What does hormone sensitive lipase do?
liberates a fatty acid from glycerol in adipocyte
Activated by: glucagon, epinephrine, and norepinephrine
Inhibited by: insulin
What does Fatty Acyl CoA Synthetase do?
adds CoASH to a fatty acid to make Fatty Acyl CoA (different synthestases for different length chains)
How do fatty acids enter the inner mitochondrial matrix for beta oxidation?
The carnitine shuttle
Carnitine palmitoyl transferase 1 (CPT1) takes off acetyl coA and add carnitine (malonyl CoA is an allosteric inhibitor)
One carnitine is added it can be transported across inner mitochondrial membrane through anti-port with a carnitine molecule
One in inner mitochondrial matrix CPT II takes off carnitine and adds aetyl CoA from mitochondrial pool
Describe the process of beta-oxidation
1. Oxidation by Acyl-CoA dehyrdogenase, electrons transferred from alpha carbon to FAD to make FADH2
2. Hydration by enoyl-CoA hydrase (H20 saturates double bond adding alcohol to the beta carbon)
3. Oxidation by Hydroxyacyl-CoA dehydrogenase (alcohol on beta carbon gets oxidized to make double bond between them)
Altered metabolism in cancer
PK-M2 varients bind another molecule that boots off the activator decreasing enzyme activity so glycolysis intermediate can be utilized by growing cell
Lactate dehydrogenase converts pyruvate to lactate under anaerobic conditions
Lactic Acidosis- accumulation of lactic acid from glycolysis under anaerobic condition can lower pH of tissues/ blood
What is medium chain acyl-CoA dehydrogenase deficiency?
Inability to oxidize medium chain fatty acids in the first step of beta oxiation
Symptoms: Reye syndrome, fasting hypoketotic hypoglycemia, hepatic ancephalopathy, SIDS
Diagonse by lipid profile in blood and indentification of mutations
Jamaican Vomiting Sickness
From unripe ackee fruit, which contains inhibitor for short and medium chain acyl-CoA-dehydrogenase
Carnitine Palmitoyl Transferase II deficiency
unable to take of carnitine to add acetyl Co A
elevated fatty acids in blood, and elevated acylcarnitine
autosomal recessive, muscle pain and weakness and myglobinuria after prolonged exercise
How and why does 2,3 bisphosphoglycerate divert from glycolysis?
2,3 BPG in RBC regulates oxygen delievery
It displaces oxygen from hemoglobin and stabilizes deoxyhemoglobin
Lack of O2 halts ETC, backs up glycolysis, increases [3-phophoglycerate]
3-phosphoglycerate then gets converted to 2,3 BPG which increases oxygen delivery to tissues
What are ketone bodies?
Body's normal response to starvation
Decreased insulin/glucgon ratio stimulates hormone sensitive lipase to free fatty acids
FA cannot cross blood-brain barrier, liver responds by cleaving glycogen , when thats depleated coverts to ketone synthesis.
Describe the process of ketone synthesis
Increased levels of B-oxidation in liver result in lots of NADH + H and acetyl CoA
This drives TCA backwards, oxaloacetate is converted to malate, malate leaves TCA for gluconeogenesis
Less oxaloacetate diverts acetyl CoA to ketone body synthesis, acetone is byproduct and is exhaled
Excessive ketone production leads to ketoacidosis (drop in blood pH)
*In hypoglycemic patient, abscence of elelvated ketone bodies suggests defect in fatty acid metabolism such as MCAD*
Describe the significance of special cases of fatty acid catabolism: the breakdown of odd chain length and branched chain fatty acids, oxidation of unsaturated fatty acids, and peroxisomal oxidation
Unsaturated fatty acids- get less energy, loose a little energy for each point of unsaturation
Odd chain fatty acids- left with 3 carbon fatty acid (Propionyl CoA which can enter TCA at 6 oclock
Long chain fatty acids- (more that 22 carbons) degraded in peroxisomes. Similar process but transfers electrons to molecular oxygen and then creates peroxide all the way down to short chain and then transferred to mitochondria
Branched Chain Fatty acids- humans can’t make but plants can, makes cuts to get acetyl CoA and propinal CoA
What does pyruvate dehydrogenase do?
Links glycolysis and TCA cycle
What are the functions of the TCA cycle?
1. Oxidize 2 Carbons from acetate to CO2
2. Reduce NADH and FADH2, generate GTP
3. Generate precursors for biosynthesis