29 - Lipid Metabolism II Flashcards
A typical 70 kg (154 lbs) man fuel stores:
- _____ kCal Glucose (blood)
- _____ kCal in Glycogen (liver and muscle)
- _____ kCal in Protein (muscle)
- _____ kCal in TAGs (in fat and muscle)
40
600
24,000
100,000
Pound for pound TAGs contain about ______ times as much energy as Carbs (i.e. Glycogen)!
6.75
This is the major storage form of fatty acids.
TAGs (Triacylglycerols)
What are TAGs composed of?
Glycerol
3 FA chains
A glycerol attached to one FA chain is called…
Monoacyl glycerol (MAG)
A glycerol attached to two FA chains is called…
Diacyl glycerol (DAG)
Dietary TAG is processed in…
Intestinal cells
De Novo TAG is in __________ and __________.
Hepatocytes
Adipocytes
In the mobilization of FA from adipocytes, it times of hunger the hormone _________ is released and in times of exercise the hormone _________ is released. These bind to a GPCR which goes on to activate Protein Kinase A (PKA) from cAMP. PKA then phosphorylates ________ and _______.
Glucagon
Epinephrine
Perilipin
HSL (hormone sensitive lipase)
Perilipin associates with ________ and ________ to promote lipolysis so free FAs can be released and go into the blood.
ATGL (adipose triglyceride lipase)
HSL (hormone sensitive lipase)
What acts on MAG to release FFAs?
MAG lipase
In a fed state, ________ is released and attaches to a receptor RTK. It promotes the activity of _______ _______ which dephosphorylates and inactivates HSL. This keeps FFAs from being released.
Insulin Protein Phosphatase (PP1)
These surround lipid droplets to prevent their breakdown. When they get phosphorylated, they loosen.
Perilipins
These are a family of proteins that coat lipid droplets in adipocytes and muscle cells. They regulate lipolysis by controlling physical access to lipid breakdown enzymes.
Perilipins
Perilipins are regulated by ______, and phosphorylation allows association with HSL which promotes lipolysis.
PKA
Overexpression of Perilipin 1 inhibits lipolysis and its knock-out has converse effect. This is a target of ________ treatment.
Obesity
FAs are broken down by means of Beta-oxidation inside the _________, while they are synthesized outside of this in the ________.
Mitochondria
Cytosol
Long-chain fatty acids are always complexed with ________ so they don’t clot.
Albumin
In phase 1 of FA breakdown, FA activation must occur in the cytosol. ______ and ______ activate the FA with the help of enzyme acyl-CoA synthetase, forming _________.
ATP
CoA
Acyl CoA
T/F. In the activation phase of FA degradation, ATP is broken down into ADP.
False. It’s broken down into AMP + PPi.
What makes the activation step of FA degradation irreversible?
PPi hydrolysis
The outer mitochondrial membrane is impermeable to what?
Fatty acids
The inner mitochondrial membrane is impermeable to what?
Fatty acyl CoA
In FA degradation, once fatty acyl CoA is formed then carnitine is used along with the enzyme _______ _______ to form ________ ________.
Carnitine acyltransferase I
Acyl carnitine
Acyl carnitine is able to move across the outer mitochondrial membrane through pores and across the inner mitochondrial membrane using _________.
Translocase
Once the acyl carnitine is inside the mitochondrial matrix, the enzyme _________ _________ splits it back into carnitine and acyl CoA. Carnitine is then transported back out to be used again.
Carnitine acyltransferase II
What is the rate limiting step of FA degradation?
Carnitine acyltransferase I
The rate limiting step of FA degradation is carnitine acyltransferase I. What can this step be inhibited by and why?
Malonyl CoA, because if there is a lot of Malonyl CoA around that means FAs are being synthesized, so we don’t want to degrade them.
In phase II, there are 4 steps of Beta-oxidation within the mitochondria, which includes what type of mechanisms?
