Fatty Acid Synthesis

Question 0

How is fat synthesis from glucose regulated?

Answer 0

1) supply of substrate ie high glucose availability
2) low level of production- NEFACoA inhibit (high car diet inhibit synthesis de novo?)
3) endocrine regulation of enzyme activity by covalent modulation
-insulin positive;/ glucagon, adrenalin, growth hormone, ACTH: ALL negative
-regulation at PFK2 and therefore PFK1
-regulation at acetyleCoA carboxylase-activated by insulin (dephosphorylates)
Plus allosteric activation by citrate, inhibited by NEFA CoA
4) endocrine regulation of enzyme expression- dominated by insulin
-increased synthesis of NADP malate dehydrogenase, ATP citrate lyase, acetyl CoA carboxylase and fatty acid synthase.
REMEMBER: Regulation at acetylCoA carboxylase is the most important

Question 1

What are the 4 major steps of fat synthesis from glucose?

Answer 1

Fat synthesis from glucose➡ idea is to string 16 carbons together to form palmitic acid. The carbon comes from acetylCoA abs tge hydrogen electrons from NADPH.

1) formation of AcetyleCoA in the cytoplasm (glycolysis/ citrate cleavage pathway)
2) AcetylCoA carboxylase- the key rate limiting and regulatory steps
3) fatty acid synthetase
4) the provision of reducing

Question 2

Fat synthesis from acetate

Answer 2

Ruminants have a fermentation vat at the beginning if the digestive tract and this greatly modifies the end products if absorption. On roughage diets they consume little starch and high levels of cellulose.
The dietary carbs is extensively fermented by the rumen microorganisms to yield acetate, proprionate and butyrate. Proprionate is used for gluconeogenesis (the ruminants major source of glucose) whilst acetate supply in excess I’d oxidative demand is used for lipogenesis- this preserves glucose.

• acetate as a source of carbon
• acetate as a source of NADPH2 via cytosolic NADP isocitrate dehydrogenase

Question 3

Regulation of fat synthesis from acetate

Answer 3

The regulation is more simple here- it involves acetate and NEFACOA as above ans after thus the regulation if almost entirely at acetylCoA carboxylase

Question 4

The balance between the liver and adipose tissue

Answer 4

The site of lipogenesis vary between species. In some species lipogenesis predominates in the adipose tissue while in other the liver is the site of lipogenesis, with the resulting NEFA being released at triacylglycerol packed into VLDLs lipoprotein- the VLDLs can then be utilised by adipose tissue. Some species are a mixture of both