Lipid Synthesis Flashcards
What are triglycerols?
Main storage form of FA in the body
Where/when are FA synthesized?
From: acetyl CoA in liver cells
When: whenever ingested calories exceed the requirement for energy
What happens to isocitrate dehydrogenase in conditions of excess energy?
Inhibited by high NADH/NAD+ ratio, drives citrate toward fatty acid synthesis
What are the two functions of pyruvate/malate cycle in lipogenesis?
- transport acetyl CoA from mitochondria to cytosol
2. Malic enzyme generates NADPH to power fatty acid synthesis
What is the first key regulatory step in FA synth?
Cytoplasmic Acetyl co A > malonyl CoA by addition of Co2
ACC–ACETYL COA CARBOXYLASE (biotin is cofactor)
How is the fist key regulatory step regulated in the forward direction?
FORWARD–Occurs in fed state when we want to store fat
- Citrate–allosterically activates
- Insulin– increases transcription
- Xylulose 5P– increases transcription (interm of pentose phos pathway, activates transcription at acetyl coA promoter)
- Insulin- stimulates dephosphorylation of activating enzyme
How is the first key regulatory step inhibited?
- Palmitoyl coA allosterically inhibits
- Phosphorylation by AMP-PK inhibits
- Glucagon–> cAMP –> PKA –> inhibitory phosphorylation
Why is malonyl CoA also a key regulatory step?
The body/hepatocytes dono’t want to synthesize fatty acids at same time that it’s oxidizing acids. Inhibits carnitine palmitooyl transferase 1, preventing B oxidation of newly synthesized FA
What is the reaction sequence in beta oxidation of fatty acids?
Oxidation
Hydration
Oxidation
Bond cleavage
In mitochondria, multiple proteins each step
What is the reaction sequence in FA synthesis?
Bond formation
Reduction
Dehydration
REduction
Cytosol, 1 enzyme compartment carries out all 4 steps
What is the Fatty acid synthase?
A large enzyme with multiple activites.
Has 2 important S atoms.
1. from a phophopantetheinyl (V5) group covalently linked to a serine residue on acyl carrier protein subunit of FAS. Provides active S.
2. From a cysteine side chain on another protein subunit of FAS.
What are the activites of FAS?
- Bond formation
-two CC units are added to S1, then transfered to acyl chain on cystein S
-first two carbon units from acetyl co a, second from malonyl CoA - Reduction– keto group is reduced to alcohol. Nadph oxidation powers rxn
- Dehydration rxn removes water and introduces a CC double bond
- Reduction–CC double bond is reduced, oxidation of NADPH +H powers reaction
THIS FORMS A 4 C FATTY ACID CHAIN.
4 C fatty acid is transfereed from PPP S to the cysteine S, new malonyl CoA can bind to the PPP S and chain elongation continues until acyl chain is 16 C long.
How does fatty acid chain elongation occur?
Palmitoyl CoA is elongated 2 C at a time in the ER.
Malonyl CoA donates 2 C, then added keto group undergoes R,D,R to produce saturated FA chain.
When can the body unsaturate CC bonds?
When the are at least 9 c away from omega end
What omega fatty acids are essential dietary precursors for synthesizing epicosonoids?
Omega 3, Omega 6
From plant and fish oils
Need dietary source with unsaturations further on