Histamine intolerance and genetics

[Who Me?]

Thanks If you're going to talk to me about that you really need to dumb it down. That's way beyond me on a good day, but I get the gist of what you are saying.

 

[Issie]

Thanks If you're going to talk to me about that you really need to dumb it down. That's way beyond me on a good day, but I get the gist of what you are saying.

Lol, I did. I'll try to be simplier.
Bottom line. Stopping mast cells from exploding their content will help you to have less pain.
Issie

 

[Who Me?]

Lol, I did. I'll try to be simplier.
Bottom line. Stopping mast cells from exploding their content will help you to have less pain.
Issie

Excellent! Seriously, I tested at a 4th grade level a few years ago.

 

[Lissa]

@Veet I'm looking at mine now, low DAO.

I do have the same one as you! Sister's from a different mister!

Do you have ideas for boosting Dao besides $$$ Dao stuff?


HNMT 138771760 rs1050891 A or G
AA



ABP1 150554553 rs1049742 C or T
CT

My results:
rs1050891 = AA
rs10156191 =TT

and the other 2 were normal...
did not find rs11558538 (or i300469) for some reason. Neither showing up on 23&me. (Does that mean I don't have them? yay? Or does 23&me not do them?)

I presume that this confirms a histamine problem. So far I have felt better taking the H1/H2 blockers for the past 3 weeks. Curious now about adding DAO, and/or stuff like the NeuroProtek, Quercitin etc. (I have another couple weeks till my next ND appointment, and he's learning as we go, just like I am.)

Also wondering about adjusting diet (yet again... siggghhh). So far I have thrown caution to the wind a bit (and "a BIT" means that literally -- still mostly Paleo) as to what I am eating --- I'd rather know for sure that the H1/H2s are working rather than to have shifted the diet to low histamine, and be wondering which was responsible for better/worse. But it seems to stand to reason that if indeed there IS a histamine &/or Mast Cell Activation problem -- wouldn't eating low histamine make the most sense?

I've almost finished Afrin's (MCAS) book -- and he seems to not want to focus on diet much --- as it seems to be so different from person to person. So I am now grappling with what to tackle next. More pills to thrown down the gullet -- DAO? Mast Cell calmers? Both?, or buckle down on another new diet plan? Or do it all -- carefully adding one change at a time? It makes me tired just thinking about it....

 

[Who Me?]

I didn't have some genes either

I'm having good luck with mangosteen when I eat something I shouldn't. I also ordered some daosin so I should be cured.

Also neuroprotek seems to be helping more than quercetin and rutin separately although they helped.

I've adjusted my diet some but I can't do pales cuz of my IBS c.

Dao is supposed to help when you eat something bad so maybe experiment with that before cutting out food.

Forgot what else I was gonna say. Oh. It taking an h2 thing but overall lots of some crazy symptoms, like feeling like someone was jamming their fingers in my boobs is gone. And some other gut pain things.

If uku decide on neuroprotek If you buy from the place argonot? It's more but you can return it in 30 days. I got it from a place with free shipping since I knew I could take all the ingredients.

 

[Remy]

DAO uses FAD as a cofactor

MAO uses FAD as a cofactor...DAO uses B6, B12 and copper and iron.

[bimg=no-lightbox]http://suzycohen.com/wp-content/uploads/2015/10/Screen-Shot-2015-10-17-at-2.45.58-PM.png[/bimg]

 

[Remy]

Sorry. Suzy is not using the current gene name for Amiloride-sensitive amine oxidase (also called (Diamine oxidase) so I looked up the wrong gene and failed to check my work. But B6 is still not a cofactor. I knew this because of biochemistry and B6 in any form cannot serve in oxidase reactions because electrons.

Here is the Diamine Oxidase gene:
http://www.uniprot.org/uniprot/P19801

It used to be called DAO1 but now it is called AOC1 and it can use copper, calcium, and topoquinone as cofactors.

I am being specific as to use of the term cofactor. AOC1 does not use B12, iron, or B6 as a cofactor.

