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Sunday, June 16, 2013

Dopamine Biosynthesis

Dopamine biosynthesis
The primary fault in Parkinson's Disease is that, whatever the cause, there is insufficient dopamine. Dopamine is formed in the dopaminergic neurons by the following pathway :
L-tyrosine >>> L-dopa >>> Dopamine
The first step is biosynthesised by the enzyme Tyrosine 3-Monooxygenase [1.14.16.2] (which is more commonly called by its former name tyrosine hydroxylase). The following is the complete reaction :
L-tyrosine + THFA + O2 + Fe2+ >>> L-dopa + DHFA + H2O + Fe2+
So for L-dopa formation, L-tyrosine, THFA (tetrahydrofolic acid), and ferrous iron are essential. The activity of this enzyme is often as low as 25% in Parkinson's Disease, and in severe cases can be as low as 10%. This indicates that one or more of the elements required for the formation of L-dopa are in insufficient quantities.
The second step in the biosynthesis of dopamine is biosynthesised by the enzyme Aromatic L-amino acid decarboxylase [4.1.1.28] (which is more commonly called by its former name dopa decarboxylase). The following is the complete reaction :
L-dopa + pyridoxal phosphate >>> dopamine + pyridoxal phosphate + CO2
So for dopamine biosynthesis from L-dopa, pyridoxal phosphate is essential. The activity of the enzyme rises and falls according to how much pyridoxal phosphate there is. The level of this enzyme in Parkinson's Disease can also be around 25% or even far less.

Coenzymes involved in Dopamine biosynthesis
Besides two enzymes being required for the formation of dopamine from L-tyrosine (L-tyrosine >>> L-dopa >>> Dopamine), three coenzymes are also required. Enzymes are substances that will enable a specific chemical reaction to take place in the body. Coenzymes are substances that assist enzymes. Some enzymes (including those involved in dopamine biosynthesis) will not function without coenzymes.
The three coenzymes involved in the formation of dopamine are : THFA (for L-tyrosine to L-dopa), Pyridoxal phosphate (for L-dopa to dopamine), and NADH (for the formation of THFA and Pyridoxal phosphate). They are made from vitamins via the following means :
Folic acid >>> Dihydrofolic acid >>> Tetrahydrofolic acid
Pyridoxine >>> Pyridoxal >>> Pyridoxal 5-Phosphate (this requires zinc as a cofactor)
Nicotinamide >>> NMN >>> NAD >>> NADH (or NADP) >>> NADPH

PART 3 : CELL DAMAGE

The first step in the formation of dopamine (L-tyrosine > L-dopa > dopamine) is the formation of L-dopa from L-tyrosine.

L-dopa is normally formed in the dopaminergic neurons by the following pathway :

L-tyrosine + THFA + O2 + Fe2+ >>> L-dopa + DHFA + H2O + Fe2+

There are two problems with this reaction not working. Primarily, if somebody does not form L-dopa, they will also lack the dopamine required to prevent Parkinson's Disease from occurring. No L-dopa formation ends up in somebody developing Parkinson's Disease.

However, there is also a cellular symptom of a failure to form L-dopa from L-tyrosine. This is the cell damage that occurs in Parkinson's Disease.

The primary natural means via which cell damage can occur in Parkinson's Disease is due to the reaction from L-tyrosine to L-dopa not taking place. The following is what should happen :

L-tyrosine + THFA + O2 + Fe2+ >>> L-dopa + DHFA + H2O + Fe2+

However, if for example, the THFA in the above reaction is lacking, the following can happen instead :

L-tyrosine + Fe2+ + O2 >>> L-tyrosine + Fe3+ + O-2 (superoxide anion)

As can be seen there is no L-dopa formed in the faulty reaction, and the superoxide anion is formed instead. The superoxide anion is one of the most highly destructive elements in cellsOXIDATIVE DAMAGE.   So you get a double problem : symptoms of Parkinson's Disease and cell damage.

The formation of L-dopa can also fail to take place if L-tyrosine is deficient.

So the simplest means of preventing cell damage from taking place is to ensure that you have those substances required for the formation of L-dopa, which are L-tyrosine, THFA (which is made from the vitamin folic acid using nicotinamide), and ferrous iron.

However, many people have instead tried to solve the problem of cell damage by other means, largely because they did not known the primary cause of the cell damage.

Vitamin C and Vitamin E have been used to try to help to prevent cell damage in Parkinson's Disease. This is because they are claimed to assist in two enzyme reactions in the brain that get rid of the superoxide anion once it has been formed :

Superoxide Dismutase [1.15.1.1] : 2O-2 + 2H+ >>> H2O2 + O2

Catalase [1.11.16] : H2O2 >>> H2O + 1/2 O2

Wednesday, May 22, 2013

Effects of Methylfolate in combination with other nutrients

I took methylfolate along with other nutrients for fine tuning the benefits of methylfolate.

