lipid biosynthesis

Question 1

9 biological functions of lipids

Answer 1

1. Energy storage (TG)
   
   2. Constituents of membranes
   3. Anchors for membrane proteins (IP2/IP3)
   4. Cofactors for enzymes (vit k)
   5. Sigaling molecules (eicosanoids, IP3)
   6. Pigments (retinal)
   7. Detergents (bile salt)
   8. Transporters
2. Antioxidants (vitA)

Question 2

phase 1: formation of the malonyl-coa from acetyl-coa

Answer 2

Acetyl-CoA carboxylase has 3 functions:
1. Biotin carrier protein (gray) (Biotin bound to the amino group of a lys residue by amide linkage)
2. Biotin carboxylase, which activates CO2 by attaching it to a nitrogen in the biotin ring in an ATP-dependent reaction
Transcarboxylase, which transfers activated CO2 (green) from biotin to acetyl-coa, producing malonyl-coa

Question 3

what are the precursors of longer FA + what is synthesized

Answer 3

• long FA chain are produced in the ER (also mitochondria)
• palmitate is the precursor for long-chain FA
• plamitate (16:0) and stearate (18:0) are desaturated by Fatty acyl-coa desaturase by oxidative reaction
• Palmitoleate (16:1) and oleate (18:1) have double bonds at C9-C10
• Linoleate (18:2triangle9,12) canno be synthesize in mammals (essential)
  Arachidonate is synthesized from linoleate

Question 4

regulation of biosynthesis of FA (step for the transport of acetyl-coa from mito to cytoplasm..)

Answer 4

1. Pyruvate derived from AA catabolism in the mitochondrial matrix or from glucose by glucolysis in the cytosol and will be converted into acetyl-coa in the matrix
   
   2. Acetyl groups pass out the mitochondria as citrate (acetyl-Coa + oxaloacetate = citrate by the citrate synthase)
   3. In the cytosol, citrate is delivered as acetyl-coa (citrate + oxaloacetate= acetyl-Coa) for FA synthesis
   4. Oxaloacetate is reduced to malate in the cytoplasm by malate dehydrogenase, which can :
      - return to the mitochondrial matrix (by a-ketoglutarate transporter) where it will be reconvert to oxaloacetate by malate dehydrogenase
      It stays in the cytoplasm where it will be oxidized by malic enzyme to create a pyruvate and some NADPH. Then the pyruvate returns to the mitochondrial matrix where it will be transform into oxaloacetate by pyrvutae carboxylase

Question 5

what inhibit or activate biosynthesis of FA

Answer 5

• Acetyl-coa carboxylase (which is the first step for the synthesis of FAis the rate limiting enzyme
  
  • Inhibited by phosphorylation by epinephrine and glucagon signal
  • Palmitoyl-coa is a feedback inhibitor
    Citrate from mitochondria is an activator

Question 6

catabolism vs anabolism of FA

Answer 6

Catabolism:

- PRODUCES acetyl-coa
- PRODUCES electron donors (NADH)
- Take place in the MITOCHONDRIA

Anabolism:

- REQUIRES acetyl-coa and malonyl-coa
- REQUIRES electron donor NADPH - Takes place in CYTOSOL in animals

Question 7

what happens during biosynthesis of FA

Answer 7

1. First, we need an acetyl-coa (not active) present in the cytoplasm which is capture by the KS domain
   
   2. ACP is something that carries chains that are synthesized so it will then get with the help of MAT the activated malonyl-coa
   3. The carboxyl group of the malonyl-coa will link to the acetyl-coa attaches to the KS domain so the result is that malonyl-coa has 2 more carbons on it so the chain grows (2 carbons at a time) ** acetyl-coa and malonyl-coa are attaches to ACP which is an important domain bc it is where chain grows + receive malonyl-coa
      * * many of the carbons have double bonds and oxygen but FA are supposed to have no double bonds + H
   4. A lot of reduction process where we add hydrogen to reduce carbons (no double bonds)
   5. FA chain has to be transferred to KS domain so ACP is free to receive another malonyl-coa

Question 8

2 process promotes by insulin

Answer 8

1. synthesize of FA

2. storage of FA by synthesis of TG

Question 9

regulation of FA synthesis and B-oxidation (what happens when high and low glucose)

Answer 9

1. Glucose is catalyzed throug glycolysis which leads to acetyl-coa
   
   • Insulin leads to activation of phosphatase enzyme which is going to dephosphorylase ACC and thus activated: acetyl-coa can be activated to malonyl-coa which leads to FA synthesis
     2. Low glucose increase glucagon which is a GPCR which activates PKA and it will phosĥorylase ACC and desactivated it because they need energy so dont want to synthesis FA but using it for energt

** lot of malonyl-coa means that the cells have sufficient enrergy so it can inhibit the enzyme responsible for the transport of FA to mitochondria (carnitine) (the beginning of the oxidation), so it ill be inhibited since they dont need energy

** insulin promotes FA synthesis

Question 10

synthesis of TG (for storage)

Answer 10

1. Need the glycerol which comes from the glycolysis or from the release of the glycerol from FA
   
   2. Glycerol is converted to glycerol-3-phosphate by glycerol 3-phosphate dehydrogenase
   3. The acylk transferase will add FA to the glycerol (where the phosphate groyup is on the third carbon) = creation of phosphatidic acid which is compose of 2 FA, one glycerol and one phosphate group
      The phosphatidic can be convert to membrane lipids such as glycerolphospholipids or they become structural lipids if they are acted with proteins or carbohydrate molecules so they will go to the membrane. On the other hand, phosphatidic acid can loose its phosphate (by the enzyme phosphatidic acid phosphatase) and become diacylglycerol so it will permit another FA to come in (by acyl transferase which is the enzyme that take FA and add it to the glycerol backbone) = triacyglycerol which can now be stored

Question 11

biosynthesis of cholesterol

Answer 11

1. Conversion of acetate to HMG-COA by HMG-CoA synthase
   
   2. Conversion to mevalonate by HGM-COA reductase

Don’t have to know all the process!! Only the conversion of acetate to mevalonate with the enzymes implied which are then phosphorylated, cyclase and polymerase to create cholesterol

Question 12

HGM-CoA reductase is rate limiting enzyme (what inhibits + activate it)

Answer 12

1. AMP-dependent protein kinase
   
   • When AMP rises, AMPK phosphorylates the enzyme = decrease the activity, cholesterol synthesis decrease
     2. Glucagon, epinephrine:
   • Cascade leads to phosphorylation (PKA pathway)= decrease the activity
     3. Insulin:
   • Cascade lead to dephosphorylation, increase activity
     4. Insig (insulin-induced gene protein) senses cholesterol levels
   • Triggers ubiquination of HMG-CoA reductase
     5. SREBPs (sterol regulatory element binding proteins) activate HMG-CoA reductase
2. Statins (lipitor): HMG-CoA reductase inhibitot to treat high cholesterol