Triacylglycerol synthesis

Question 1

Kennedy pathway

Answer 1

Starting material is Glycerol-3-phosphate. GPAT adds first fatty acid from FA CoA. AGPAT uses FA CoA to add the second FA. PAP then removes the phosphate group and DGAT adds the last FA CoA to make triacylglycerol.
4 rxns
GPAT–>AGPAT–>PAP–>DGAT

Question 2

Where are the substrates for TG synthesis coming from

Answer 2

Derived from glucose (glycolysis)

Question 3

T/F fatty acids used to synthesize TG have to be bound to CoA to be activated

Answer 3

true

Question 4

Which GPAT are in the mitochondria and which are in endoplasmic reticulum

Answer 4

GPAT1 and GPAT2 are in mitochondria
GPAT3/10 and GPAT4/6 in endoplasmic reticulum

Question 5

Which GPAT is important for TG production

Answer 5

GPAT 3 and 4 because it they are found in adipose tissue

Question 6

What do GPAT3 and 4 do

Answer 6

Produce 1-acylglycero-3-phosphate for TG biosynthesis. GPAT4 can compensate for GPAT3

Question 7

How many AGPATs are there and which is the most used

Answer 7

AGPAT 2

Question 8

what is Berardinelli-Seip Syndrom

Answer 8

human without AGPAT2
Lipodystrophic disease
inability to synthesize TG
No AGPAT activity even though AGPAT2 is the only one impaired
TG accumulates in the liver resulting in liver damage
lack adipose tissue
Free fatty acids get redirected to the liver

Question 9

How can adipose tissue be visualized

Answer 9

MRI

Question 10

What does Phosphatidate phosphohydrolase do

Answer 10

catalyzes phosphatidate to 1,2-diacylglycerol
removes phosphate group

Question 11

What happens to DG and TG in yeast without Pah1P

Answer 11

DG and TG levels decrease

Question 12

What are fld mice

Answer 12

fatty liver dystrophy. Has a spontaneous mutation that results in almost no TG. Insulin resistant. Hypertriglyceridemia
mutation in the lipin gene

Question 13

is there a human version of Pah1

Answer 13

lipin

Question 14

what is the function of Lipin

Answer 14

transcriptional coactivator
Works with other transcription factors to activate genes needed for FA oxidation
is also an enzyme and accounts for all PAP activity in adipose tissue

Question 15

Where is lipin1,2,3 expressed

Answer 15

Lipin1 mainly in adipose
2 and 3 in liver not in adipose

Question 16

What does DGAT do

Answer 16

adds the third and final FA to 1,2-diacylglycerol

Question 17

What is ACAT 1 and 2

Answer 17

catalyzed cholesterol and FA-CoA to cholesterol ester

Question 18

how was DGAT discovered

Answer 18

Initially called ACAT3 because it shared similarities with ACAT 1 and 2. It didnt have the same activity as the two others. After trying to find the substrate for the enzyme it was found it acts on diacylglycerol. it was found it adds the final FA to diacylglycerol and was renamed to DGAT

Question 19

What happened to DGAT1 knockout mice

Answer 19

Still had TG and adipose but had decreased fat mass and TG. DGAT2 compensates, no fatty liver.
Found that they were resistant to diet-induced obesity when fed fatty diet
Same weight and TG when fed low fat

Question 20

How do DGAT1 ko mice synthesize TG

Answer 20

there is another DGAT enzyme that is inhibited by MG2+
called DGAT2

Question 21

What is DGAT2 inhibited by

Answer 21

Mg2+

Question 22

What happened to DGAT2 KO mice

Answer 22

Dies hours after birth because DGAT2 is essential for life. Skin abnormalities.
DGAT2 is involved in lipid metabolism in the skin

Question 23

Why do DGAT2 ko mice die

Answer 23

DGAT2 is involved in lipid metabolism in the skin and helps prevent water loss. Leads to rapid dehydration and death due to defective skin permeability barrier.

Question 24

What happens in DGAT1 and 2 KO mouse only in adipose tissue

Answer 24

Mouse is viable, still has TG in adipose tissue meaning there’s another enzyme TMEM68

Question 25

What is the PAP in yeast

Answer 25

PAH1
from the Pah1P gene

Question 26

What is the disease called which lacks AGPAT2

Answer 26

Berardinelli-Seip syndrome