Biosynthesis and Storage of FAs and TAG (Exam 2) Flashcards
Where does de novo synthesis of FAs occur?
LIVER
Some in the mammary gland during lactation
What is the source of carbons for FA synthesis? **
Acetyl-CoA fragments***
Coming from excess dietary carbohydrates and proteins
Where is the source of carbons for FA synthesis?
Acetyl-CoA fragments will be locked away in the mitochondria
Where does FA synthesis occur?
CYTOPLASM
(TRUE/FALSE)
The acetyl-CoA for FA synthesis must be taken from the mitochondria and transported into the cytoplasm.
TRUE**
Remember, it is INSIDE the MITO where we break down nutrients and that is where we make ATP.
How are the acetyl-CoA transported out of the mitochondria and into the cytoplasm?
- As the 1st step in the Krebs Cycle, Acetyl-CoA will complex with OAA via CITRATE SYNTHASE
- Citrate will then cross the mito membrane and enter the cytosol
- Citrate will be split via ATP CITRATE LYASE to form OAA and Acetyl-CoA
What is the enzyme that splits CITRATE in the cytoplasm?
CITRATE LYASE
What is the enzyme that complexes/combines OAA and Acetyl-CoA in the mitochondria?
CITRATE SYNTHASE
What is the first step in FA synthesis?
Acetyl-CoA is converted to Malonyl-CoA via ACETYL-COA CARBOXYLASE (ACC)
ACC (function)
Acetyl-CoA Carboxylase, a rate-limiting enzyme**
Catalyzes the first reaction in FA synthesis of Acetyl-CoA —-> Malonyl-CoA
How is ACC regulated?
Acetyl-CoA Carboxylase
1) Allosterically: ++ Citrate; – Palmitoyl-CoA (the final product of FA synthesis)
2) Covalent Modulation
What is palmitoyl-CoA?
It is the final step in FA synthesis; which negatively effects ACC allosterically
Explain covalent modulation of ACC.
1) ACTIVE = DEPHOS (High insulin/fed-state levels will activate PROTEIN PHOSPHATASE to dephos ACC, thereby activating it).
2) INACTIVE = PHOSPHORYLATED (High Glucagon, Epi/fasting-state, AMPK Kinase levels will activate AMPK to PHOS ACC, thereby inactivating it).
What is the main fragment that is used by FA Synthase Complex for FA synthesis?
Malonyl-CoA, will be added on in several steps, so each time it is elongated and reduced by NADPH.
The reducing will result in a 16 carbon saturated FA called PALMITATE
FA Synthase Complex
Has 2 domains:
1) Cysteine residue
2) Acyl-carrier protein
which will allow it elongated these malonyl-CoA fragments in FA synthesis
What is the reducing agent in FA synthesis?
NADPH
AMPK
AMP-activated protein kinase
Acts to phosphorylate ACC during fasting state, thereby inactivating it. It is allosterically regulated by ++ AMP levels.
What increases protein phosphatase enzyme in FA synthesis? What is the result?
Insulin will activate Protein Phosphatase enzyme which will DEPHOSPHORYLATE ACC, thereby activating it. So Acetyl-CoA will be converted to Malonyl-CoA.
Explain the long-term regulation of ACC.
Via gene expression level
1) Increased expression/activity with high carbohydrate, or low-fat diet
2) Decreased expression/activity of ACC with low-calorie, high-fat, or low carb diets.
(TRUE/FALSE)
The body can create saturated and unsaturated fats
TRUE
Through elongation and desaturation of palmitate, both occurring in the smooth endoplasmic reticulum
Explain the synthesis of TAG.
The FAs that are produced through FA Synthase Complex will be used to form TAG molecules within the LIVER.
The FAs must first be activated by FATTY ACETYL-COA SYNTHETASE first. This adds the CoA to each FA, allowing each FA w/ its CoA to attach to the glycerol-3-P molecule.
What happens once TAG is synthesized in the liver?
It will be exported as part of VLDL and will go to peripheral tissues to serve as an energy source via LPL (remember!). (The VLDL will then transition to IDL, then LDL).