I think we both learned a lesson: double check your work!

http://www.ncbi.nlm.nih.gov/pubmed/8645981?dopt=Abstract

http://ajcn.nutrition.org/content/85/5/1185.long#ref-14

I'm still pretty sure B6 is a cofactor of DAO, as the term is *commonly* used.

 

[RuthAnn]

Taking B6 will increase AOCS1 activity only because it will make more histamine by stimulating histamine decarboxylase.

That is not the same as it being a cofactor and increasing the enzymatic activity.

http://www.uniprot.org/uniprot/P19113

B6 is the cofactor for HDC. So if you have histamine intolerance it will only make your allergies worse because it will increase its enzymatic activity and turn more histadine into histamine.

This is why you need to be careful interpriting the research.

Very interesting. I looked all over the place to see why it is "commonly said" that B6 helps DAO and couldn't find anything.

From the link:

Protein
Histidine decarboxylase
Gene
HDC
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:-Experimental evidence at protein leveli
Functioni

Catalyzes the biosynthesis of histamine from histidine.1 Publication
Catalytic activityi

L-histidine = histamine + CO2.1 Publication
Cofactori

pyridoxal 5'-phosphate1 Publication

 

[Remy]

And all I had to do was consult the Textbook of Medical Biochemistry, 8th edition.

Sorry you wasted your time, @RuthAnn, when it's so easy to find.

 

[RuthAnn]

And all I had to do was consult the Textbook of Medical Biochemistry, 8th edition.

Sorry you wasted your time, @RuthAnn, when it's so easy to find.

View attachment 1703

So let me see if I have this straight.

Is the B6-P a cofactor of DAO?

Or does it represent a coenzyme, histidine decarboxylase?

https://en.wikipedia.org/wiki/Histidine_decarboxylase

 

[Remy]

So let me see if I have this straight.

Is the B6-P a cofactor of DAO?

Or does it represent a coenzyme, histidine decarboxylase?

https://en.wikipedia.org/wiki/Histidine_decarboxylase

Histidine to histamine and histamine to b-imidazole acetaldehyde are two different reactions and they both require B6 as a cofactor.

The former uses histidine decarboxylase and the latter uses DAO.

 

[RuthAnn]

Since this thread is called histamine and genetics, I looked up the genetics of DAO and found this.

http://www.genome.jp/dbget-bin/www_bget?enzyme+1.4.3.22

Then I looked up the genetics for histidine decarboxylase and found this:

http://www.genome.jp/dbget-bin/www_bget?enzyme+4.1.1.22

So I see that histidine decarboxylase is an enzyme that is built around B6. And it's called a coenzyme, don't see the word cofactor.

I don't see anything in DAO that mentions B6. I guess I should look in the pathway.

 

[RuthAnn]

Well, I'll copy the stuff here and you can show me where the B6 comes in.

It's funny, because for a couple of years now I have seen that DAO is made up of copper and B6. As if it were a fact!

Entry
EC 1.4.3.22 Enzyme​

​

Name​

diamine oxidase;
amine oxidase (ambiguous);
amine oxidase (copper-containing) (ambiguous);
CAO (ambiguous);
Cu-containing amine oxidase (ambiguous);
copper amine oxidase (ambiguous);
diamine oxidase (ambiguous);
diamino oxhydrase (ambiguous);
histaminase;
histamine deaminase (incorrect);
semicarbazide-sensitive amine oxidase (incorrect);
SSAO (incorrect)

Class​

Oxidoreductases;
Acting on the CH-NH2 group of donors;
With oxygen as acceptor

Sysname​

histaminexygen oxidoreductase (deaminating)

Reaction(IUBMB)​

histamine + H2O + O2 = (imidazol-4-yl)acetaldehyde + NH3 + H2O2 [RN:R02150]

Reaction(KEGG)​

R02150;
(other) R01151 R02173 R03139 R04674 R06133

Substrate​

histamine [CPD:C00388];
H2O [CPD:C00001];
O2 [CPD:C00007]

Product​

(imidazol-4-yl)acetaldehyde;
NH3 [CPD:C00014];
H2O2 [CPD:C00027]

Comment​

A group of enzymes that oxidize diamines, such as histamine, and also some primary monoamines but have little or no activity towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, like EC 1.4.3.21 (primary-amine oxidase) but unlike EC 1.4.3.4 (monoamine oxidase), they are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide.

