Make No Mistakes About MTHFR and Brain Function

Keep Methylation Central

To understand attention, attention based learning, motivation, pleasure,
and the other functions of the neurotransmitter dopamine,
you have to know something about D4 dopamine receptors.
And critical to the function of dopamine receptors
is the MTHFR C677T gene and enzyme.


The function of the D4 dopamine receptor
depends upon the cell membrane in which they are embedded.

The membrane surrounding your cell, the plasma or cell membrane,
is represented above by a three dimensional fluid mosaic.
It is composed of a bi-lipid layer,
a double layer of lipid or fat, which has a head at one end.
The lipid is actually phospholipid.

Nerve cells also have a phospholipid cell membrane.
In this depiction, the head is represented
by the red, green, purple and lime green rounded structures.
Anyone who has listened to the Tuesday night calls
has heard me talk about phospholipids at length.

Phosphatidyl serine complex is the important shortcut support
that almost everybody starts out on.
It is a complex of the same phospholipids in the nerve cell wall.

Receptor sites are positioned in the cell membrane.
They are represented by pink lobed molecules
with antenna-like structures projecting out of them.
The antenna-like structures grab the appropriate molecule
for the type of receptor involved and transport it into the cell.

The cell membrane must be fluid. It can’t be rigid.
If it is too rigid,
the molecules in the membrane can’t move or function properly.
They need to be able to move in order to signal appropriately.

Some receptors function by totally inverting into the cell.
They invert and pull the substance into the cell by doing so.
You cannot have a stiff, inflexible cell membrane and do this effectively.
That is what is wrong with trans fats: they are too stiff.

The receptor I am focusing on today is the D4 dopamine receptor.
Dopamine is the neurotransmitter responsible
for attention, motivation, pleasure and reward motivated behavior.
It is an extraordinarily important neurotransmitter
because it is the predominant neurotransmitter in your pre-frontal cortex.

Cognitive behavior is processed in your pre-frontal cortex.
It is where your executive function resides.
It’s the brain power you use to cross the street,
the mental apparatus that you need to make decisions.
It’s the seat of your personality,
the home of all the characteristics that make you you.

The D4 dopamine receptor is responsible for attention
and attention initiated learning.
It operates by inverting into the cell.
A very fluid cell membrane is necessary to do this.
Without this fluidity, you may get a diagnosis
of Attention Deficit Disorder or Attention Deficit Hyperactivity Disorder.

Dopamine activation of the D4 receptor
initiates a cycle of phospholipid methylation.
There is actually a methionine cycle which produces methyl groups
attached to this dopamine receptor.

4-14 methyl group

Depicted above is the bi-lipid layer of the phospholipid cell membrane.
The oval structure is a representation of a receptor site
which is made of protein.

On the left side, there is no phospholipid methylation.
There are no methyl groups
between the heads of the molecules in the membrane.

When there is space made by the methyl groups
between the phospholipid heads,
there is more room for the receptors to be able to move and function.
It is a more fluid membrane.
The protein receptor will be able to move around better
and will be able to signal and react with other proteins more easily.

Inadequate methylation negatively impacts your ability to attend and learn.
The dopamine receptor needs to be able to reconfigure itself.
It needs to be able to invert itself into the cell
and then come back out again.
It is not able to do that if the membrane is inflexible.

Phospholipid methylation, the addition of a methyl group to phospholipids,
reduces the packing density of the membrane
and enhances the activity of embedded, integral membrane proteins
like the D4 receptor.

The D4 receptor has a methylation cycle associated with it.
The activity of this methylation cycle is affected
by the availability of 5 methyl tetrahydrofolate (5 MTHF).
When the level of 5 MTHF is decreased, it becomes a limiting factor.
The receptors wait for a new methyl group to start the activation.
Receptors sitting around waiting for methyl groups
greatly reduces the impact of any dopamine present.
Even very high amounts of dopamine that may be present
will not activate the receptor if there is too little 5 MTHF.

And what determines 5 MTHF availability?
The function of MTHFR gene and the enzyme for which it encodes.
These are critical for an adequate supply of 5 MTHF.
MTHFR 3 is even a more profound genetic down regulation
of enzyme activity than MTHFR C677T.
So proper function of MTHFR or appropriate supplementation
of 5 MTHF are necessary for the function of dopamine
which is critical for good brain function.

My Tuesday night call is your chance to learn what you need to know
to get this important area of your life and biochemistry under control.
I take your questions on many topics,
among them the impact of your personal genetics on your biochemistry.
I discuss how to balance your biochemistry with nutritional supplements
that bypass problem genetics.

It is up to YOU to learn about treating psychiatric
and other chronic illness successfully.

You need to know about
the role of optimizing both methyl group production
and your capacity for methylation.

This is your opportunity.

My Tuesday evening calls are ongoing. They happen every week.
There is no charge to come on this call.
It is a free forum where you can ask your questions.
It’s a great way to clear up confusion,
overcome the obstacles you may be having,
and get on the path to wellness.

The time: Tuesday at 5:00 PM Pacific Time
(8:00 PM Eastern, 7:00 PM Central, 6:00 PM Mountain)
The number to call in the US: (559) 726-1300
The access code: 986935#

International access numbers are available.
Join us to inform yourself so that you can be proactive about your health!

So excellent!
I literally learn something on every single call
and I get clarification on things that have been lingering in my mind…

You are giving people a huge gift by empowering them…
It’s about helping the patient become their own healer
by taking them to a higher level of consciousness…

Thank you so much Dr. Mullan.
Thank you so, so much for everything you do.

Wow! I have to tell you, this was such an uplifting call.
It’s so nice to hear good news especially about a child.
Anxiety, OCD and a host of other mental/psychiatric symptoms
have been a huge hurdle for me.
So to hear this story of all those awful symptoms
totally going away is such a bright light for me!!!!


Nancy Mullan MD
Author, lecturer, clinician
Dr. Nancy Mullan is best known for her natural treatment of chronic illness,
including Autism Spectrum Disorders, Lyme and MTHFR+.

2829 Burbank Blvd., Suite 202, Burbank, CA 91505
T: (818) 954-9267 – F: (818) 954-0620


About Nancy Mullan, MD

Some people call Dr. Nancy Mullan the MTHFR genetic medicine expert. Dr. Mullan works with people who are struggling with chronic disease or other significant illness, who are willing to use diet and genetics-based nutritional supplementation, and who want to increase wellbeing and energy, enhance immunity, lift mood, fine-tune genetic function, and get their lives back. Dr. Mullan has studied at a number of exceptional institutions: the University of Pennsylvania, Tufts University School of Medicine, and the University of Chicago Hospitals and Clinics. She excels at integrating the results of biochemical and genetic testing into sustained clinical improvement for you. She has succeeded with patients who confounded the specialists at Massachusetts General Hospital, the Mayo Clinic, the Cleveland Clinic, Stanford, and many well-known integrative medical doctors. When recommending her, her patients say, “This is the woman you need to talk to. She really knows how to handle tough clinical problems.” Dr. Mullan's specialty areas are MTHFR+, methylation genetics, and genetics-based nutritional supplementation. Within this context, she most often works with Chronic Fatigue Syndrome, Lyme Disease, Psychiatric Disorders, Autism Spectrum Disorders, Women’s Health Issues, Thyroid Disorder, Gastrointestinal Disorder, and Heavy Metal Toxicity.
This entry was posted in Uncategorized. Bookmark the permalink.

Leave a Reply

Please log in using one of these methods to post your comment: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s