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57 Cards in this Set

  • Front
  • Back
What are two beneficial features of fatty acids as a stored fuel?
a. Highly reduced = more energy.
b. Not hydrated = tightly packed.
How are fats stored?
triacylglycerols (TAG)
What is the first step in the breakdown of TAGs?
Bile salts (glycocholate), make fats soluble.
a. What do lipases do to fats?
b. Which two lipases act on TAG and in what order?
.
a. Hydrolyze the TAGs to monoacyglycerol and fatty acids.
b. pancreatic -> intestinal
.
a. After digestion of TAGs by lipases, what do you have and
b. Where does it go?
.
a. monoacylglycerols and fatty acids.
b. absorbed through intestinal wall.
.
What happens after monoacylglycerols and fatty acids are absorbed by the intestines?
.
They are converted back to TAGs and incorported into small particles known as chylomicrons (apolipoproteins... other lipoproteins include HDLs and LDLs).
.
Which fatty acids (in terms of length) require special transport (chylomicrons)?
.
long chain
what causes lipoprotein lipase to breakdown the TAGs in the chylomicrons?
Apo C-II, which is in the chylomicron.
In tissue, where the TAGs are being broken down to fatty acids by lipoprotein lipase, what happens to the fatty acids?
.
They now can enter the cells.
.
What is the fate of fats stored adipocytes?
re-esterfied to for storage.
What are re-esterfied fats?
TAGs.
Summarize Stage I of the utilization of fatty acid fuels.
.
1. TAGs are hydrolyzed to fatty acids in the adipocytes
2. released then transported by albumin to tissues requiring energy.
.
Summarize Stage II of the utilization of fatty acid fuels.
.
Fatty acids are activated and transported into the mitochondria.
.
Summarize Stage III of the utilization of fatty acid fuels.
.
Fatty acids are broken down by ß-oxidation (a step by step process).
.
what are the hormones that release fatty acids from adipocytes?
.
•Glucagon
•ACTH
•epinephrine
.
Detail the events leading up to and including Phase I of the utilization of fatty acids: release and transport from adipocytes.
.
1. hormone (e.g., glucagon, ACTH, epinephrine) attaches to a receptor.
2. cAMP is generated
3. activation of cAMP dependent protein kinases.
4. phosphorylation (activation) of TAG lipase by kinase.
5. TAG lipase 6. breakdown of TAG to DAG...
6... leading to 3 fatty acids and a glycerol.
6. fatty acids are transported by serum albumin.
.
What is the name of the enzyme found on mitochondria that converts fatty acids to fatty-CoA?

BIG PICTURE: why are we doing this?
acyl-CoA Synthase

We are going to utilize fatty acids for energy
a. What is fatty acid and ATP converted to?
b. What is the enzyme for this rxn.
c. What is unusual about the product of this rxn?
d. What is the goal here?
.
a. Acyl adenylate + PPi
b. acyl-CoA synthase.
c. Most of the time the gamma phosphate that is transferred, here it is the AMP.
d. to convert fatty acid to Acyl-CoA so it can be transported into the mitochondria... thus, acyl adenylate + CoA --> Acyl-CoA is formed and then transported into the outer membrand of the mitochondria.
.
The rxn: R-COO + ATP + CoA --> acyl CoA + AMP + PPi: ∆G° = -.2, but ∆G = -8.4, why?
.
the rxn is coupled with the hydrolysis of Pyrophosphate (PPi --> Pi + Pi).
What happens immediately after the acyl-CoA enters the intermembrane space?
.
CPT-I converts the acyl-CoA + carnitine into acyl-carnitine, which can now pass through the inner mitochondrial membrane.
.
Where is CPT-1 located?
.
On the outer mitochondrial membrane (facing the intermitochondrial space).
.
What happens to the acyl-carnitine?
after it pass through the inner mitochondrial membrane is converted back into acyl-CoA + carnitine.
What drives the carnitine, recently separated from the acyl out of the mitochondrial matrix?
.
the ß-oxidation of the acyl, the continued transport of acyl-carnitine and thus the growing concentration of carnitine.
.
Where is CPT-II?
on the inner mitochondrial membrane, facing the matrix.
.
Which fatty acyl need carnitine to enter the matrix?
.
long chains (>12-C)
.
a. Which organs rely heavily on the ß-oxidation of fatty acyl for energy production.
b. What is generally the cause of clinical deficiency in ß-oxidation?
.
a.
• skeletal muscle
• heart
• liver
b. CPT-II is not functional, thus acyl-carnitine gets into the matrix but it's not converted efficiently or at all.
.
What are the symptoms of adult onset CPT-II deficiency?
.
• muscle pain
• rhabdomyolysis (muscle breakdown)
• myoglobinuria
What trigger the symptoms of adult onset of CPT-II?
.
pain and some of these other symptoms are triggered by exercise, fasting, infections, exposure to cold.
.
What are the symptoms of neonate onset of CPT-II?
.
• heart arrhythmias
• seizure, coma
.
Which is more severe CPT-II in adult or neonates, why?
.
a. Neonate
b. extreme and ubiquitous build up of acy-carnitine in the cells and the plasm has a negative effect on heart function.
c. effects uptake of carnitine.
.
what four enzyme are required for ß-oxidation? and which is most important?
• thiolase (most important, it breaks the C-bonds)
• acyl-CoA dehydrogenase
• enoyl-CoA hydrotase
• L-hydroxyacyl-CoA dehydrogenase
.
a. What is the role the following enzymes in ß-oxidation?
• acyl-CoA dehydrogenase
• enoyl-CoA hydrotase
• L-hydroxyacyl-CoA

b. What happens next?
.
a. To introduce a carbonyl at the ß-carbon... converting all acyl CoA to acetyl CoA.

