Obviously nature didn't count on 'strange' HCA from prepared food. Pyridines can only occupy dopamine-receptors (108), and therefore are toxic to thesereceptors only. Partly decomposed pyridines are more toxic than the originals (109), but the originals do decrease dopamine- (110), norepinephrine- (111) and mostly serotonine-level (112). The destruction of receptors in the brain causes brain-diseases like Alzheimer’s, Parkinson’s and schizophrenia. Some toxic-to-the brain HCA are:
3-N-butylcarbonyl-beta-carboline (113)
3-N-methylcarboxamide-beta-carboline(113)
2-methyl-1,2,3,4-tetrahydro-beta-carboline(114)
2-methyl-1,2,3,4-tetrahydro-isoquinoline(114)
quinolinate (115)
quisqualinate (116)
tetrahydroisoquinoline(117)
1-benzyl-tetrahydro-isoquinoline(117)
N-methyl-(R)-salsolinol(118)
N-methyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline(119)
6-methoxy-1,2,3,4-tetrahydro-isoquinoline(119)
2,4,5-trihydroxyphenylalanine(120)
6-hydroxy-dopamine(121)
N-methyl-4-fenyl-1,2,3,6-tetrahydropyridine(122)
1-methyl-4-fenyl-1,2,3,6-tetrahydropyridine(123)
1-methyl-4-fenyl-1,2,5,6-tetrahydropyridine(124).
4-fenyl-1,2,3,6-tetrahydropyridine(125)
4-fenylpyridine(125)
3-acetylpyridine(126)
1-methyl-4-phenyl-1,4-dihydropyridine(127)
1-methyl-4-cyclohexic-1,2,3,6-tetrahydropyridine(128)
1-methyl-4-(2'-methylfenyl)-1,2,3,6--tetrahydropyridine (129)
1-methyl-4-(2'-ethylfenyl)-1,2,3,6-tetrahydropyridine (130)
1-methyl-4-(3'-methoxyfenyl)-1,2,3,6-tetrahydropyridine(131)
1-methyl-4-(methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine(132)
Though toxic pyridines create oxidative radicals (133) and decrease antioxidant-level (134), the intake of antioxidants cannot prevent brain damage by toxic pyridines. (135)
Additives
Food preparation is primarily there to make edible what is not so edible. Additives are primarily there to make fake food last longer, and to make you eat more. Taste enhancers for example are mostly concentrated protein, filled with lots of physical addictive beta-carbolines that make you eat more. Glutamate (popular in the Chinese kitchen) indirectly influences the same (Benzodiazepine) receptors.
Footnotes
Abstracts of most sources can be found at the National Library of Medicine
(1) Loscher, W. et al, Withdrawal precipation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta-carboline abecarnil. Naunyn Schmiedebergs Arch. Pharmacol. 1992 / 345 (4) / 452-460. , De Boer, S.F. et al, Common mechanisms underlying the proconflict effects of corticotropin, a benzodiazepine inverse agonist and electric foot shock. J. Pharmacol. Exp. Ther. 1992 / 262 (1) / 335-342. , Little, H.J. et al, The benzodiazepines : anxiolytic and withdrawal effects. Neuropeptides 1991 / 19 / suppl. 11-14. , Eisenberg, R.M. et al, Effects of beta-carboline-ethyl ester on plasma corticosterone -- a parallel with antagonist-precipated diazepam withdrawal. Life Sci. 1989 / 44 (20) / 1457-1466. , Maiewski, S.F. et al, Evidence that a benzodiazepine receptor mechanism regulates the secretion of pituitary beta-endorphin in rats. Endocrinology 1985 / 117 (2) / 474-480.
(2) (no author listed) Tetrahydro-beta-carbolines in foodstuffs, urine, and milk : physiological implications. Nutr. Rev. 1991 / 49 (12) / 367-368.
(3) Papavergou, E. et al, Tetrahydro-beta-carboline-carboxylic acids in smoked foods. Food Addit. Contam. 1992 / 9 (1) / 83-95.
