Metabolism 7: TAG Degradation, Fatty Acid Oxidation, Ketone Bodies Flashcards
What is HSTL?
Hormone-Sensitive Triacylglycerol Lipase: Cleaves TAGs into glycerol and 3 fatty acids in the adipose tissue
What effect does epinephrine/glucagon have on HSTL?
Stimulates and activates it.
Epinephrine works via cAMP and PKA to phosphorylate HSTL -> Activates it
What effect does insulin have on HSTL?
Antilipolytic-Inhibits activity by dephosphorylation
What effect does prostaglandin have on HSTL?
Antilipolytic- inhibits activity
What role do thyroid and adrenal cortical hormones have on HSTL?
They are permissive. Do not activate but are required for normal activity
Which part of TAG breakdown can be used to create glucose?
Glycerol
How much of total dietary caloric intake should TAG consumption comprise?
<30%
What kind of condition stimulates mobilization of TAGs?
When there is a need for substrates for energy production
What is perilipin?
Coats the surface of fat droplets. It must be phosphorylated by PKA iin order for HSTL to translocate to surface of the fat droplet and hydrolyze TAGs
What are the possible fates of released FA from TAG breakdown?
Enter circulation->bind Albumin-> carried to muscle, liver, etc -> undergo beta oxidation and energy production
What are the possible fates of glycerol from TAG breakdown
transported to kidney and liver
Phosphorylated by glycerol kinase to generate glycerol-3-phosphate for use in gluconeogenesis
What does the increased circulating levels of FAs from TAG breakdown increase?
Beta-oxidation of fatty acids
Ketone body formation
Gluconeogenesis
What does the increased circulating levels of FAs from TAG breakdwon inhibit?
Fatty acid biosynthesis
Glycolysis
How does circulating levels of FAs inhibit fatty acid biosynthesis?
Fatty-AcylCoA allosterically inhibits Acetyl-CoA Carboxylase (rxn: Acetyl-CoA ->Fatty Acyll CoA
Inhibit produciton of Malonyl CoA
What is the only physiological inhibitor of carnitine palmitoyl transferase-1?
MAlonyl CoA: product of fatty acid biosynthesis
What also increases as beta oxidation of fatty acid increases?
Ketone Body formation
How does an increase in ATP by tissues metabolizing fatty acid impact glycolysis?
It inhibits it by inhibiting PFK-1 (Signaling that we have enough ATP)
What can the increased ATP production from fatty acid metabolism be used for?
Gluconeogenesis
Which organs are good users of fatty acids?
Liver, Kidney Cortex, Heart, Skeletal Muscle
Which organs do not/cannot use fatty acids for energy?
RBCs, Brain, Nervous System, Adrenal Medulla, Lens
What is hte major energy producing pathway in the body?
Mitochondrial Beta Oxidation of Fatty Acids
What does the complete beta-oxidation of palmitic Acid produce? How much ATP?
8 Acetyl-CoA
7 NADH
7 FADH2
Total 106 ATP
What does a single cycle of beta oxidation generate?
1 Acetyl CoA, NADH, FADH2
How are fatty acids degraded?
Sequential removal of 2 carbon units
What does carnitine do?
Transports long chain fatty acids into the mitochondrial matrix for beta oxidation (Carnitine –> Acyl Carnitine)
What does an inhibition of carnitine transport result in?
Inhibited fatty acid oxidation
Decreased ATP production
What is CPT-1?
Carnitine Palmitoyl Transferase I: Transports fatty acid chains by placing them on carnitine to form acylcarnitine
What is the rate limiting enzyme for fatty acid beta oxidation?
CPT-1
How does Malonyl CoA affect CPT-1?
It is the only known inhibitor of carnitine palmitoyl trasnferase and blocks the formation of acylcarnitine
Thus it inhibits fatty acid oxidation
What is malonyl CoA a product of?
The rate limiting eznzyme Acety-CoA Carboxylase in fatty acid biosynthesis
What is Primary Carnitine Deficiency Disorder?
Defect in carnitine transporter
What is SEcondary Carnitine Deficiency Disorder?
Defect in CPT-II or CPT-I
What deficiency accounts for 10% of Sudden Infant Death Syndrome(SIDS)
Deficiency of medium chain FA-CoA Dehydrogenase
How are long, medium, and short chain fatty acids beta-oxidized differently?
They use separate AcylCoA Dehydrogenases (LCAD, MCAD, SCAD)
Where are ketone bodies formed?
ONLY in the Liver Mitochondria
What usually accompanies ketone body formation?
High rate of beta oxidation of fatty acids in liver
What are the ketone bodies?
Acetoacetate, Beta hydroxybutyrate, Acetone
Which ketone body is formed spontaneously without enzyme?
Acetone from acetoacetate via decarboxylation rxn
What is HMMG-CoA Synthase?
Mitochondrial enzyme only found in liver that acts in ketone body formation
Does the liver also use ketone bodies for energy?
No. They do not have the acetoacetate:succinyl-CoA Transferase enzyme (thiophorase) for ketone utilization
What happens to the ketone bodies once they are formed?
generated in liver -> released into circulation -> transported to other tissues (mitochondria of muscle, brain, etc) for energy production
