fatty acid oxidation Flashcards
- Explain why fatty acids are a major/preferred fuel source for liver, heart and muscle (but not the brain) at all times, and the major energy source for all tissues under starvation conditions.
Fatty acids are more reduced than proteins or carbs so more energy is extracted with oxidation. Also, they are hydrophobic so they are not hydrated as much. Fatty acids are not used in the brain b/c they cant cross the BBB.
- List the three stages of fatty acid oxidation.
- release of Fatty acid from TAG. 2. Transport FA into mitochondrial matrix. 3. repeated cycles of oxidation
describe fatty acid release from triacylglycerol during starvation
Low insulin and high epi > epi activates adenylyl cyclase > cAMP > cAMP activates protein kinase > phosphorylates hormone-sensitive lipase and activates it > lipase releases fatty acids from triacylglycerol
describe transport of long chain FA into mitochondrial matrix
FA converted to Fatty acyl CoA in cytosol> cross outer mitochondrial membrane >FA group transferred to carnitine via carnitine palmitoyl transferase 1 (rate limiting step in beta oxidation) > crosses inner mitochondrial membrane via translocase > converted back to fatty acyl CoA in matrix via carnitine palmitoyl-transferase II
describe transport of short or medium chain FA into mitochondria
Can diffuse into matrix without carnitine
inhibitor of carnitine palmitoyl-transferase I
malonyl CoA- intermediate in fatty acid synthesis
deficiency in carnitine production
can cause muscle cramping, weakness b/c oxidation of long chain fatty acids is primary source of energy. Liver shows massive amounts of triacylglycerol deposits
Products of Beta oxidation
1 Acetyl CoA, 1 FADH2, and 1 NADH
List the steps in beta oxidation
Fatty acyl CoA > enoyl CoA + FADH2 (Acyl CoA dehydrogenase) > 3-hydroxyacyl CoA (enoyl CoA hydratase) > 3-ketoacyl CoA (beta-hydroxy-CoA dehydrogenase) + NADH > release of acetyl CoA then transfer fatty acyl CoA which is 2 carbons shorter for another round of oxidation (thiolase)
forms of Acyl CoA dehydrogenase
Four forms of the enzyme exist specific for short (4-8), medium (4-14) and long (12-18) and very long carbon chains
how many ATP are formed by beta oxidation of palmityl CoA
131 ATP from 16 carbonds
describe oxidation of fatty acid with odd-number of carbons
Last round leaves fatty acyl CoA with 3 carbons > D-methylmalonyl CoA (propionyl CoA carboxylase adds carboxyl) > L-methylmalonyl CoA > succinyl CoA > enters TCA cycle
when does peroxisomal beta oxidation occur
Major site of beta oxidation for very long chain and branched fatty acids.
what is alpha oxidation
Phytanic acid is a branched chain fatty acid that is not a substrate for Acyl CoA dehydrogenase so it is hydroxylated at the a-carbon by fatty acid a-hydroxylase, then decarboxylated and activated to its CoA derivative for b-oxidation.
- Explain how fatty acid breakdown and synthesis are coordinately regulated, and connected to carbohydrate metabolism.
When insulin is high it activates protein phosphatase which activates acetyl CoA carboxylase (promotes fatty acid synthesis) and inhibits hormone-sensitive lipase (inhibits release of FA from fat stores). When glucagon is high, it activates protein kinase which activates hormone sensitive lipase (promotes FA release from stores) and inactivates Acetyl CoA carboxylase (inhibits fatty acid synthesis)
- To learn what ketone bodies are
Ketone bodies are produced in liver from excess acetyl CoA . Serve as substrates for oxidative metabolism when glucose is low
synthesis of ketone bodies
Fatty Acyl CoA+ acetyl CoA (thiolase) > actetoacetyl CoA > HMG CoA (HMG CoA synthase- rate limiting) > acetoacetate (HMG CoA lyase) > 3-hydroxybutyrate or acetone
list the names of ketone bodies
acetoacetate, 3-hydroxybutyrate and acetone are collectively called ketone bodies
Which organs use ketones as primary fuel choice
cardiac muscle and renal cortex
When are high levels of ketone bodies produced
During extreme metabolic stress or starvation- if rate of formation is higher than rate of use, levels rise in the blood (ketonemia) and eventually in urine (ketonuria)
- To explain why type I diabetes patients often have high levels of keton bodies.
When type 1 diabetics fail to take insulin Hormone sensitive lipase is activated, releasing large amounts of fatty acids from adipose. Fatty acid oxidation produces high levels of NADH which inhibits TCA cycle and forces excess acetyl CoA down ketone pathway.
symptoms of diabetic ketoacidosis
acetoacetate and 3-hydroxybutrate are strong acids, so blood pH is decreased and metabolic acidosis occurs. Acetone is volatile so it can be smelled on the breathe
