Steven Zeisel 1990 - Choline Deficiency Review

What are the 3 main uses of Choline?

1. Synthesize phospholipids that are crucial for membrane structure

2. Precursor to acetylcholine (ACh)

3. Methyl group donor

What makes a nutrient essential?

• Diminished tissue levels of the nutrient when removed from the diet

• Association with deterioration of organ function

What are the 3 main pieces of evidence that support choline is an essential nutrient?

1. Malnourished humans have low concentrations of choline

2. Human cells grown in vitro require choline

3. Humans on an IV TPA diet with little or no choline develop liver dysfunction

What is Sphingomyelin?

A sphingolipid and major component of cell membranes, especially in the myelin sheath.

What is Lecithin?

Lecithin is phosphatidylcholine and is commonly consumed in the human diet as an emulsifying agent and antioxidant.

What is the bioavailability of choline dependent upon?

efficiency of absorption in the small intestine

What are the 4 things that mammary cells metabolize choline into?

1. Betaine

2. Phosphocholine

3. Phosphatidylcholine

4. an unknown compound

What 2 things does the placenta use choline for?

Choline is delivered directly to the fetus and used to make acetylcholine for the fetus.

What are the 3 ways choline is metabolized and its metabolites?

• Acetylation (to acetylcholine)

• Phosphorylation (to phosphatidylcholine)

• Oxidation (to betaine)

What enzyme synthesizes choline into ACh? How?

Where is this enzyme located?

Choline acetyltransferase (ChAT) is the enzyme responsible for acetylation, the addition of an acetyl group (carbonyl group [C=O] + methyl group [CH3]) to choline, and is mainly located at the terminals of cholinergic neurons and in the placenta.

What is betaine and how is it metabolized?

Betaine is an important methyl donor and is metabolized via irreversible oxidation.

What is choline kinase and what does it do? What inhibits it?

Choline kinase phosphorylates choline by adding a phosphoryl (PO₃) group and is inhibited by adenosine.

Why do we think phosphatidylcholine is more important for cellular function than other forms of choline?

During choline deficiency, available choline is preferentially used for phosphatidylcholine synthesis, indicating its critical role in maintaining cellular function.

What enzyme is responsible for de novo biosynthesis of phosphatidylcholine occur?

Where is this enzyme found?

Why is it important?

The only source of choline other than diet is from the de novo biosynthesis of phosphatidylcholine catalyzed by PeMT, which is primarily localized within nerve endings