Lipid Metabolism II Flashcards
Describe the energy storage of the body
- blood has 40 Kcal of glucose
- 600 Kcal of glycogen in the liver and muscle
- 24,000 kCal of protein in the muscle
- 100,000 kCal in TAGs
TAGS have 6.75 times as much energy as carbs (glycogen)
Describe the structure of Triacylglycerol including the various sources of TAGs
Glycerol backbone with 3 fatty acid chains.
can get TAGs from diet (from intestinal cells)
De novo TAG in both hepatocytes and adipocytes
Describe the mobilization of fatty acids from adipocytes in detail (Hunger phase)
In a state of hunger, glucagon and epinephrine are released and go to stimulate a GPCR which leads to a release of cAMP from adenylate cyclase, activating Protein kinase A.
Protein kinase A activates Perilipin via phosphorylation which activates ATGL(adipose triglyceride lipase) that takes the TAG to a DAG
Protein kinase A is also able to phosphorylates HSL (hormone sensitive lipase) that takes the DAG to MAG
MAG lipase takes the MAG to a glycerol and fatty acid form
Describe the mobilization of fatty acids from adipocytes in a fed state.
In a fed state, you are getting your fatty acids from your diet so you do not need to make any more. SOOO the insulin receptor triggers the protein phosphatase which dephosphorylates and inactivates HSL Which does not allow the DAGs to get to the MAGs
What is a perilipin
family of proteins that coat lipid droplets in adipocytes and muscle cells
This coating helps to regulate the amount of lipid breakdown molecules get in due to decreased physical access
How are perilipins regulated?
regulated by PKA that phosphorylates HSL that promotes lipolysis
What happens if there is an over expression of perilipin 1? What about a knock out?
Overexpression inhibits lipolysis and the knockout does not inhibit
Describe the permeability of the outer and inner mitochondrial membranes
Outer membrane is NOT permeable to fatty acids
Inner membrane is NOT permeable to FaCoA
Briefly describe the phases of Fatty acid breakdown including the locations
Phase 1 is the activation of fatty acids and occurs in the cytosol
Phase II is Beta oxidation and occurs in the matrix
Describe phase I of fatty acid activation
First reaction in any FA metabolism and occurs INSIDE The cytoplasm
Uses Acyl CoA synthetase
Traps fatty acids in the cells
Makes it metabolically active
Is irreversible because of PPi hydrolysis
Describe the translocation into the mitochondrial matrix
Carnitine is able to go the the cytoplasmic side where Acyl CoA acts with carnitine acyltransferase I to make acyl carnitine
acyl carnitine is able to translocate through to the matrix and carnitine acyltransferase II is able to spit out an Acyl CoA with the help of CoA
Describe phase II of lipid breakdown
Beta oxidation phase has 4 steps
- oxidation via the acyl CoA dehydrogenase (ACAD)
- Hydration via the enoyl CoA hydratase
- Oxidation via 3-hydroxyacyl CoA dehydrogenase
- Thiolysis via Acetyl CoA Acetyltranferase
This repeats until the entire fatty acid is broken down
What is the function of ACAD
Acyl CoA dehydrogenase is involved in the first step of beta oxidation and oxidizes the beta carbon to produce FADH2 and trans-enoyl-CoA. FADH2 enters the ETC to generate 2 ATP
What is the function of enoyl CoA hydrates?
Involved in the second step of B oxidation
Uses water to saturate the alkene to form B hydroxy acyl CoA
What is the function of B hydroxy acyl CoA dehydrogenase?
Involved in the third step of B oxidation and oxidizes carbon to form ketoacyl CoA and NADH which is able to enter the ETC to generate 3 ATP
What is the function of acyl CoA acyl transferase (ketothiolase)
involved in the fourth step of beta oxidation and attaches a sulfur of the coA to a ketone formed from cleavage of acetyl CoA from fatty acyl chain which is shortened by 2 C’s.
Describe what the 4 main steps generate
FIRST(step): ACAD that oxidizes the fatty acid releases FADH2 that takes the electrons to the CoQ enzyme of the ETC
THIRD: B hydroxy acyl CoA dehydrogenase releases NADH during its oxidation reaction. The NADH delivers its electrons to Complex 1 of the ETC
FOURTH: acetyl CoA is released which is able to enter the TCA cycle
Given that the number of reaction cycles that are required in order to break down palmitic acid in Beta oxidation,,
What is the amount of ATP that would be gained from
1. FADH2
2. NADH
3. Acetyl CoA
Total ATP and the net ATP
- 2 ATP are formed from FADH2
- 3 ATP are formed from NADH
- 8 acetyl CoA are formed (because two are made in the seventh step; 6+2=8)
FADH2 yields 14 ATP NADH yields 21 ATP Acetyl CoA yields 96 ATP Total is 131 ATP but w ATP are used in the activation of palmitate, which means NET= 129
Describe the links that are present between lipid and carbohydrate oxidation
- acetyl CoA is formed from the fatty acids enters the TCA cycle
- Acetyl CoA combines with OAA to form citrate BUT if the level of carbs is low, then the level of OAA will also be low
- “Fats burn in the flame of carbohydrates”
Describe what happens to excess unused acetyl CoA
condenses to form ketone bodies
Who are ketone bodies?
Water soluble and acidic compounds that are produced only in the liver
-provide energy for peripheral tissues during fasting and brain during starvation
Describe what happens to the body during fasting and starvation
Fatty acids will be broken down and increase the amount of acetyl CoA that will be able to go to the TCA cycle and the fatty acid derivatives can be used to make ketone bodies that provide energy for the rest of the body during times of fasting and starvation
Describe the formation of ketone bodies in detail
two acetyl CoA molecules combine to make acetoacetyl CoA
Another acetyl CoA is added to form 3-hydroxy-3-methyl-glutaryl CoA with the help of water
acetyl CoA is removed to form acetoacetate
acetoacetate is broken down into acetone and D-3-hydroxy-butyrate (this step oxidizes NADH to NAD+)
Describe how 2 acetyl CoA are able to be derived from acetoacetate
CoA transferase takes Acetoacetate to acetoacetyl CoA with the help of succinylcholine CoA (yields succinate)
Thiolase adds another CoA to create 2 acetyl CoA molecules