History​

EC 1.4.3.22 created 2007 (EC 1.4.3.6 created 1961, part-incorporated 2008)

Pathway​

ec00330

Arginine and proline metabolism

ec00340

Histidine metabolism

ec00380

Tryptophan metabolism

ec01100

Metabolic pathways
Orthology​

K11182

diamine oxidase
Genes​

HSA:

26(AOC1)

PTR:

463895(AOC1)

PPS:

100973977(AOC1)

GGO:

101145709(ABP1)

PON:

100173768(AOC1)

NLE:

100598250(AOC1)

MCC:

714112(AOC1)

MCF:

102141942(AOC1)

RRO:

104675391(AOC1)

CJC:

100414302(AOC1)
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» show all

Reference​

1

Authors​

Zeller, E.A.

Title​

Diamine oxidases.

Journal​

In: Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 8, Academic Press, New York, 1963, p. 313-335.

Reference​

2 [PMID:182134]

Authors​

Crabbe MJ, Waight RD, Bardsley WG, Barker RW, Kelly ID, Knowles PF.

Title​

Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity.

Journal​

Biochem. J. 155 (1976) 679-87.

Reference​

3 [PMID:8182053]

Authors​

Chassande O, Renard S, Barbry P, Lazdunski M.

Title​

The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter.

Journal​

J. Biol. Chem. 269 (1994) 14484-9.

Sequence​

[hsa:26]

Reference​

4 [PMID:10668504]

Authors​

Houen G.

Title​

Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions.

Journal​

APMIS. Suppl. 96 (1999) 1-46.

Reference​

5 [PMID:12072962]

Authors​

Elmore BO, Bollinger JA, Dooley DM.

Title​

Human kidney diamine oxidase: heterologous expression, purification, and characterization.

Journal​

J. Biol. Inorg. Chem. 7 (2002) 565-79.

Other DBs​

ExplorEnz - The Enzyme Database:
1.4.3.22
IUBMB Enzyme Nomenclature:
1.4.3.22
ExPASy - ENZYME nomenclature database:
1.4.3.22
BRENDA, the Enzyme Database:
1.4.3.22

All links
Pathway (8)
KEGG PATHWAY (8)
Chemical substance (16)
KEGG COMPOUND (16)
Chemical reaction (25)
KEGG REACTION (6)
KEGG RPAIR (18)
KEGG RCLASS (1)
Gene (142)
KEGG ORTHOLOGY (1)
KEGG GENES (96)
KEGG DGENES (10)
KEGG MGENES (21)
RefGene (5)
EGENES (9)
Protein sequence (57)
UniProt (31)
SWISS-PROT (6)
RefSeq(pep) (11)
PDBSTR (9)
DNA sequence (40)
RefSeq(nuc) (18)
GenBank (13)
EMBL (9)
3D Structure (5)
PDB (5)
Literature (4)
PubMed (4)
All databases (297)

Download RDF
DBGET integrated database retrieval system

 

[Remy]

Well, I'll copy the stuff here and you can show me where the B6 comes in.

It's funny, because for a couple of years now I have seen that DAO is made up of copper and B6. As if it were a fact!