(4) Simat, T. et al, Unerwünschte Nebenprodukte in biotechnologisch hergestelltern L-tryptophan. GIT Fachzeitschrift für das Laboratorium 1996 / H.4 /339-344.
(5) Rommelspacher, H. et al, Is there a correlation between the concentration of beta-carbolines and their pharmacolodynamic effects ? Prog. Clin. Biol. Res. 1982 / 90 / 41-55.
(6) Airaksinen, M.M. et al, Affinity of beta-carboline on rat brain benzodiazepine and opiate binding sites. Med. Biol. 1980 / 58 (6) / 341-344.
(7) Wakabayashi, K. et al, Recently identified nitrite-reactive compounds in food : occurence and biological properties of the nitrosated products. IARC Sci. Publ. 1987 / 84 / 287-291.
(8) Jolivette, L.J. et al, Thietanium ion formation from the food mutagen 2-chloro-4-(methylthio)butanoic acid. Chem. Res. Toxicol. 1998 / 11 (7) / 794-799.
(9) Sugimura, T. et al, Carcinogenic, Mutagenic, and Comutagenic Aromatic Amines in Human Foods. Natl. Cancer Inst. Monogr. 1981 / 58 / 27-33.
(10) Overvik, E. et al, Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. Carcinogenesis 1989 / 10 (12) / 1293-1301. , Yoshida, D. et al, Formation of mutagens by heating foods and model systems. Environ. Health. Perspect. 1986 / 67 / 55-58.
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(22) Okogoni, H. et al, Induction of aberrent cryptfoci in C57BL/6N mice by 2-amino-9H-pyrido(2,3-b)indole (AalphaC) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) Cancer Lett. 1997 / 111 (1-2) / 105-109. , Zhang, X.B. et al, Intestinal mutagenicity of two carcinogenic food mutagens in transgenic mice : 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine and amino(alpha)carboline. Carcinogenesis 1996 / 17 (10) / 2259-2265. , Yoo, M.A. et al, Mutagenic potency of heterocyclic amines in the Drosophila wing spot test and its correlation to carcinogenic potency. Jpn. J. Cancer Res. 1985 / 76 (6) / 468-473.
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(24) Pfau, W. et al, Characterization of the major DNA adduct formed by the food mutagen 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC) in primary rat hepatocytes. Carcinogenesis 1996 / 17 (12) / 2727-2732. , Pfau, W. et al, Pancreatic DNA adducts formed in vitro and in vivo by the food mutagens 2-amino-1-methyl-6-phenylimidazo(4,5-b)prydine (PhIP) and 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC). Mutat. Res. 1997 / 378 (1-2) / 13-22.
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(104) Mandir, A.S. et al, Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 1999 / 96 (10) / 5774-5779. , Harik, S.I. et al, On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity : the effect of perinigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, its metabolite and their analogues in the rat. J. Pharmacol. Exp. ther. 1987 / 241 (2) / 669-676. , Frei, B. et al, N-methyl-4-phenylpyridinium (MPP+) together with 6-hydroxydopamine or dopamine stimulates Ca2+ release from mitochondria. FEBS Lett. 1986 / 198 (1) / 99-102. , Heikkila, R.E. et al, Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase-B. Eur. J. Pharmacol. 1985 / 116 (3) / 313-317. , Heikkila, R.E. et al, Dopaminergic neurotoxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats : implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Neurosci. Lett. 1985 / 62 (3) / 389-394. , Mytilineou, C. et al, 1-methyl-4phenylpyridine (MPP+) is toxic to mesencephalic dopamine neurons in culture. Neurosci. Lett. 1985 / 57 (1) / 19-24.
