Biosynthesis of FAs Flashcards
Effect of unsaturation on melting point
Decrease the melting temperature of fatty acid
What effect does the cis double bond in an unsaturated FA have on cell membranes?
Increases fluidity of the cell membrane, making it more flexible
How to name FA
- Use the carbon numbers starting with carboxyl group as C1 (including carboxyl group) so 20:4(5,8,11,14) = 20 carbons, with 4 double bonds and the locations are in parentheses
- 2nd carbon is alpha and keep going through Greek alphabet. Methyl group is always omega, so Omega-6 = 6 carbons back from the final C.
Lineoleic acid
- Precursor of arachadonic acid, which is the substrate for prostaglandin synthesis
- Also the precursor of other omega-3 FA, and is important for growth and development
Important functions of FA
- Major hydrophobic components of all cell membranes
- Major storage form of metabolic energy, TAGs are main caloric reserve
- Essential precursors for the eicosanoids
Major sources of FA
- Biosynthesis from small molecule intermediates derived from metabolic breakdown of sugars, AA, and fats
- Diet essential FA (Linoleic and linoleic acid)
When are FA synthesized?
When dietary calories are in excess and you get excess Acetyl-CoA
How does FA synthesis lead to stimulation of gluconeogenesis?
- High ATP inhibits TCA cycle, which then allows citrate to accumulate
- Citrate is then passed on for further FA synthesis as well as regeneration of OAA for gluconeogenesis
What is the RLS for FA biosynthesis?
Formation of malonyl-CoA
Can also inhibit the enzyme with LCFAs
FAS
- 7 different enzyme activities
- Acyl Carrier Protein (ACP)
- Performs all the steps to convert malonyl CoA to a FA
Malonyl CoA to FA
- Regulated by FAS
- Synthesized 2 carbons at a time (4-step repeating cycle)
- Repeat cycle 7 times to produce palmitic acid (16:0), which can then undergo separate elongation and/or desaturation to yield other FA molecules
Synthesis of palmitate by FAS
- Condensation to form acetoacyl ACP
- Reduction of the keto group to an alcohol
- Dehydration to introduce a double bond
- Reduction of the double bond
(numbering is from his diagram in PPT)
Elongation and desaturation
- Occur in the ER or mitochondria
- Performed by FA elongases
Diet and metabolic conditions for FA synthesis
- High carb = high pyruvate and acetyl CoA in mitchondria –> stimulate FA synthesis
- High fat/low carb diet = low pyruvate flux –> reduced FA synthesis
- Hormonal environment = high insulin favors lipogenesis and decreased FA biosynth,
Short-term regulation of FA biosynthesis
Citrate:
- Availability of cytosolic citrate determines amount available for synthesis
- Citrate activates ACA carboxylase and increase Vmax
Palmitoyl CoA
- Inhibits ACA carboxylase
- Cytosolic levels are high in starvation or high fat diets
Insulin and glucagon:
- Insulin promotes FA synthesis by dephospho ACA carboxylase
- Increases intracellular cAMP which leads to phospho of ACA carboxylase