1) Oxidation
2) Hydration
3) Oxidation
4) Thiolysis
Step 1 of Beta-oxidation includes ________ ________ oxidizing the Beta-carbon to produce _______ and ________.
Acyl CoA dehydrogenase (ACAD)
FADH2
Trans-enoyl-CoA
In step 1 of Beta-oxidation, the FADH2 produced enter the ETC (goes to CoQ) to generate ______.
2 ATP
Step 2 of Beta-Oxidation includes _______ _______ saturating the alkene of trans-enoyl-CoA with water to form _______ _______.
Enoyl CoA hydratase
Beta-hydroxyacyl CoA
Step 3 of Beta-oxidation includes ________ ________ oxidizing the carbon to form ________ and ________.
Beta-hydroxyacyl CoA dehydrogenase
Ketoacyl CoA
NADH
In step 3 of Beta-oxidation, the NADH produced enters the ETC (goes to complex I) to generate _______.
3 ATP
Step 4 of Beta-oxidation includes ________ ________ or _________ which attaches to the sulfur of CoA to ketone formed from cleavage of acetyl CoA from fatty acyl chain which is shortened by 2C.
Acetyl CoA Acyltransferase
Ketothiolase
This group of 4 reactions of Beta-oxidation is completed until the entire ______ is broken down to _______, which enters the TCA cycle.
FA
Acetyl CoA
What do the four main steps of Beta-oxidation generate?
FADH2
NADH
Acetyl CoA
The degradation of palmitoyl CoA requires _____ reaction cycles. In the last cycle, the C4 compound is thiolyzed to 2 acetyl CoA.
7
What is the equation for the degradation of palmitate?
Palmitoyl CoA + 7FAD + 7NAD+ + 7CoA + 7H2O = 7FADH2 + 7NADH + 7H+ + 8 Acetyl CoA
How many total ATP are produced from the FADH2 and NADH in the degradation of palmitate?
FADH2 = 14 ATP (7 x 2 = 14) NADH = 21 ATP (7 x 3 = 21)
How many total ATP are produced from the Acetyl CoA in the degradation of palmitate?
96 ATP (8 x 12 = 96)
What is the net ATP produced for the degradation of palmitate?
129 ATP
***131 ATP made, 2 used during the activation of palmitate, 129 net ATP
Acetyl CoA formed from FAs enters the TCA cycle. Here it combines with _________ to form ________.
Oxaloacetate (OAA)
Citrate
If OAA is low (due to low carb) acetyl CoA can not be utilized. In fasting or diabetes OAA is converted to ________ by _________.
Glucose
Gluconeogenesis
Excess unused Acetyl CoA condenses to form…
Ketone bodies
Ketone bodies are water-soluble and acidic compounds. There are 3 types, which are…
Acetoacetate
Beta-Hydroxybutyrate
Acetone
Ketone bodies are produced only in the _______ and provide energy for peripheral tissues and the brain during fasting/starvation.
Liver
In a starving state, no glucose/glycolysis occurs. This hunger triggers TAGs to breakdown (GPCR, etc.) then FAs breakdown into a lot of ________ which in turn creates ketone bodies.
Acetyl CoA
This ketone body is a precursor for the other two types.
Acetoacetate
T/F. Acetoacetate can be reversed back into acetyl CoA.
True
In times of starvation, ketone bodies can be transported in the blood to other cells (Heart-muscle, renal cortex, brain) and broken back down into acetyl CoA. This acetyl CoA then does what?
Enters the TCA cycle to produce energy.
In diabetic ketoacidosis (DKA), diabetics have glucose but don’t have GLUTs (transporters) so the glucose can’t enter tissues. Low glucose triggers adipose tissue to start the breakdown of TAGs to free fatty acids. These FAs then go to the liver and are further broken down to acetyl CoA but due to low OAA, _______ _______ are formed. Due to the person being diabetic, the ketone bodies (acidic) made are in such high concentration that the blood pH drops which ultimately leads to coma and death.
Ketone bodies