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(106) Fonne-Pfister, R. et al, MPTP, the neurotoxin inducing Parkinson's disease, is a potent competitive inhibitor of human and rat cytochrome P450 isozymes (P450buf1, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem. Biophys. Res. Commun. 1987 / 148 (3) / 1144-1150. , Naoi, M. et al, Metabolism of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in a rat pheochromocytoma cell line, PC12h. Life Sci. 1987 / 41 (24) / 2655-2661. , Heikkila, R.E. et al, Studies on the oxidation of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase B. J. Neurochem. 1985 / 45 (4) / 1049-1054. , Fuller, R.W. et al, Mechanisms of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity to striatal dopamine neurons in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 1985 / 9 (5-6) / 687-690. , Heikkila, R.E. et al, Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by MAO inhibitors. Nature 1984 / 311 (5985) / 467-469.
(107) Pai, K.S. et al, Protection and potentiation of MPTP-induced toxicity by cytochrome P450 inhibitors and inducer : in vitro studies with brain slices. Brain. Res. 1991 / 555 (2) / 239-244. , Shahi, G.S. et al, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity : partial protection against striato-nigral dopamine sepletion in C57BL/6J mice by cigarette smoke exposure and by beta-naphthoflavone-pretreatment. Neurosci. Lett. 1991 / 127 (2) / 247-250.
(108) Melamed, E. et al, Dopamine, but not norepinephrine or serotonine uptake inhibitors protect mice against neurotoxicity of MPTP. Eur. J. Pharmacol. 1985 / 116 (1-2) / 179-181.
(109) Heikkila, R.E. et al, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse : relationships between monoamine oxidase, MPTP metabolism and neurotoxicity. Life Sci. 1985 / 36 (3) / 231-236. , Melamed, E. et al, Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice. Eur. J. Pharmacol. 1985 / 114 (1) / 97-100.
(110) Wilson, J.A. et al, MPTP causes a non-reversible depression of synaptic transmission in mouse neostriatal brain slice. Brain Res. 1986 / 368 (2) / 357-360.
(111) Wu, W.R. et al, Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci. 1999 / 65 (2) / 157-164. , Pileblad, E. et al, Catecholamine-uptake inhibitors prevents the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in mouse brain. Neuropharmacology 1985 / 24 (7) / 689-692. , Gerhardt, G. et al, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse : an in vivo electrochemical study. J. Pharmacol. Exp. Ther. 1985 / 235 (1) / 259-265.
(112) Lee, E.H. et al, Comparitive studies of the neurotoxicity of MPTP in rats. Chin. J. Physiol. 1992 / 35 (4) / 317-336. , Hara, K. et al, Reversible serotinergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse striatum studied byneurochemical and immunohistochemical approaches. Brain Res. 1987 / 410 (2) / 371-374.
(113) Malgrange, B. et al, beta-Carbolines induce apoptotic death of cerebellar granule neurones in culture. Neuroreport 1996 / 7 (18) / 3041-3045.
(114) Perry, T.L. et al, 4-Phenylpyridine and three other analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lack dopaminergic nigrostriatal neurotoxicity in mice and marmosets. Neurosci. Lett. 1987 / 75 (1) / 65-70.
(115) Harris, C.A. et al, Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid. Br. J. Pharmacol. 1998 / 124 (2) / 391-399. , Levivier, M. et al, Quinolinic acid-induced lesions of the rat striatum : quantitative autoradiographic binding assessment. Neurol. Res. 1998 / 20 (1) / 46-56.
(116) Pai, K.S. et al, Quisqualic-acid-induced neurotoxicity is protected by NMDA and non-NMDA antagonists. Neurosci. Lett. 1992 / 143 (1-2) / 177-180. , Zinkand, W.C. et al, Quisqualate neurotoxicity in rat cortical cultures : pharmacology and mechanisms. Eur. J. Pharmacol. 1992 / 648 / 355-357.
(117) Nagatsu, Isoquinoline neurotoxics in the brain and Parkinson's disease. Neurosci. Res. 1997 / 29 (2) / 99-111.