Entry
EC 1.4.3.22 Enzyme​

​

Name​

diamine oxidase;
amine oxidase (ambiguous);
amine oxidase (copper-containing) (ambiguous);
CAO (ambiguous);
Cu-containing amine oxidase (ambiguous);
copper amine oxidase (ambiguous);
diamine oxidase (ambiguous);
diamino oxhydrase (ambiguous);
histaminase;
histamine deaminase (incorrect);
semicarbazide-sensitive amine oxidase (incorrect);
SSAO (incorrect)

Class​

Oxidoreductases;
Acting on the CH-NH2 group of donors;
With oxygen as acceptor

Sysname​

histaminexygen oxidoreductase (deaminating)

Reaction(IUBMB)​

histamine + H2O + O2 = (imidazol-4-yl)acetaldehyde + NH3 + H2O2 [RN:R02150]

Reaction(KEGG)​

R02150;
(other) R01151 R02173 R03139 R04674 R06133

Substrate​

histamine [CPD:C00388];
H2O [CPD:C00001];
O2 [CPD:C00007]

Product​

(imidazol-4-yl)acetaldehyde;
NH3 [CPD:C00014];
H2O2 [CPD:C00027]

Comment​

A group of enzymes that oxidize diamines, such as histamine, and also some primary monoamines but have little or no activity towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, like EC 1.4.3.21 (primary-amine oxidase) but unlike EC 1.4.3.4 (monoamine oxidase), they are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide.

History​

EC 1.4.3.22 created 2007 (EC 1.4.3.6 created 1961, part-incorporated 2008)

Pathway

ec00330

Arginine and proline metabolism

ec00340

Histidine metabolism

ec00380

Tryptophan metabolism

ec01100

Metabolic pathways
Orthology

K11182

diamine oxidase
Genes

HSA:

26(AOC1)

PTR:

463895(AOC1)

PPS:

100973977(AOC1)

GGO:

101145709(ABP1)

PON:

100173768(AOC1)

NLE:

100598250(AOC1)

MCC:

714112(AOC1)

MCF:

102141942(AOC1)

RRO:

104675391(AOC1)

CJC:

100414302(AOC1)













































































































​

» show all

Reference​

1

Authors​

Zeller, E.A.

Title​

Diamine oxidases.

Journal​

In: Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 8, Academic Press, New York, 1963, p. 313-335.

Reference​

2 [PMID:182134]

Authors​

Crabbe MJ, Waight RD, Bardsley WG, Barker RW, Kelly ID, Knowles PF.

Title​

Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity.

Journal​

Biochem. J. 155 (1976) 679-87.

Reference​

3 [PMID:8182053]

Authors​

Chassande O, Renard S, Barbry P, Lazdunski M.

Title​

The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter.

Journal​

J. Biol. Chem. 269 (1994) 14484-9.

Sequence​

[hsa:26]

Reference​

4 [PMID:10668504]

Authors​

Houen G.

Title​

Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions.

Journal​

APMIS. Suppl. 96 (1999) 1-46.

Reference​

5 [PMID:12072962]

Authors​

Elmore BO, Bollinger JA, Dooley DM.

Title​

Human kidney diamine oxidase: heterologous expression, purification, and characterization.

Journal​

J. Biol. Inorg. Chem. 7 (2002) 565-79.

Other DBs​

ExplorEnz - The Enzyme Database:
1.4.3.22
IUBMB Enzyme Nomenclature:
1.4.3.22
ExPASy - ENZYME nomenclature database:
1.4.3.22
BRENDA, the Enzyme Database:
1.4.3.22

All links
Pathway (8)
KEGG PATHWAY (8)
Chemical substance (16)
KEGG COMPOUND (16)
Chemical reaction (25)
KEGG REACTION (6)
KEGG RPAIR (18)
KEGG RCLASS (1)
Gene (142)
KEGG ORTHOLOGY (1)
KEGG GENES (96)
KEGG DGENES (10)
KEGG MGENES (21)
RefGene (5)
EGENES (9)
Protein sequence (57)
UniProt (31)
SWISS-PROT (6)
RefSeq(pep) (11)
PDBSTR (9)
DNA sequence (40)
RefSeq(nuc) (18)
GenBank (13)
EMBL (9)
3D Structure (5)
PDB (5)
Literature (4)
PubMed (4)
All databases (297)

Download RDF
DBGET integrated database retrieval system

Refer to my earlier post. It's very clear where the B6 comes in.

DAO isn't "made up" of B6. It uses it.

 

[RuthAnn]

Refer to my earlier post. It's very clear where the B6 comes in.

DAO isn't "made up" of B6. It uses it.

