|Lecture Notes: 2 February||
The reactions of fatty acid synthesis all take place in the cytosol, but acetyl-CoA is made in the mitochondria and can't cross the inner membrane. The Pyruvate-Malate Cycle (Citrate-Pyruvate Cycle) [overhead] (packet) is used to take acetyl- groups to the cytosol while simultaneously providing a source of NADPH from NADH, and thus coupling fatty acid synthesis to Glycolysis. Note that the acetyl-CoA is first joined to oxaloacetate to make citrate which is readily transported out of the mitochondria using a co-transporter. The citrate is then cleaved to acetyl-CoA and oxaloacetate, a process requiring ATP to make it favorable (recall the condensation was spontaneous). Acetyl-CoA for fatty acid synthesis is now available in the cytosol, but oxaloacetate must be regenerated for the mitosol.
The cytosolic oxaloacetate is now dehydrogenated to give malate and NAD+. Malate is next oxidized by Malic enzyme to give pyruvate in a reaction which also provides NADPH for use in biosynthesis. (Note that NADH generated in Glycolysis is "converted" to NADPH for F.A. synthesis in these two reactions, while simultaneously regenerating the NAD+ needed to continue Glycolysis!) The pyruvate can now cross into the mitosol to be used in regenerating oxaloacetate.
Now we have all of the pieces of fatty acid biosynthesis starting from glucose. Let's look at the integration of the various pathways involved: Glycolysis, hexose monophosphate shunt, Pyruvate-malate shuttle, and Fatty acid biosynthesis. Notice the provision of reducing equivalents, redox balance and provision of required cytosolic ATP's as well as carbon source.
ELONGATION OF FATTY ACIDS
Plants and animals differ in where double bonds are introduced into fatty acids.
Plants put in 9 (a 9-10 double bond) and then can put in double bonds at three carbon intervals towards the tail (12, 15). They can also add 6, but not common.
Animals also start with 9, then can add at three carbon intervals toward carboxy end (6 and 3). Animals cannot add towards the tail. Therefore animals cannot make linoleoyl-CoA (9, 12; C18) but can make oleoyl-CoA (9; C18). Animals must therefore take in plant products (either directly as herbivores, or indirectly by eating herbivores) to acquire essential unsaturated fatty acids such as linoleic and arachadonic acids.
Both plants and animals use mixed function oxidases (simultaneously oxidize two substrates): Acyl-CoA desaturases localized on the ER. Similar mixed function oxidases are also used to modify structural components of cells, hormones etc. We will use the acyl-CoA desaturase as an example for this group of enzymes. In the acyl-CoA desaturase reaction molecular oxygen is used to oxidize both a fatty acid and NADH, each providing two of the the four electrons needed by the oxygen:
Last modified 31 January 2009