(118) Naoi, M. et al, Dopamine-derived endogenous 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat : biochemical ,pathological and behavioral studies. Brain. Res. 1996 / 709 (2) / 285-295. , Naoi, M. et al, Enzymatic oxidation of the dopaminergic neurotoxin 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, into 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion. Life Sci. 1995 / 57 (11) / 1061-1066. , Maruyama, W. et al, N-methyl(R)salsolinol produces hydroxyl radicals : involvement to neurotoxicity. Free Radic. Biol. Med. 1995 / 19 (1) / 67-75.
(119) McNaught, K.S. et al, Inhibition of complex 1 by isoquinoline derivates structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Biochem. Pharmacol. 1995 / 50 (11) / 1903-1911.
(120) Skaper, S.D. et al, Characterization of 2,3,4-trihydroxyphenylalanine neurotoxicity in vitro and protective effects of ganglioside GM1 : implications for Parkinson's disease. J. Pharmacol. Exp. ther. 1992 / 263 (3) / 1440-1446.
(121) Dodel, R.C. et al, Caspase-3-like proteases and 6-hydroxydopamine-induced neuronal cell death. Brain. Res. Mol. Brain. Res. 1999 / 64 (1) / 141-148. , Double, K.L. et al, In vitro studies of ferritin iron release and neurotoxicity. J. Neurochem. 1998 / 70 (6) / 2492-2499.
(122) Javitch, J.A. et al, Parkinsononism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-pyridine : characterization and localization of receptor binding in sites in rat and human brain. Proc. Natl. Acad. Sci. U.S.A. 1984 / 81 (14) / 4591-4595. , Hallman, H. et al, Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse. Eur. J. Pharmacol. 1984 / 97 (1-2) / 133-136.
(123) Irwin, I. et al, Selective accumulation of MPP+ in the substantia nigra : a key to neurotoxicity ? Life Sci. 1985 / 36 (3) / 207-212. , Cohen, G. et al, Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys. Eur. J. Pharmacol. 1984 / 106 (1) / 209-210. , Markey, S.P. et al, Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 1984 / 311 (5985) / 464-467. , Burns, R.S. et al, The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man. Can. J. Neurol. Sci. 1984 / 11 (1 suppl.) / 166-168.
(124) Heikkila, R.E. et al, Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by MAO inhibitors. Nature 1984 / 311 (5985) / 467-469.
(125) Ramsay, R.R. et al, Inhibition of NADH oxidation by pyridine derivates. Biochem. Biophys. Res. Commun. 1987 / 146 (1) / 53-60. , Ansher, S.S. et al, Role of N-methyltransferases in the neurotoxicity associated with the metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and other 4-substituted pyridines present in the environment. Biochem. Pharmacol. 1986 / 35 (19) / 3359-3363.
(126) Deutch, A.Y. et al, 3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system : an animal model of olivopontocerebellar atrophy-associated parkinsonism. Exp. Neurol. 1989 / 105 (1) / 1-9.
(127) Trevor, A.J. et al, Bioactivity of MPTP : reactive metabolites and possible biochemical sequelae. Life Sci. 1987 / 40 (8) / 713-719.
(128) Youngster, S.K. et al, 1-Methyl-4-cyclohexyl-1,2,3,6-tetrahydropyridine (MCTP) : an alicyclic MPTP-like neurotoxin. Neurosci. Lett. 1987 / 79 (1-2) / 151-156.
(129) Kindt, Role for monoamine oxidase-A (MAO-A) in the bioactivation and nigrostriatal dopaminergic neurotoxicity of the MPTP analog, 2'-Me-MPTP. Eur. J. Pharmacol. 1988 / 146 (2-3) / 313-318. , Sonsalla, P.K. et al, Characteristics of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the mouse. J. Pharmacol. Exp. Ther. 1987 / 242 (3) / 850-857.
(130) Heikkila, R.E. et al, Importance of monoamine oxidase in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. U.S.A. 1988 / 85 (16) / 6172-6176.
