LECTURE 19 - FATTY ACID SYNTHESIS

Question 1

where does fatty acid biosynthesis happen?

Answer 1

in the cytosol
issue: you need to export acetyl CoA to the cytoplasm, from the mitochondria

Question 2

which metabolic circumstances require the synthesis of fatty acids?

Answer 2

to initiate cell division
after a glucose rich meal
after a fructose containing meal

Question 3

which intermediate of the citric acid cycle is the starting point of FA synthesis?

Answer 3

citrate
FA synthesis turns on when you fill up the glycogen pool

Question 4

how is acetyl CoA transported to the cytosol?

Answer 4

the citrate shuttle:
1. the CoA of acetyl CoA prevents it from crossing the mitochondria membrane
2. in the mitochondrium, acetyl CoA is converted to citrate by citrate synthase
3. citrate can cross the membrane without any issues
4. in the cytosol, citrate is converted to acetyl CoA and oxaloacetate by citrate lyase

Question 5

what fatty acid is used as a building block?

Answer 5

palmitate
16C
saturated

Question 6

what is the acetyl CoA carboxylase (ACC) reaction?

Answer 6

generates Malonyl CoA (3C) from Acetyl CoA (2C)
irreversible, rate limiting step of the synthesis of fatty acids
ATP breakdown provides the energy for the whole process to be exergonic

Question 7

what are the two activities of ACC?

Answer 7

biotin carboxylase activity (this one needs a biotin as a cofactor) and transcarboxylase activity

Question 8

what is the function of Malonyl CoA?

Answer 8

inhibits CPT1
turns off FA breakdown

Question 9

what is ACP?

Answer 9

acyl carrier protein

Question 10

what is the malonyl/acetyl CoA transacylase reaction?

Answer 10

couples acetyl CoA and malonyl CoA with ACP
this keeps acetyl and malonyl activated, prevents leakage to other compartments
makes Malonyl ACP and acetyl KS

Question 11

what is the enzyme that synthesizes fatty acids?

Answer 11

fatty acid synthase (FAS)

Question 12

how does synthesis of palmitate happen?

Answer 12

Question 13

what is the structure of FAS?

Answer 13

very large protein
many domains
all catalytic activities are present on one monomer
two domains make thioester bonds (KS and ACP) and ACP is the main one
the substrates are passed on from active site to active site
2 homodimers organised in an upside down orientation
domains interact with each other
VERY FAST (less than a second from Acetyl CoA to palmitate)

Question 14

what is invested/lost in one cycle of synthesis of palmitate?

Answer 14

2 NADPH used (from the PPP)
one CO2

Question 15

what is the stoichiometry for the malonyl CoA reaction?

Answer 15

Question 16

what is the overall stoichiometry for the palmitate synthesis?

Answer 16

Question 17

what are the three states of acetyl CoA carboxylase (ACC)?

Answer 17

active (dimerised)
phosphorylated (monomeric, low activity)
phosphorylated (inactive)

Question 18

how is ACC regulated?

Answer 18

allosteric regulation:
activated by citrate, which promotes polymerisation
inhibited by fatty acids

hormonal regulation:
insulin stimulates glucose uptake and pyruvate dehydrogenase to make more acetyl CoA (slightly activates it)
glucagon and epinephrine inhibit ACC by PKA mediated phosphorylation

Question 19

how does elongation of FAs happen? (if you need something longer than palmitate)

Answer 19

happens in the mitochondria and the cytoplasmic face of the ER
Begins with activation of palmitate by the addition of a CoA group
addition of acetyl CoA to palmitate, reverse of oxidation
one NADH and one NADPH is used for each cycle

Question 20

how does desaturation happen?

Answer 20

4 terminal desaturases in mammals
at positions delta 9, 6, 5, and 4

Question 21

what are linoleic acid and linolenic acid and how are they obtained?

Answer 21

essential fatty acids that have to be acquired through plants for mammals because mammals do not have desaturases beyond delta 9

Question 22

what is the order of elongation/desaturation?

Answer 22

elongation happens before desaturation

Question 23

what are prostaglandins and leukotrienes?

Answer 23

important mediators of inflammation (pain, fever)

Question 24

what are inhibitors of prostaglandins and leukotrienes?

Answer 24

NSAID (non steroidal anti inflammatory drugs) inhibit them
examples: aspirin, ibuprofen etc