January 22, 2013

Memory Loss, Methylation and Membranes.

Homocysteine and Methylation:

Our bodies try to keep homocysteine below certain limits; raised levels have harmful effects.

For example, a high homocysteine makes it difficult for your body to carry out an important process called 'methylation'.

This involves moving methyl groups or 'single carbon units' around; you can think of them as small Lego units perhaps.  Despite their size, moving these small units around is a vitally important process.

Methylation, Choline, Memory and Learning:

Methylation is important in making a nerve cell messenger called acetylcholine. Acetylcholine plays a key role in memory and learning.  Low levels contribute to memory problems in Alzheimer's Disease.

Acetylcholine is made from choline delivered to nerve cells; it is so important it is also recycled.  Nerve cells store choline in their cell membranes in a special phospholipid form called phosphatidyl-choline (PC).  Three methylation reactions are needed to make PC from phosphatidyl-ethanolamine (PE).  So, choline stores fall when methylation is impaired by high homocysteine.

Phospholipid Flip-Flops:

Phospholipid methylation also affects signal transmission across nerve cell membranes.  Membrane phospholipids are asymmetrically distributed.  PE largely faces inside the nerve cell; PC faces outside.  The methylating enzymes (PEMT 1 and 2) are also asymmetrical. Phospholipid methylation begins on the inner side of the membrane; methylated phospholipids move from inside to outside in a ‘phospholipid flip-flop.’  

This rearrangement makes the cell membrane much more fluid (Science 1980;209:1082-90).  The process is coupled to calcium flow into the nerve cell, and the release of other chemical messengers inside the cell.

Methylation and other neurotransmitters:

Methylation is also important for other nerve cell messengers called catecholamines.  Catecholamines such as noradrenalin, serotonin and dopamine are broken down by two enzymes - monoamine oxidase and catechol-O- methyl transferase (COMT).  The COMT enzyme methylates one of the catechol hydroxy groups to a methoxy derivative.  This deactivates catecholamines and so alters their neurotransmitter functions.

In summary, a high homocysteine means impaired methylation, and this influences signalling between nerve cells in the brain.

In our next Blog Update we will look at other ways in which a high homocysteine is bad for the brain.

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