(131) Youngster, S.K. et al, Evaluation of the biological activity of several analogs of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Neurochem. 1987 / 48 (3) / 929-934.
(132) Finnegan, K.T. et al, 1,2,3,6-tetrahydro-1-methyl-4-(methylpyrrol-2-yl)pyridine : studies on the mechanism of action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Pharmacol. Exp. Ther. 1987 / 242 (3) / 1144-1151.
(133) Chiueh, C.C. et al, Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP : suppression by clorgyline and deprenyl. Synapse 1992 / 11 (4) / 346-348.
(134) Desole, M.S. et al, Correlation between 1-methyl-4-phenylpyridinium (MPP+) levels, ascorbic acid oxidation and glutathione levels in the striatal synaptosomes of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rats. Neurosci. Lett. 1993 / 161 (2) / 121-123.
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Cozinhar Cria Novas Substâncias tóxicas nos alimentos
Adaptado de "Novas Substâncias Em comida preparada" €? por Genriiu Wai
Ver notas de 135 referências científicas!
Cozinhar a comida é sempre gosta de fazer um experimento de química na escola secundária. Devido ao calor, cozinhar ou preparar alimentos cria novas substâncias. A maioria destas novas substâncias vêm de proteínas que reagem com carboidratos. Algumas dessas substâncias causam câncer ou doenças do cérebro e prejudicar a função eo metabolismo dos neurotransmissores.
Muitas dessas novas substâncias são aminas heterocíclicas (HCA). Muitos destes HCA estão direta ou indiretamente dependência física. (1) Devido ao calor do fogo, estes HCA tem origem na interação entre proteínas e hidratos de carbono e / ou creatina (em carnes vermelhas) ou nitratos (em vegetais). Alguns exemplos:
triptofano + / form-acet-aldeído = 1-metil-1 ,2,3,4-tetraidro-beta-carbolina (pró-mutagênicos) (2)
glicoaldeído triptofano + = 1-hidroximetil-tetraidro-beta-carbolina (3)
triptofano + açúcares (por congelação) = 1,1 '-ethyliden ditryptofaan (muito tóxico) (4)
serotonina formol + = 6-hidroxi-tetrahidro-beta-carbolina (5)
serotonina + acetaldeído = 6-hidroxi-1-metil-tetraidro-beta-carbolina (6)
nitrito tiramina + = 3 diazotyramine-(4 - (2-aminoetil))-6-diazo-2 ,4-cyclohexadienone (carcin.) (7)
sal proteinado + nitrito de açúcar / = 2-cloro-4-methylthiobutanoate (mutagénico) (8)
glutamato + açúcar = 2-amino-6-methyldipyrido-(1,2-a: 3 ', 2'-d) imidazol (cancerígeno) (9)
glutamato + açúcar = 2-aminodipyrido-(1,2-a: 3 ', 2'-d) imidazol (cancerígeno) (9)
Quando aldeídos reagem sobre cíclica aminoácidos ou aminas, (como triptofano, triptamina, serotonina, fenilalanina, tirosina, a dopamina, tiramina, anilina), principalmente beta-carbolinas e isoquinolinas originam. Quando a creatinina (de carne) está envolvido, principalmente imidazoquinolines e imidaziquinoxalines originam. (10) (glutamato e triptofano são aminoácidos, tiramina e serotonina são aminas, aldeídos e são os açúcares)
Em Quais os alimentos?