b. thiolase can then catalyze the breakdown of acetyl-CoA after each cycle.
.
How many acetyl-CoAs do you get from a 16-carbon molecule?
8
What is required for the break down of a 16-carbon acyl and what is produced?
.
• Required:
7-FAD+
7-NAD
7-CoA
7-H2O

• Produced:
8-acetyl-CoA
7-FADH2
7-NADH
7-H+

If all of the products go through the 130 H2O are produced???
.
How many ATPs do you get from the breakdown of one 16-carbon acyl?
.
108 ATP (6.75/carbon)

(acetyl CoA is going throught TCA cycle with the NADH and FADH2 produced in the cycle... in addition more NADH and FADH2 is being produced through ß-oxidized).
.
What is the significance of ß-oxidation of fatty acyl as it relates to water?
.
The process produces 130 water molecules.
.
Why are saturated fatty acids bad for you?
.
They precipitate out and clog arteries.
.
What other uses do acetyl CoAs have besides the TCA cycle?
.
Some are converted to ketones metabolites.
Name three acetyl CoA metabolites (which one is not really a ketone?)
.
• acetone
• acetoacetate
• D-3-hydrobutyrate (not a ketone)
.
Where are ketones made from acetyl CoA?
ONLY in the Mitochondrial Matrix of the Liver.
.
What is the rxn dynamic of the following ketones?
• acetoacetate
• acetone
• D-3-hydrobutyrate
.
• acetoacetate in equilibrium with D-3-hydrobutyrate (production of acetoacetate from D-3-HB is NAD dep.)
• acetoacetate is converted to acetone
.
Besides clipping of the final acetyl CoA in ß-oxidation, what does thiolase do in ketone synthesis?
.
Thiolase catalyzes the conversion of 2 acetyl-CoA into on acetoacetyl-CoA... and vice versa... so thiolase is important in the conversion and utilization of ketones to and from acetyl CoA
a. What is the fate of acetoacetyl-CoA?
b. What catalyzes this process?
a. it is converted to HMG CoA.
b. HMG CoA synthase
a. What is the fate of HMG CoA?
b. What catalyzes this process?
a. it is converted to acetoacetate.
b. HMG CoA lysase
a. In the equlibrium of acetoacetate to hydroxybutyrate, what drives the rxn to hydroxybutyrate.

.
a. High [NADH]= hydroxybutyrate... low [NADH] = acetoacetate
What is the fate of acetone?
.
Of no energy use, thus it is excreted.
.
What tissues/organs prefer ketones as an energy source?
.
• Kidney cortex
• heart muscle.
• peripheral tissues during periods of fasting or starvation.
.
Ketones are small, do they need help in blood transport?
.
no.
.
What is the range of ratio between... hydroxybutyrate: acetoacetate?
.
1:1 to 10:1 in favor of hydroxybutyrate.
.
Why would find hydroxybutyrate and acetoacetate circulating through the blood?
.
They can be converted to acetyl-CoA and thus they are a fuel source.
.
Can acetoacetate be directly reactivated?
.
no only as part of cholesterol synthesis.
.
A. Describe the 2 steps in ketone utilization, which converts acetoacetate into 2 acetyl CoA in the mitochondrial martrix... include enzymes and other requirements?

B. Which is the rate limiting step?
.
STEP I:
a. acetoacetate --> acetoacetyl CoA
b. requires
• CoA transferase
• Succinyl CoA
A:
STEP II:
a. acetoacetyl CoA --> 2 each of acetyl CoA
b. requirements:
• thiolase
• CoA (for the second acetyl CoA.)

B. STEP I
a. Where did the succinyl come from in the reactivation of acetoacetate CoA?
b. is GTP produced in this use of succinyl CoA?

.
a. It is siphoned off of the TCA cycle.
b. no
a. At what level does the blood become saturated with ketones? (ketonemia, ketonuria)
b. in which people is this common?
.
a. 12mM
b. dieters
.
What danger is involved in increased blood ketone concentration?
.
blood loses its buffering capability resulting in the lowering of pH.
.
a. Which hormones regulate ketogenesis?
b. Which hormone is the hormone of fasting?
.
a. glucogon, ACTH, and epinephrine releases fatty acids from adipocytes.

b. Glucagon (targets the liver... opposed by insulin.)
.
Name the 3 points of regulation for ketones.
1. Hormones

2. Uptake of fatty acids: Malonyl-CoA (inhibits CPT-I)

3. the acetyl-CoA is used in the TCA cycle instead of ketogenesis, where as the level of serum ketones increase more free fatty acids are converted to ketones. And as NADH increase the TCA cycle slows down and ketones are preferentially made in its place.
.