A report about anti-glycation supps Carnosine Beta-Alanine (=methylation?)

[Gondwanaland]

Could it be why carcinine gives us nails that tear easily?

I read somewhere that poor nail health can be due to low stomach acid. I think it is possible that Carnosine/Carcinine would lower stomach acid: it buffers acidity in body + uses up B1.

 

[Asklipia]

I read somewhere that poor nail health can be due to low stomach acid. I think it is possible that Carnosine/Carcinine would lower stomach acid: it buffers acidity in body + uses up B1.

We have not felt any digestion problems.

 

[Gondwanaland]

my magnesium levels are even too high.

My uric acid is low

B1 made everything so much better until it stopped working

polyuria and thirst

Have you ever tried Molybdenum? While I can't tolerate Moly supps very well, eating chick peas does wonders for my sulfur metabolism.

At one point I would get gouty symptoms from eating chick peas, but then I took so many measures to lower uric acid that I ended up antagonizing Molybdenum too much. Now I can only sleep if I eat chick peas... Digestion of animal protein and sulfury vegetables is much improved.

Taking MSM for instance was giving me hyperglycemia, and high Moly foods (legumes) are known to normalize blood sugar.

http://www.acu-cell.com/vmo.html

http://whfoods.org/genpage.php?tname=nutrient&dbid=128

http://lpi.oregonstate.edu/mic/minerals/molybdenum

https://examine.com/supplements/molybdenum/

http://www.healthsupplementsnutritionalguide.com/molybdenum/

http://healthandscience.eu/index.ph...490:molybdenum-mo&catid=54&Itemid=327&lang=en

 

[NotThisGuy]

@Gondwanaland
I have more problems with beeing hypoglycemic. not by blood panel but I have to snack every hour.

i tried molybdenum twice.
molybdenum bound to sodium made me very anemic and molybdenumglycinate didnt do much at all.
allthough my hair test and blood test showed that my molybdenum is on the lower side (still in reference range though)

basically im still sitting here and waiting until im ready to take liquid b12 with other b vitamin again.
At least in the past I believe that solved my intolerance to everything... but not 100% if it was that...

after that I will give molybdenum another shot

 

[Gondwanaland]

I have more problems with beeing hypoglycemic. not by blood panel but I have to snack every hour.

i tried molybdenum twice.
molybdenum bound to sodium made me very anemic and molybdenumglycinate didnt do much at all.
allthough my hair test and blood test showed that my molybdenum is on the lower side (still in reference range though)

Interesting. I have a few scattered notes waiting to be put together about Moly:

• Moly + beta-carotene + vit C = endogenous vit A ; increased endogenous Taurine ; increased endogenous Melatonin
• Moly is high in the blood of diabetics, interestingly someone close to me likely had this feature from eating high Moly foods (kidney stones), started having extreme sulfur intolerance (hated garlic smell all of a sudden) and then was diagnosed as diabetic. I think vit D/B6 deficiency.
• Moly needs Zinc to transport vit A with iron from the liver to build new RBCs (ideal copper status is needed because Mo and Cu are antagonists)
• Moly forms Molybdopterins needed to recycle 4HBiopterin

The known enzymes to which Moly is a co-factor are

• aldehyde oxidase - needs ...... ?Zinc citrate, B1, B3, B5, B6, vit C, NAC, GLA, ALipoicA, Silymarin? .....
• sulfite oxidase - needs ?B1, B6? .....
• xanthine oxidase - needs folate, B2, lecithin, glycine (methyl donors like DMG, TMG), vit A (B-carotene + vit C, and possibly B5 and B6 will avoid excess uric acid and kidney stones)
• mitochondrial amidoxime reducing component - needs ......

Molybdenum is HIGHLY needed when taking carcinine because it will make AO and SO work optimally.

Any input about Moly is highly appreciated ( @alicec ?)

 

[alicec]

I don't know a lot about molybdenum.

It is readily absorbed from the gut and carried in the blood in the molybdate form bound to alpha–macroglobulin and by adsorption to red blood cells.

Mobydate is taken up into cells and used to form the molybdenum cofactor (Moco), which acts as cofactor for the four enzymes listed (in humans - more enzymes use Mo in plants and bacteria). Moco consists of Mo bound to molybdopterin. Despite the name, the latter substance doesn't itself contain Mo, it is the substance which incorporates Mo.

Molybdopterin is synthesised de novo from GTP. What you say about moybdopterins being needed to recycle biopterin is not correct. The strucutres of these two compounds are related, both being of the pterin family, but otherwise there is no connection. Molybdopterin has nothing to do with BH4 recycling.

The cofactors for xanthine oxidase and aldehyde oxidase are iron-sulfur clusters, FAD and Moco.

The cofactors for sulfite oxidase are haem b and Moco.

The cofactor for mitochondrial amidoxine reducing component is Moco. The Uni-Prot entry for this protein notes one report of it being pyridoxal binding but whether this plays a cofactor role isn't really known. Actually not much seems to be known about this newly discovered Mo enzyme.