L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + Pyridoxine HCl 10 mg/day (5 mg in morning and 5 mg in night) + methylcobalamin 500 microgram/day (500 microgram in morning)
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one capsule of Supradyn recharge in morning + methylcobalamin 500 microgram/day (500 microgram in morning) + Pyridoxine HCl 5 mg in night
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one capsule of Supradyn recharge in morning + methylcobalamin 500 microgram/day (250 microgram in morning and 250 microgram in night)
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one tablet of zincovit in morning + methylcobalamin 500 microgram/day (250 microgram in morning and 250 microgram in night) + one tablet of Calcium & Magnesium Plus (Elemental calcium 275.9 mg + elemental magnesium 125 mg + elemenatl manganese 1.5 mg + elemental zinc 300 microgram + Vitamin D3 100 IU)
Effects on anxiety
No anxiety
No anxiety
No anxiety
No anxiety
Effects on depression
No depressive feelings
No depressive feelings
No depressive feelings
No depressive feelings
Effects on stuttering and voice
Mild stuttering. Can make a fluent conversatioatin. No effect on loudness of voice
Less stuttering. Can make a fluent conversation. Good loudness of voice
Less stuttering. Can make a fluent conversation. Good loudness of voice
Less stuttering. Can make a somewhat fluent conversation. moderate loudness of voice
Effects on motivation
Slightly reduced Motivation
Reduced Motivation
Average motivation;. If methylcobalamin dose in increased, it produces less motivation and lethargic effects similar to that of fluoxetine. If methylfolate dose is increased, it creates increased motivation and restlessness.
Average motivation
Effects on concentration
Slightly reduced concentration throughout the day
Reduced concentration throughout the day
Slightly reduced concentration throughout the day
Average concentration
Effects on memory
Good
Good
Good

Effects on mental fog and clarity of thinking
Slightly reduced clarity of thinking
Reduced clarity of thinking
Nil to Slightly reduced clarity of thinking

Effects on telephonic conversation
Mild stuttering
Mild stuttering
Less stuttering and good speech

Effects on affection and social life
Neutral
Reduced affection towards family
Neutral

Effects on sleep
Not excessive sleepiness. Able to get up early in morning
Excessive sleepiness. Not able to get up early in morning, Uncontrollable sleeping after lunch in evening
Neutral

Effects on libido and sex
Neutral
Neutral
Neutral
seems to increase libido...gives good spontaneous erections...able to get strong erection after massaging for masturbation (this effect was better observed with medimix soap/chandrika soap). The soap is used for bathing only and not during the time of masturbation.
Effects on eye vision
Neutral
Neutral
Neutral

Effects on driving
Neutral
Neutral
Neutral

Effects on body temperature and sweating
Slightly increased sweating
Slightly increased sweating
Reduced body temperature and sweating

Other effects
Slight bad taste in mouth, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
Slight bad taste in mouth, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
No bad taste in mouth. No skin allergies. (If the tablets are taken after food)

Diet during these time
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables

Wednesday, May 8, 2013

Effects of methylfolate

I took 5 mg of folic acid per day (2.5 mg in morning and 2.5 in night). I felt more energetic and motivated. So, I have started experimenting with methylfolate.


L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one zincovit tablet  in morning + one Magcalzinc tablet in night (Elemental calcium 250 mg + Elemental magnesium 125 mg + elemental zinc 3 mg)
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one zincovit tablet  in morning
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night)
L-methylfolate 7.5 mg/day (3.25 mg in morning and 3.25 mg in night) + one capsule of fluoxetine in night
Effects on anxiety
No anxiety
No anxiety
No anxiety
No anxiety
Effects on depression
No depressive feelings
No depressive feelings
No depressive feelings
No depressive feelings
Effects on stuttering and voice
Moderate stuttering was there. Cannot make a fluent conversation. Reduced loudness of voice
Moderate stuttering was there. Cannot make a fluent conversation. Reduced loudness of voice
Moderate to severe stuttering was there. Cannot make a fluent conversation or presentation. Reduced loudness of voice
Much reduced stuttering. Can make a good presentation and conversation. Good loudness of voice
Effects on motivation
Good motivation
Good motivation
Good motivation
Reduced motivation and increased lethargy
Effects on concentration
Good concentration throughout the day
Good concentration throughout the day
Good concentration on tasks in morning. Low concentration in afternoons. Then, concentration increases after 7 pm.
Reduced concentration
Effects on memory
Good
Good
Good
Good
Effects on mental fog and clarity of thinking
Good
Good
Good
Reduced clarity of thinking
Effects on telephonic conversation
Moderate stuttering
Moderate stuttering
Moderate stuttering
Reduced stuttering
Effects on affection and social life
Longing for love from family members but no interest in social life
Longing for love from family members but no interest in social life
Longing for love from family members but no interest in social life
Reduced affection towards family but increased participation in social gatherings probably due to less stuttering
Effects on sleep
No excessive sleepiness. Able to get up early in morning
No excessive sleepiness. Able to get up early in morning
Not much of excessive sleepiness. But, heavy uncontrollable sleepy feeling after taking lunch.
Increased sleepiness. Cannot get up easily in morning.
Effects on libido and sex
Neutral
Neutral
Neutral
Neutral to less
Effects on eye vision
Neutral
Neutral
Neutral
Neutral
Effects on driving
Neutral
Neutral
Neutral
Neutral
Effects on body temperature and sweating
No ‘heated body’ feeling and no increased sweating
No ‘heated body’ feeling and no increased sweating
No ‘heated body’ feeling and no increased sweating
Increased sweating
Other effects
Moderate right hand wrist pain and forearm pain was there due to excessive computer mouse usage, bad taste in mouth, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
Mild right hand wrist pain and forearm pain was there due to excessive computer mouse usage, bad taste in mouth, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
No hand pain or wrist pain, bad taste in mouth, bad breath, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
Slight bad breath, mild skins rashes like an allergic reaction (red skin eruptions appear in line)
Diet during these time
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables
Oats porridge in morning and night; lunch – rice with 200 g of chicken or fish with 200 g vegetables