Triacylglycerol synthesis Flashcards
Kennedy pathway
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
Where are the substrates for TG synthesis coming from
Derived from glucose (glycolysis)
T/F fatty acids used to synthesize TG have to be bound to CoA to be activated
true
Which GPAT are in the mitochondria and which are in endoplasmic reticulum
GPAT1 and GPAT2 are in mitochondria
GPAT3/10 and GPAT4/6 in endoplasmic reticulum
Which GPAT is important for TG production
GPAT 3 and 4 because it they are found in adipose tissue
What do GPAT3 and 4 do
Produce 1-acylglycero-3-phosphate for TG biosynthesis. GPAT4 can compensate for GPAT3
How many AGPATs are there and which is the most used
AGPAT 2
what is Berardinelli-Seip Syndrom
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
How can adipose tissue be visualized
MRI
What does Phosphatidate phosphohydrolase do
catalyzes phosphatidate to 1,2-diacylglycerol
removes phosphate group
What happens to DG and TG in yeast without Pah1P
DG and TG levels decrease
What are fld mice
fatty liver dystrophy. Has a spontaneous mutation that results in almost no TG. Insulin resistant. Hypertriglyceridemia
mutation in the lipin gene
is there a human version of Pah1
lipin
what is the function of Lipin
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
Where is lipin1,2,3 expressed
Lipin1 mainly in adipose
2 and 3 in liver not in adipose
What does DGAT do
adds the third and final FA to 1,2-diacylglycerol
What is ACAT 1 and 2
catalyzed cholesterol and FA-CoA to cholesterol ester
how was DGAT discovered
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
What happened to DGAT1 knockout mice
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
How do DGAT1 ko mice synthesize TG
there is another DGAT enzyme that is inhibited by MG2+
called DGAT2
What is DGAT2 inhibited by
Mg2+
What happened to DGAT2 KO mice
Dies hours after birth because DGAT2 is essential for life. Skin abnormalities.
DGAT2 is involved in lipid metabolism in the skin
Why do DGAT2 ko mice die
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.
What happens in DGAT1 and 2 KO mouse only in adipose tissue
Mouse is viable, still has TG in adipose tissue meaning there’s another enzyme TMEM68
What is the PAP in yeast
PAH1
from the Pah1P gene
What is the disease called which lacks AGPAT2
Berardinelli-Seip syndrome
