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L 67 TAG Degradation,, FA Oxidation, and Ketone Bodies
n/a
20
Physiology
Graduate
04/10/2012

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Term
Identify the physiological conditions and hormones that activate the mobilization of fatty acids from triacylglycerols and hence lead to elevated circulating levels of fatty acids. These fatty acids can be used for Beta oxidation.
Definition
- When there is a need for ATP (energy)/ fasting state
- epinephrine (major) and ACTH (minor) mobilize fatty acids by activating HSTL: Hormone Sensitive Triacylglycerol Lipase
-HSTL is activated by cAMP dependent protein kinase A
Term
Identify the physiological conditions and hormones that inhibit adipose tissue HSTL and hence lead to reduced levels of circulating fatty acids. Reduced levels of circulating fatty acids would reduce beta-oxidation of fatty acids.
Definition
-High energy/fed state
- insulin inhibits the mobilization of fatty acids by inhibiting HSTL: Hormone Sensitive Triacylglycerol Lipase through dephosphorylation
-Prostaglandins inhibit HSTL also
Term
Predict the impact of mobilization of fatty acids from adipose tissue triacylglycerols on each of the following pathways: beta oxidation of fatty acids, ketone body formation, fatty acid biosynthesis, glycolysis, and gluconeogenesis.
Definition
***Beta oxidation of fatty acids: increases, free fatty acids for energy production and malonyl-CoA (the only inhibitor) is reduced by reduction of fatty acid biosynthesis
***ketone body formation: increase, increased by increase in fatty acid oxidation
***fatty acid biosynthesis: inhibits, ACoA carboxylase is inhibited by fatty acid increase
***glycolysis: inhibits, increased ATP inhibits PFK-1
***gluconeogenesis: activates, increased ATP facilitates it
Term
Identify the tissues that are good users of fatty acids as an energy source and those tissues that cannot use fatty acids.
Definition
Good Users: Liver, kidney cortex, heart, skeletal muscle
Cannot Use: brain, nervous system, red blood cells, adrenal medulla, lens
Term
Identify the products that are formed in each cycle of fatty acid oxidation.
Definition
FADH2, NADH, and Acetyl-CoA
Term
Compare the relative amount of ATP that can be generated from metabolism of palmitate to CO2 and H2O with that generated from the metabolism of glucose to CO2 and H2O. Include the reoxidation of any NADH (␣beta-oxidation and glycolysis) or FADH2 (beta␣-oxidation) formed in the process.
Definition
palmitate metabolism: 106 ATP
glucose metabolism: 32 ATP
Term
Explain the functions of carnitine, carnitine palmitoyl transferase I and II (CPT-I & CPT -II) in fatty acid transport and beta-oxidation of fatty acids.
Definition
carnitine:: compound that transports fatty acids from cytosol into mitochondria
CPT1:: rate limiting enzyme; enzyme with transferase activity that conjugates carnitine to Acyl-CoA
CPTII::enzyme with transferase activity that converts acyl-carnitine to Acyl-CoA so that it can go through B-oxidation
Term
Predict the physiological consequences of a deficiency of carnitine or a defect in CPT-I or CPT-II on fatty acid oxidation, ATP formation, and gluconeogenesis.
Definition
decrease in metabolism pathways because there will be decreased production of ATP
Term
Identify the rate-limiting enzyme of beta-oxidation of fatty acids and the only physiological inhibitor of this enzyme. Describe the physiological condition that favors formation of this inhibitor
Definition
rate limiting enzyme:: CPT-I
inhibitor:: malonyl CoA (produced in FA biosynthesis)
conditions that favor the inhibitor:: fed state; insulin and citrate stimulate acetyl CoA carboxylase the enzyme of the reaction that produces malonyl CoA
Term
**Predict the consequences of high blood glucose on the activity of carnitine palmitoyl transferase-1 and fatty acid oxidation. Explain the rationale for your prediction.
Definition
High blood glucose would lead to decrease in activity of CPT-I and fatty acid oxidation because this would cause fatty acid synthesis to occur which would increase levels of the inhibitor, malonyl-CoA.
Term
Predict the consequences of increased fatty acid mobilization from adipocyte triacylglycerols on oxidation of fatty acids. Explain the rationale for your prediction
Definition
Increased Fatty Acid Oxidation because malonyl CoA is reduced because fatty acid biosynthesis is decreased and there is more free fatty acids (substrates) to oxidize
Term
Explain the relationship of activation of HSTL, mobilization of fatty acids, and beta-oxidation of fatty acids to the production of ketone bodies
Definition
Ketone bodies are formed in liver mitochondria when there is a high rate of B-oxidation of Fatty Acids
Term
Compare the physiological (and hormonal) conditions that lead to increased production of ketone bodies with those that are accompanied by low production of ketone bodies.
Definition
increased production:epinephrine and low ATP
decreased production: insulin and high energy state
Term
Compare the relative utilization of ketone bodies by brain in the fed state and during starvation.
Definition
fed state: low ketone body utilization by brain
starvation: brain will utilize ketone bodies so that they may be converted to Acetyl-CoA and be used in the CA cycle for energy
Term
Explain why liver is the only tissue in which ketones can be synthesized.
Definition
HMG-CoA synthase is the rate limiting enzyme in ketone synthesis and is found only in the liver
Term
Explain why liver cannot utilize ketone bodies as a source of energy
Definition
Liver does not contain the enzyme that breaks down ketone bodies for energy; Acetoacetate:succinyl-CoA
CoA transferase
Term
Explain why liver cannot utilize ketone bodies as a source of energy
Definition
Liver does not contain the enzyme that breaks down ketone bodies for energy; Acetoacetate:succinyl-CoA
CoA transferase
Term
Identify the end product of ketone body degradation
Definition
2 Acetyl-CoA
Term
Compare the physiological conditions under which fatty acids are oxidized with those under which they are synthesized
Definition
oxidized::decreased energy state; starvation
synthesized:: energy state; fed state
Term
Beginning with triacylglycerol as the precursor, list the three steps at which ketogenesis is regulated. Identify the hormone(s) and physiological conditions that activate and inhibit each of these steps
Definition

1. HSTL (+epinephrine, -insulin; +fasting state); TAG Degradation

2. Acetyl-CoA Carboxylase (+citrate, insulin; -glucagon, epinephrine, fatty acyl-CoA; +fed state); FA Biosynthesis/produces only inhibitor of FA Oxidation (malonyl CoA)

3. CPT I (-malonyl CoA; +fasting); FA Oxidation

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