lecture 13: choline

Question 1

CHTs

Answer 1

choline transporter
high affinity, saturable, sodium dependent, provide choline for acetylcholine synthesis in the presynaptic nerve terminal

Question 2

main form of choline in food and body

Answer 2

PtdCho, phospholipid with choline as polar head group, member of lecithin (amphipathic)

made by CDP-choline pathway or PEMT pathway

Question 3

low affinity sodium independent choline transporters

Answer 3

provide choline for phospholipid synthesis

Question 4

metabolism of choline

Answer 4

liver
1) phospholipid biosynthesis
2) conversion to methyl donor betaine

neurons: converted to acetylcholine

Question 5

PtdCho in liver can be used for…

Answer 5

membrane biogenesis
formation of bile
secretion in VLDL (VLDL transports it)

Question 6

PEMT pathway

Answer 6

makes choline from another precursor molecule

PE (non-choline substrate) > PtdCho via PEMT via 3 steps

methyl donor = AdoMet

Question 6

CDP-choline pathway

Answer 6

produces most of the PtdCho
impairment leads to apoptosis
begins with choline

1) free choline phosphorylated by CK
2) phosphocholine activated to CDP choline (rate limiting, catalyzed by CT)
3) CDP choline + DAG via CPT > PtdCho

Question 7

CT enzyme and regulation

Answer 7

activates phosphocholine to CDP choline

translocates to nuclear membrane in response to increased demand for PtdCho (PtdCho degredation, FAs, DAGs)

inactive soluble form and active membrane-bound form

activating lipids/PtdCho depletion increases membrane lateral packing stress > insertion of CT into membrane bilayer

Question 8

packing stress

Answer 8

activating lipids or PtdCho depletion increases membrane lateral stress > CT binding

Question 9

how is PtdCho made?

Answer 9

CDP-choline pathway or PEMT pathway

Question 10

PEMT pathway

Answer 10

sequential methylation of non-choline substrate PE > PtdCho
all steps catalyzed by PEMT
methyl donor = AdoMet

Question 11

methyl donors

Answer 11

methyl donors form AdoMet, which is formed from folate (methyl cycle) or betaine (oxidation of choline)

Question 12

Acetylcholine

Answer 12

neurotransmitter, controls output of many organs

Question 13

choline acetyltransferase (ChAT)

Answer 13

in the neuron, choline not used for PtdCho is used for acetylcholine synthesis

choline + acetyl-CoA > acetylcholine

Question 13

acetylcholine production

Answer 13

in neuron, choline not used for PtdCho is acetylated by ChAT to generate acetylcholine

acetylcholine packaged into synaptic vesicles

acetylcholine released into post-synaptic cleft

AChE: acetylcholine > acetate + choline (choline is recycled)

Question 14

where does free choline for acetylcholine synthesis come from?

Answer 14

low affinity transporter from blood transports free choline to neuron, high affinity transporter in neuron for recycling > formation of PtdCho or enter acetylcholine cycle
PtdCho can also be hydrolyzed by phospholipase D to free choline for acetylcholine biosynthesis

Question 14

choline deficiency

Answer 14

fatty liver and liver dysfunction are main clinical manifestations

PtdCho secreted in VLDL
Choline deficiency = inability to removed fat being produced in the liver

Question 15

why is it that fatty liver and liver dysfunction would be the main symptoms of choline deficiency?

Answer 15

VLDL PRODUCTION
transporter of lipids is not being excreted, it needs the PtdCho
can’t transport lipids in the liver without VLDL
inability to remove fat being produced in the liver

Question 16

what is free choline soluble in?

Answer 16

water soluble

Question 17

If CT translation is inhibited, how could choline still be involved in the production of PtdCho?

Answer 17

PEMT pathway

Choline can be transferred to mitochondria, oxidized to betaine, which is then released back to the cytosol to serve as the methyl group donor for PEMT pathway
donated to AdoMet, activated methyl group

Question 18

How might folate contribute to the production of PtdCho?

Answer 18

PEMT pathway
Folate provides the methyl groups necessary to Adomet → carry out sequential methylation reactions in PEMT → PtdCho

methyl donor is either folate or betaine