Quase todos os alimentos cozidos ou preparados para conter:
9H-pirido (3,4-b) indol = beta-carbolina triptofano = / triptamina + aldeídos (11)
1-metil-9H-pirido (3,4-b) indol = 1-metil-beta-carbolina = triptofano / triptamina + aldeídos (11)
Estas substâncias influenciam receptores benzodiazepínicos no cérebro e, indirectamente, os lotes de outros neurotransmissores. (12) Se essas novas substâncias reagem sobre aminas como a anilina, eles até se tornar mutagênico (23). Quanto HCA origem depende da quantidade de proteína que o alimento contém e sobre o quanto a comida é aquecida. (14) Porque a carne vermelha contém muita proteína e creatinina (criação de creatina), a carne vermelha contém o mais preparado HCA, especialmente quando grelhado (15). Além de carne vermelha preparada, também preparado de soja, peixes e aves contêm grande quantidade de HCA. (16) Sabor-enhancers eo caldo de carne contém proteína de concentrados e, portanto, contêm grande quantidade de HCA também. (11) Mas também alimentos preparados que contêm menos proteínas contêm HCA, como grãos preparados (17) e dos produtos hortícolas (18), e até mesmo alimentos como a cerveja, molho de soja e suco de laranja enlatado. (19) Por exemplo:
A carne contém muita creatina (20):
2-amino-1-metil-6-(4 hydroxyfenyl) imidazo-(4,5-b) piridina (mutag.) = tirosina + creatina + glicose (21)
A soja contém globulinas:
2-amino-9H-pirido-(2,3-b) indol (mutagénico) (22) =-globulinas de soja + açúcar (23)
2-amino-3-metil-9H-pirido-(2,3-b) indol (mutagénico) (24) =-globulinas de soja + açúcar (23)
peixes preparados contém (25):
3-amino-1 ,4-dimetil-5H-pirido (4,3-b) indol (mutagénico) (26) = triptofano acetaldeído + (27)
3-amino-1-metil-5H-pirido (4,3-b) indol (mutagénico) (26) = + triptofano acetaldeído (28)
Legumes cozidos contém nitrito:
cancerosas N-nitroso-compostos aminas = + + nitrito açúcares
específicos compostos N-nitrosos;
4 - (2-aminoetil)-6-diazo-2 ,4-cyclohexadienone (cancerosos) tiramina = + + nitrito açúcares (7)
Cozido Couves conter tiocianatos;
tóxicos (29) tetraidro-beta-carbolina-derivados de isotiocianato de tiramina = + / serotonina etc
legumes cozidos também contêm flavonóides:
glicosídeos mutagênico (30) flavonods = + calor
Conservas de suco de laranja contém aminoácidos livres, que combinam facilmente com aldeídos para criar aminas heterocíclicas.
O que pode fazer HCA?
1. Agir como neurotransmissores
Alguns ACS, como beta-carbolinas, pode influenciar diretamente os receptores do neurotransmissor, como os receptores de benzodiazepínicos. Simplesmente porque o corpo também compõe betacarbolinas funcionar como neurotransmissores. HCA também pode ocupar os receptores de outros neurotransmissores, como receptores de serotonina, a dopamina ea. Especialmente quando eles são compostos de aminas mesmo. Alguns exemplos;
actos de 3 metoxicarbonil-beta-carbolina através de receptores diferentes (31) e aumenta a secreção de dopamina e decomposição, como o estresse físico faz. (32) melhora o comportamento "irracional" agressiva (33), e diminui a interação social (34).
3-ethoxycarbonyl-beta-carbolina, é hipnótico e anestésico (35), e inibe o comportamento de investigação (36) e interação social. (37) Na tipos dominantes, reforça o comportamento agressivo, mas inibe o apetite sexual. (38) Aumenta a adrenalina (39) e nível de cortisol, pressão arterial e freqüência cardíaca (40), e secreção aumenta e decomposição de dopamina (41), como o estresse físico faz.
3-hidroximetil-beta carbolina, embora hipnótica (42), ela afeta negativamente o sono (43).
3-N-methylcarboxamide-beta-carbolina aumenta imprudente comportamento de (44) e agressiva (45), e inibe o apetite sexual. (46) É geralmente inibe (47), mas localmente estimula a secreção de noradrenalina. (48) Aumenta-glutamato (49), ACTH e secreção de substância P (50), aumenta a pressão arterial (51) e, apesar de anestesia (52), provoca estresse físico. (53).
