Fatty Acid Oxidation Flashcards
TAG to FA key regulatory step controlled by what?
Hormone sensitive lipases
Where does B-oxidation take place?
Mostly cytosol
What catalyzes acetyl CoA to carnitine? Why is this important? What inhibits this?
- CPT 1 or 2
- Important because it is how the acetyl CoA to the mitochondria
- malonyl CoA inhibits this
Why is it called beta-oxidation?
Oxidation occurs on the beta carbon
What are the products of FA oxidation?
FADH2 and NADH, which go through the ETC
Peroxisomal FA oxidation
- Usually for branched or very long chain fatty acids
- Processed to medium chain, then join into the mitochondria for further breakdown
What happens to odd number (propionyl-CoA)?
Becomes succinyl CoA and joins the TCA cycle
When is HSL activated?
When phosphorylated by a cAMP-dependent protein kinase
- in the presence of high levels of insulin and glucose, HSL is dephosphorylated and is inactive
What is the fate of glycerol during FA oxidation?
Liver is the only tissue with glycerol kinase, and so it can convert glycerol —> Glyceraldehyde 3 Phospate which can enter glycolysis or gluconeogenesis
___ is the RLS in beta-oxidation. It is allosterically inhibited by _____
- CAT 1
2. malonyl CoA
Manifestations of deficiency of carnitine
- TAG deposits in liver
2. Muscle cramping, hypoglycemia, weakness or death
Acyl CoA Dehydrogenases
- In the mitochondrial matrix
- Oxidize acyl CoAs
- Four forms (short, medium, long, and very long)
- Use FAD and introduce a trans double bond
Deficiencies result in severe hypoglycemia and may be a significant cause of SIDS (because relies on milk which has medium length FA)
Enoyl CoA Hydratase
Adds water across the trans double bond created in
Beta-hydroxy-CoA Dehydrogenase
Oxidizes the hydroxyl generating B-keto acyl-CoA and NADH from NAD
Thiolase
Releases acetyl CoA and transfers the FA shortened by two carbons to CoA-SH for another round of B-oxidation
Disorders of peroxisomal B-oxidation
Zwelleger syndrome and X-linked adrenoleukodystrophy
Alpha-oxidation of fatty acids
- phytanic acid, a branched chain fatty acid
- hydroxylated at the alpha-carbon by fatty acid a-hydroxylase, then decarboxylated and activated to its CoA derivative for B-oxidation
Deficiency of alpha-hydroxylase causes Refsum disease
Acyl CoA Dehydrogenase Deficiency
- Medium chain is most common
- Related to SIDS
- Hypoglycemia, sleepiness, vomiting, coma
- Treated with low fat, high carb diet
Refsum Disease
- Accumulation of large amounts of phytanic acid
- pigmented retina and polyneuropathy
- Onset before age 20
- neurologic
Peroxisomal Biogenesis Disorders
- Juvenile onset of a constellation of symptoms
- Fatal before age 2
- Ether linked glycerol lipids are also defective
What happens to acetyl CoA when it is in excess?
Converted to ketone bodies and exported from the liver (because the TCA cycle becomes inhibited)
Ketone bodies are: Acetoacetate; acetone; 3-Hydroxybutyrate
Ketone bodies
- Produced in liver from excess acetyl CoA
- Exported to the brain when fuel is not available
- Substrates for oxidative metabolism when glucose is low
- High levels of NADH during FA oxidation promotes conversion of acetoacetate into 3-hydroxybutyrate (else acetone is formed)
Ketoacidosis
Abnormal rise in concentration of ketone bodies in blood, lowering pH, such as in starvation and low carb diets
DM1: lack of insulin activates HSL –> FA oxidation –> increased acetyl CoA –> slowing of TCA cycle and increased NADH –> ketone body synthesis
1g fat = __ energy
1g sugar = __ energy
fat = 9kcal sugar = 4kcal
CPT 1 deficiency leads to lowered ___ compared to normal?
Glucose and Ketone bodies
- Cannot transport between mitochondria and cytosol
- Cannot use as energy