Oh wait, here's the reaction from KEGG:
Where's the B6?

Reaction:

Entry
R02150 Reaction​

​

Name​

1H-Imidazole-4-ethanaminexygen oxidoreductase (deaminating) (copper-containing)

Definition​

Histamine + Oxygen + H2O <=> Imidazole-4-acetaldehyde + Ammonia + Hydrogen peroxide

Equation​

C00388 + C00007 + C00001 <=> C05130 + C00014 + C00027

​

RPair​

RP00006

C00007_C00027 cofac [RC:RC02755]

RP02002

C00388_C05130 main [RC:RC00062]

RP06869

C00001_C05130 leave

RP06870

C00014_C00388 leave
Enzyme​

1.4.3.22

Pathway​

rn00340

Histidine metabolism
Orthology​

K11182

diamine oxidase [EC:1.4.3.22]​

 

[Remy]

It's covalently linked to the diamine oxidase.

Anal Biochem. 1994 Jul;220(1):185-91.
Isolation and identification by gas chromatographic mass spectrometry of the carbonyl-active site of pig kidney diamine oxidase.

Buffoni F1.
Author information


Erratum in

• Anal Biochem 1994 Nov 1;222(2):520.

Abstract

An adduct with phenylhydrazine was formed with the purified pig kidney diamine oxidase and in parallel with the l-tyrosine decarboxylase from Streptococcus faecalis. The labeled enzymes were hydrolyzed by chemical hydrolysis and the adducts released by hydrolysis were isolated and identified first in HPLC and successively in GC-MS. Both enzymes gave the same adduct which was identified as the phenylhydrazone of pyridoxal. The isolated adduct had the same retention time as the phenylhydrazone of pyridoxal in HPLC and in gas chromatography and showed the same molecular weight in mass spectrometry when chemical ionization was used and the same fragmentation in mass spectrometry when electronic impact was used. The reported results show that pig kidney diamine oxidase contains pyridoxal in the form of covalently linked pyridoxal phosphate which can be released from the enzyme only by chemical hydrolysis. Pig kidney diamine oxidase is therefore a pyridoxal enzyme such as l-tyrosine decarboxylase as hypothesized in the past but never clearly demonstrated.

That linkage forms a cyclic compound.

http://www.ncbi.nlm.nih.gov/pubmed/7246346
Agents Actions. 1981 Apr;11(1-2):28-32.
In vivo formation of histamine phosphopyridoxal cyclic compounds.

Kierska D, Sasiak K, Maśliński C.
Abstract

A possibility of in vivo formation of cyclic compounds between histamine (Hi) given i.p. and endogenous pyridoxal (PL) or pyridoxal 5'-phosphate (PLP) has been studied. Cyclic compounds of Hi with PL or PLP were found in all tissues examined. Although an increase in Hi levels in tissues enhances the formation of cyclic compounds, no simple relationship between the rate of formation and Hi concentration has been observed. The reaction seems to be limited by endogenous PLP. The cyclic products Hi-PL and Hi-PLP were discovered in urine. It is suggested that the process of cyclic compound formation may reduce PLP resources, resulting in a modification of PLP-enzyme activities.



http://www.ncbi.nlm.nih.gov/pubmed/102131

Agents Actions. 1978 Oct;8(5):470-3.
Phosphopyridoxal cyclic compounds with histamine and histidine. 6: The formation of phosphopyridoxal cyclic compounds with histamine and histidine in the presence of biological material.

Kierska D, Sasiak K, Maśliński C.
Abstract

We have studied the dynamics of cyclic compound formation between histamine or histidine and pyridoxal 5'-phosphate (Hi-PLP or His-PLP) in incubates of rat gastric mucosa histidine decarboxylase (HD), rat intestinal diamine oxidase (DAO) or homogenates of either rat liver, intestine or gastric mucosa. For gastric mucosa HD, liver and gastric mucosa homogenates, the rate of cyclization was slightly decreased; however, the rate was significantly inhibited with intestinal DAO or intestinal homogenate. Binding of PLP by tissue components was measured; free PLP was bound abundantly by rat intestinal DAO and by rat intestinal homogenate. A possible mechanism by which intestinal tissues inhibit cyclic compound formation is discussed.

http://www.ncbi.nlm.nih.gov/pubmed/3426767

And when you give B6, histamine levels are normalized because the enzymes are bunk without it.