3-Methylcarbonyl-6 ,7-dimetoxi-4-etil-beta-carbolina bloqueia os receptores GABA (54), aumenta o GABA e nível de glicina, glutamato e diminui o nível de aspartato (55), os aumentos de corticosterona, epinefrina e secreção de noradrenalina (56), diminui a secreção de serotonina, (57) e aumenta a noradrenalina-receptor de actividade. (58) aumenta o efeito da cocaína (59), causa ansiedade (60) e suprime a atividade do sistema imunológico. (61)
3-Ethylcarbonyl-6-benziloxi-4-methoxymethyl beta-carbolina é sedativo (62), causa amnésia (63) e blocos de beta-estradiol, LH (hormônio luteinizante) interação. (64)
3-Ethylcarbonyl-5-benziloxi-4-methoxymethyl-beta-carbolina estimula fortemente o apetite. (65)
3-Ethylcarbonyl-5-isopropil-4-metil-beta-carbolina inquietação causas (66), insônia (67), e diminui a interação social. (68)
Além de 'normal' beta-carbolinas, alimentos preparados também contêm tetraidro-beta-carbolinas. (69).
Tetraidro-beta-carbolina estimula a compulsão pelo álcool (70), aumenta a freqüência cardíaca e pressão arterial (71) e, como 5-metoxi-tetraidro-beta-carbolina e aumenta 5-hidroxi-tetrahidro-beta-carbolina nível de prolactina e afeta receptores de serotonina. (72)
aumenta 6-metóxi-tetraidro-beta-carbolina da noradrenalina e da secreção de ACTH e diminuição de serotonina e secreção do hormônio do crescimento. (73)
2-Fenylpyrazolo (4,3-c) quinolina-3 (5H)-é um sedativo (74), aumenta nível de corticosterona (75) e diminui específicas benzodiazepina-receptores no cérebro. (76)
2. Porque o cancro
Parte do processo que causa câncer é Mutagénica danificar o DNA celular. (Ver Site5) Alguns HCA em alimentos preparados são os aumentos dos danos mutagenic.DNA linearmente com a ingestão de HCA. (77) Como são cancerígenos HCA é parcialmente dependente da quantidade de nitrogênio que contêm. (78) de sal, proteínas e nitrito (a partir de vegetais) pode fornecer nitrogênio ao reagir sobre HCA. E HCA nitrosados são ainda mais cancerígenos. (79) Alguns dos HCA mais difundida mutagênicos em alimentos preparados são:
pyridoindole (80) (amino-gama-carbolina)
2-amino-9H-pirido-(2,3-b) indol (81) (amino-alfa-carbolina)
2-amino-3-metil-9H-pirido-(2,3-b) (82)
3-amino-1 ,4-dimetil-5H-pirido (4,3-b) indol (83)
3-amino-1-metil-5H-pirido (4,3-b) indol (84)
1-metil-3-carbonil-1 ,2,3,4-tetraidro-beta-carbolina (85).
