Lecture 24: Lipid Metabolism II Flashcards
Describe the basic overview general flyby starter of lipid synthesis
- Occurs primarily in the liver
- Also in brain, kidneys, and adipose tissue
- Components located in cytoplasm
– Enzymes
– Acyl carrier proteins
– Co-factors
– Reducing power
– Energy (ATP)
What are the major steps in the synthesis of fatty acids
- Formation of Acetyl CoA
- Conversion of Acetyl CoA to Malonyl CoA
- Elongation (addition of carbons)
- Desaturation (introduction of double bonds)
See slide 7-8
Describe the conversion of acetyl CoA to Malonyl CoA
- Rate limiting step in fatty acid biosynthesis
- Catalyzed by Acetyl CoA carboxylase (ACC)
- Acetyl CoA is converted to malonyl CoA by carboxylation
- ACC adds a CO2 to acetyl CoA
- See Slide 9
Describe the regulation of ACC
- Allosteric regulation
- Citrate (+)
- Long chain fatty acids (-)
- Phosphorylation (-)/Dephosphorylation (+)
- Insulin (+)
- Epinephrine (-)
- Glucagon (-)
- Induction/repression
- Gene expression up-regulated by high carbohydrate/low fat diet
- Gene expression down-regulated by high fat/low carbohydrate diet
Describe the elongation of fatty acids
- Two carbon units from malonyl CoA are sequentially added to the growing fatty acyl chain to form palmitate (16:0).
- The reactions of fatty acid synthesis occur on the Fatty Acid Synthase Complex.
Describe fatty acid synthase
- Large multi-enzyme complex.
- Composed of 2 identical dimers (260 kDa each).
- Each has 7 catalytic activities and an acyl carrier protein (ACP).
- ACP segment has a phosphopantetheine (PP) residue.
- Two dimers arranged in head to tail conformation - PP of one is aligned with a cysteinyl sulfhydryl group of another.
- See Slide 13-17
Describe the stoichiometry of the Palmitate Synthesis Reaction
8Acetyl CoA + 7ATP + 14NADPH + 6H
= CH3(CH2)14COO- (palmitate) + 14NADP+ + 8CoA
+ 6H2O + 7ADP + 7Pi
Regulation of FAS
- Allosteric effect (presence of phosphorylated sugars)
- Induction and repression at gene level
– High carbohydrate/low fat diet increases FAS synthesis.
– High fat diet as well as starvation lowers FAS synthesis.
See Slide 20-22
Felt like this deserved it’s own slide. Although really they all do.
How is VLDL formed?
- TAG packaged with apoproteins to form Very Low Density Lipoproteins (VLDL) and secreted into blood
- See Slide 22
Describe Eicosanoids
- Eicosanoids are products generated by the oxidation of 20 carbon fatty acids (arachidonic acid).
- They are signaling molecules and serve as messenger molecules.
- Short lived molecules, serve as local hormones
- Influence many pathways involved in growth, inflammation, infection, and immunity
- Four families:
– Prostaglandins, prostacyclins, thromboxanes and leukotrienes. - See Slides 24-25
List the metabolic actions of selected eicosanoids
Just look at slide 26, she’s too quick to write all these down.
- Also see slide 27-30
Describe mechanism 1 in the synthesis of phospholipids
- Phosphatidic acid cleaved by phosphatase to form diacylglycerol (DAG).
- DAG reacts with various headgroups to form different phospholipids.
- The headgroups need to be ‘activated’ prior to this reaction.
- Choline headgroup combines with CTP to form CDPcholine (activated).
- Phosphocholine (PC) transferred to DAG to form phosphatidylcholine and CMP is released.
Describe Mechanism 2 in the synthesis of phospholipids
- Phosphatidic acid reacts with CTP to form CDP-DAG.
- CDP-DAG reacts with inositol to form PI and CMP.
- CDP-DAG may react with glycerol to produce phosphatidyl glycerol.
- The reaction of CDP-DAG with phosphatidyl glycerol forms diphosphatidyl glycerol (cardiolipin), a component of the inner mitochondrial membrane.
Describe the interconversion between PLs.
- PS is formed by exchanging ethanolamine for serine.
- PS can be reconverted to PE by decarboxylation.
- PE can be methylated to form PC.