Alcohol Alcohol. 1987;22(4):389-94.
Influence of pyridoxal 5'-phosphate on ethanol-induced changes in histamine catabolism in the guinea pig.

Kierska D1, Sasiak K, Maslinski C.
Author information


Abstract

In guinea pigs, chronic intragastric administration of a 20% ethanol solution for 18 days (in increasing doses from 5 to 10 g/kg/day) leads, on the 18th day, to an enhancement of histamine level in the liver and the small intestine by up to 170% and 180% respectively. In these tissues the rate of histamine oxidative catabolism was depressed by about 20%. Histamine N-methyltransferase activity, as well as the level of acetylhistamine were not affected. Pyridoxal 5'-phosphate (2 mg/animal/day) tended to normalize both histamine levels and the rate of histamine oxidative catabolism.

Just like they described all along.

 

[RuthAnn]

It's covalently linked to the diamine oxidase.


That linkage forms a cyclic compound.

http://www.ncbi.nlm.nih.gov/pubmed/7246346
Agents Actions. 1981 Apr;11(1-2):28-32.
In vivo formation of histamine phosphopyridoxal cyclic compounds.

Kierska D, Sasiak K, Maśliński C.
Abstract

A possibility of in vivo formation of cyclic compounds between histamine (Hi) given i.p. and endogenous pyridoxal (PL) or pyridoxal 5'-phosphate (PLP) has been studied. Cyclic compounds of Hi with PL or PLP were found in all tissues examined. Although an increase in Hi levels in tissues enhances the formation of cyclic compounds, no simple relationship between the rate of formation and Hi concentration has been observed. The reaction seems to be limited by endogenous PLP. The cyclic products Hi-PL and Hi-PLP were discovered in urine. It is suggested that the process of cyclic compound formation may reduce PLP resources, resulting in a modification of PLP-enzyme activities.



http://www.ncbi.nlm.nih.gov/pubmed/102131

Agents Actions. 1978 Oct;8(5):470-3.
Phosphopyridoxal cyclic compounds with histamine and histidine. 6: The formation of phosphopyridoxal cyclic compounds with histamine and histidine in the presence of biological material.

Kierska D, Sasiak K, Maśliński C.
Abstract

We have studied the dynamics of cyclic compound formation between histamine or histidine and pyridoxal 5'-phosphate (Hi-PLP or His-PLP) in incubates of rat gastric mucosa histidine decarboxylase (HD), rat intestinal diamine oxidase (DAO) or homogenates of either rat liver, intestine or gastric mucosa. For gastric mucosa HD, liver and gastric mucosa homogenates, the rate of cyclization was slightly decreased; however, the rate was significantly inhibited with intestinal DAO or intestinal homogenate. Binding of PLP by tissue components was measured; free PLP was bound abundantly by rat intestinal DAO and by rat intestinal homogenate. A possible mechanism by which intestinal tissues inhibit cyclic compound formation is discussed.

http://www.ncbi.nlm.nih.gov/pubmed/3426767
​

That linkage forms a cyclic compound.




And when you give B6, histamine levels are normalized because the enzymes are bunk without it.



Just like they described all along.

That linkage is a compound of histamine and a pyridoxal compound found in urine. What does that have to do with DAO or how does it prove that B6 is a cofactor of DAO?

 

[Yavapai]

That linkage is a compound of histamine and a pyridoxal compound found in urine. What does that have to do with DAO or how does it prove that B6 is a cofactor of DAO?

Good question.

 

[Remy]

That linkage is a compound of histamine and a pyridoxal compound found in urine. What does that have to do with DAO or how does it prove that B6 is a cofactor of DAO?

First link. Pyridoxal enzyme means B6.

 

[Remy]