4-Aminobifenilo (86)
4,4 'Metilenodianilina (87)
3,2 '-dimetil-4-Aminobifenilo (88)
1,2-dimetil (89)
hidroxilamina-fenil (90)
O-acetil-N-(5-fenil-2-piridil)-hidroxilamina (91)
2-amino-3-methylimidazo (4,5-f) quinoleína (92)
2-amino-3-methylimidazo (4,5-f) quinoxalina (93)
2-amino-3 ,4-dimethylimidazo (4,5-f) quinoleína (94)
2-amino-3 ,8-dimethylimidazo (4,5-f) quinoxalina (95)
2-amino-3 ,4,8-trimethylimidazo (4,5-b) piridina (96)
2-amino-3 ,4,8-trimethylimidazo (4,5-f) quinoxalina (97)
2-amino-3 ,7,8-trimethylimidazo (4,5-f)-quinoxalina (98)
2-amino-n, n, n-trimethylimidazo-piridina (99)
2-N-amino, dimethylimidazopyridine n (100)
2-amino-4-hidroximetil-3 ,8-dimethylimidazo (4,5 g)-quinoxalina (101)
2-amino-1 ,7,9-trimethylimidazo (4,5 g)-quinoxalina (101)
2-amino-1-metil-6-phenylimidazo-(4,5-b)-piridina (102)
3. Encefalopatias Causa
Alguns ACS são diretamente tóxicas para o cérebro, como quinolinas comum, que entra no cérebro através do sistema de transporte de dopamina. (103) Outros HCA comum (como piridinas (104) e beta-carbolinas (105)) só se torna tóxico para o cérebro depois de terem sido parcialmente decomposto por enzimas diferentes (106) no corpo. Originalmente, estas enzimas têm de, e não proteger o cérebro contra substâncias tóxicas, mas parte dos ACS são acidentalmente transformado em substâncias mais tóxicas. (107) Obviamente, a natureza não contava com HCA "estranho" do alimento preparado. Piridinas só podem ocupar os receptores de dopamina (108) e, portanto, são tóxicas para thesereceptors só. Parcialmente decompostos piridinas são mais tóxicos do que os originais (109), mas os originais não-redução da dopamina (110), norepinefrina (111) e principalmente a nível de serotonina (112). A destruição dos receptores no cérebro provoca doenças como o cérebro Alzheimerâ s ™ €, € ™ s Parkinsonâ e esquizofrenia. Alguns tóxicos para o HCA-cérebro são:
3-N-butylcarbonyl-beta-carbolina (113)
3-N-methylcarboxamide-beta-carbolina (113)
2-metil-1 ,2,3,4-tetraidro-beta-carbolina (114)
2-metil-1 ,2,3,4-tetrahidro-isoquinolina (114)
quinolinate (115)
quisqualinate (116)
tetraidroisoquinolina (117)
1-benzil-tetrahidro-isoquinolina (117)
N-metil-(R)-salsolinol (118)
N-metil-6-metoxi-1 ,2,3,4-tetrahidro-isoquinolina (119)
6-metoxi-1 ,2,3,4-tetrahidro-isoquinolina (119)
2,4,5-trihydroxyphenylalanine (120)
6-hidroxi-dopamina (121)
N-metil-4-fenyl-1 ,2,3,6-tetraidropiridina (122)
1-metil-4-fenyl-1 ,2,3,6-tetraidropiridina (123)
1-metil-4-fenyl-1 ,2,5,6-tetraidropiridina (124).
4-fenyl-1 ,2,3,6-tetraidropiridina (125)
4-fenylpyridine (125)
3-acetilpiridina (126)
1-metil-4-fenil-1 ,4-dihidropiridinas (127)
1-metil-4-cyclohexic-1 ,2,3,6-tetraidropiridina (128)
1-metil-4-(2'-methylfenyl) -1,2,3,6 - tetraidropiridina (129)
1-metil-4-(2'-ethylfenyl) -1,2,3,6-tetraidropiridina (130)
1-metil-4-(3'-methoxyfenyl) -1,2,3,6-tetraidropiridina (131)
1-metil-4-(methylpyrrol-2-il) -1,2,3,6-tetraidropiridina (132)
Embora piridinas tóxicos criar radicais oxidativos (133) e diminuir o nível de antioxidantes (134), a ingestão de antioxidantes não pode impedir os danos cerebrais por piridinas tóxicos. (135)
Aditivos
preparação de alimentos é sobretudo lá para fazer comestíveis que não é tão comestíveis. Os aditivos são primeiramente lá para fazer a comida durar mais falso, e fazer você comer mais. potenciadores de sabor, por exemplo, estão mais concentrados de proteína, repleta de dependência física beta-carbolinas que fazem você comer mais. O glutamato (popular na cozinha chinesa) influi diretamente na mesma (benzodiazepina) receptores.
Notas de Rodapé
Resumos da maioria das fontes podem ser encontradas na Biblioteca Nacional de Medicina
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