I don't follow the link you are making between Mo and vit A, either endogenous vit A production or with Zn and vit A and iron transport.

 

[Gondwanaland]

Many thanks for your observations, @alicec

Molybdopterin has nothing to do with BH4 recycling.

Since aldehyde reductase is involved in BH4 synthesis, I wonder if aldehyde oxidase activity would theoretically have some influence in aldehyde reductase function.

I don't follow the link you are making between Mo and vit A, either endogenous vit A production or with Zn and vit A and iron transport.

Xanthine oxidase also catalyzes the conversion of retinal to retinoic acid. (from the book Advanced Nutrition: Macronutrients, Micronutrients, and Metabolism)

http://lpi.oregonstate.edu/mic/minerals/zinc#nutrient-interactions
Zinc and vitamin A interact in several ways. Zinc is a component of retinol-binding protein, a protein necessary for transporting vitamin A in the blood. Zinc is also required for the enzyme that converts retinol (vitamin A) to retinal. This latter form of vitamin A is necessary for the synthesis of rhodopsin, a protein in the eye that absorbs light and thus is involved in dark adaptation. Zinc deficiency is associated with decreased release of vitamin A from the liver, which may contribute to symptoms of night blindness that are seen with zinc deficiency

http://lpi.oregonstate.edu/mic/vitamins/vitamin-A#red-blood-cell-production
Red blood cell production (erythropoiesis)
.... vitamin A supplementation in vitamin A deficient-individuals has been shown to increase hemoglobin concentrations. Additionally, vitamin A appears to facilitate the mobilization of iron from storage sites to the developing red blood cell for incorporation into hemoglobin, the oxygen carrier in red blood cells (27, 28).

Nutrient interactions
Zinc
Zinc deficiency is thought to interfere with vitamin A metabolism in several ways (29):
(1) zinc deficiency results in decreased synthesis of retinol-binding protein (RBP), which transports retinol through the circulation to peripheral tissues and protects the organism against potential toxicity of retinol;
(2) zinc deficiency results in decreased activity of the enzyme that releases retinol from its storage form, retinyl palmitate, in the liver;
and (3) zinc is required for the enzyme that converts retinol into retinal (30). The health consequences of zinc deficiency on vitamin A nutritional status in humans are yet to be defined (29).

Iron
Vitamin A deficiency often coexists with iron deficiency and may exacerbate iron deficiency anemia by altering iron metabolism (27). Vitamin A supplementation has beneficial effects on iron deficiency anemia and improves iron nutritional status among children and pregnant women (27, 28). The combination of supplemental vitamin A and iron seems to reduce anemia more effectively than either supplemental iron or vitamin A alone (31). Moreover, studies in rats have shown that iron deficiency alters plasma and liver levels of vitamin A (32, 33).

I think the severe anemia I get from taking small amounts of zinc (less than 10mg combined with a small dose of Cu) for 3-4 days can only be explained by the mechanisms described above, and if I find that taking Zn in combo with Mo prevents this problem I will report here.

 

[alicec]

Since aldehyde reductase is involved in BH4 synthesis,

The three enzymes involved in BH4 synthesis are GTP cyclohydrolase (GTPCH rate limiting), pyruvoyltetrahydropterin synthase (PTPS) and sepiapterin reductase (SR),

Dihydrofolate reductase (DHFR) and dihyropteridine reductase (DHPR) along with the poorly characterised sepiapterin synthase are involved in the salvage pathway.

Here is an illustration.

GTPCH and PTPS use zinc as cofactor. SR, DHPR and DHFR use NADP+/NADPH.

Xanthine oxidase also catalyzes the conversion of retinal to retinoic acid. (from the book Advanced Nutrition: Macronutrients, Micronutrients, and Metabolism)

Yes I had forgotten about this pathway.

The major pathway responsible for conversion of retinal to retinoic acid is via retinal dehydrogenase (3 versions) which uses NAD+/NADH as cofactor.

The xanthine oxidase pathway has been observed to occur in cytoplasm at least in in vitro studies but its significance is not understood and it appears to be a minor pathway.

I wasn't questioning the role of zinc and vitamin A, just the link to Mo.

This pathway could represent a link but KEGG pathways doesn't even show it - in other words it is of little importance.

 

[Gondwanaland]

@alicec Thanks again for explaining!

 

[Gondwanaland]

Here is a warning to people on HRT:

Stay away from Carcinine, because it speeds up hormone breakdown (all of them) and messes up with replacement therapy!

@IThinkImTurningJapanese Moderator please I would like to add this warning to the OP, could you please allow me to edit it?

 

[Gondwanaland]

This explains why I got so many white hairs from carcinine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349156/
Microb Cell. 2014 Jul 7; 1(7): 241–246.
Published online 2014 Jul 7. doi: 10.15698/mic2014.07.154
PMCID: PMC5349156
Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae
....
What functions of copper does excess histidine inhibit? Intracellular copper is distributed to distinct target proteins via specific cytosolic copper chaperons, such as Atx1, Ccs1, and Cox17. Atx1 assists in the transport of copper to the cell-surface iron uptake protein Fet3 through the function of Ccc2, which has copper-transporting ATPase activity, on the post-Golgi vesicle 41. Ccs1 delivers copper specifically to the superoxide dismutase Sod1, which scavenges reactive oxygen species in the intermembrane space of mitochondria 42,43. Another copper chaperon Cox17 transfers copper to the mitochondrial inner membrane proteins Cox11 and Sco1, both of which are essential for assembly of cytochrome c oxidase, which is the last enzyme in the respiratory electron transport chain 44. In this study, we tested whether histidine cytotoxicity might be mediated by defective mitochondrial functions due to reduced copper availability.
.....

In this study, we discovered the cytotoxicity of excess histidine in S. cerevisiae, which is tightly associated with the reduced availability of intracellular copper ions. Similarly, Pearce and Sherman 37 revealed that intracellular histidine synthesis is required for the detoxification of excess copper. Both studies commonly suggest that intracellular histidine has a novel and important role in copper homeostasis.

 

[Gondwanaland]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120975/
J Phys Chem B. 2014 Jul 31; 118(30): 8935–8944.
Published online 2014 Jul 11. doi: 10.1021/jp500767n

ESEEM Analysis of Multi-Histidine Cu(II)-Coordination in Model Complexes, Peptides, and Amyloid-β

We validate the use of ESEEM to predict the number of 14N nuclei coupled to a Cu(II) ion by the use of model complexes and two small peptides with well-known Cu(II) coordination. We apply this method to gain new insight into less explored aspects of Cu(II) coordination in amyloid-β (Aβ). Aβ has two coordination modes of Cu(II) at physiological pH. A controversy has existed regarding the number of histidine residues coordinated to the Cu(II) ion in component II, which is dominant at high pH (∼8.7) values. Importantly, with an excess amount of Zn(II) ions, as is the case in brain tissues affected by Alzheimer’s disease, component II becomes the dominant coordination mode, as Zn(II) selectively substitutes component I bound to Cu(II). We confirm that component II only contains single histidine coordination, using ESEEM and set of model complexes. The ESEEM experiments carried out on systematically 15N-labeled peptides reveal that, in component II, His 13 and His 14 are more favored as equatorial ligands compared to His 6. Revealing molecular level details of subcomponents in metal ion coordination is critical in understanding the role of metal ions in Alzheimer’s disease etiology.

Introduction
Among natural amino acids histidine is one of the strongest metal ion coordinators.1 Hence, histidine plays an important role in metal ion coordination in proteins and peptides. Histidine is a tridentate ligand, which provides ligands at the imidazole imido nitrogen, the amino nitrogen, and the carboxylate oxygen.2 The imidazole ring nitrogen of histidine residues often provides the primary coordination site for metal ions.2Copper is an essential metal ion for biological functions and is found in bound forms in metalloproteins and in low molecular weight complexes to avoid toxicity associated with free copper.2 Copper-containing proteins often have binding sites with irregular geometries containing one or more histidine ligands.
....

 

[Gondwanaland]

I wonder if the Carcinine molecule contains Molybdenum... I think it is the missing ingredient in Carnosine.

How are your feelings about it, @Asklipia ?

 

[Asklipia]

No idea!

 

[Gondwanaland]

No idea!

What do you think are your main food sources for Molybdenum?

 

[Gondwanaland]

In agreement with Dr. Lonsdale recommendation for potassium+magnesium in aspartate form, I see that lack of aspartate could be the cause of some problems I ran into with the carcinine:

https://examine.com/supplements/d-aspartic-acid/
D-Aspartate has been found to be a constituent of human cartilage,[4]enamel,[5] and can be accumulated in the brain[6] as well as being a constituent of red blood cell membranes.[7]

 

[Asklipia]

What do you think are your main food sources for Molybdenum?

Lentils or beans once a week as a main course.

 

[Gondwanaland]

This is why glycoxil increases the need for glycine:

http://openheart.bmj.com/content/1/1/e000103
With respect to diabetes, it is of interest that high intakes of glycine have the potential to oppose the formation of Amadori products, precursors to the advanced glycation endproducts (AGEs) that mediate diabetic complications.29,30 Indeed, supplementation of human diabetics with glycine—5 g, 3-4 times daily—is reported to decrease haemoglobin glycation.31,32

 

[Gondwanaland]

Interestingly there is a new Carnosine product now with added thiamine HCl and Benfotiamine.

 

[prioris]

Interestingly there is a new Carnosine product now with added thiamine HCl and Benfotiamine.

Life extensions carnosine contains Benfotiamine, thimiamine and Leotolin. They have had it for years.