Fatty Acid Oxidation

Question 1

TAG to FA key regulatory step controlled by what?

Answer 1

Hormone sensitive lipases

Question 2

Where does B-oxidation take place?

Answer 2

Mostly cytosol

Question 3

What catalyzes acetyl CoA to carnitine? Why is this important? What inhibits this?

Answer 3

• CPT 1 or 2
• Important because it is how the acetyl CoA to the mitochondria
• malonyl CoA inhibits this

Question 4

Why is it called beta-oxidation?

Answer 4

Oxidation occurs on the beta carbon

Question 5

What are the products of FA oxidation?

Answer 5

FADH2 and NADH, which go through the ETC

Question 6

Peroxisomal FA oxidation

Answer 6

• Usually for branched or very long chain fatty acids

- Processed to medium chain, then join into the mitochondria for further breakdown

Question 7

What happens to odd number (propionyl-CoA)?

Answer 7

Becomes succinyl CoA and joins the TCA cycle

Question 8

When is HSL activated?

Answer 8

When phosphorylated by a cAMP-dependent protein kinase

• in the presence of high levels of insulin and glucose, HSL is dephosphorylated and is inactive

Question 9

What is the fate of glycerol during FA oxidation?

Answer 9

Liver is the only tissue with glycerol kinase, and so it can convert glycerol —> Glyceraldehyde 3 Phospate which can enter glycolysis or gluconeogenesis

Question 10

___ is the RLS in beta-oxidation. It is allosterically inhibited by _____

Answer 10

1. CAT 1

2. malonyl CoA

Question 11

Manifestations of deficiency of carnitine

Answer 11

1. TAG deposits in liver

2. Muscle cramping, hypoglycemia, weakness or death

Question 12

Acyl CoA Dehydrogenases

Answer 12

1. In the mitochondrial matrix
2. Oxidize acyl CoAs
3. Four forms (short, medium, long, and very long)
4. 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)

Question 13

Enoyl CoA Hydratase

Answer 13

Adds water across the trans double bond created in

Question 14

Beta-hydroxy-CoA Dehydrogenase

Answer 14

Oxidizes the hydroxyl generating B-keto acyl-CoA and NADH from NAD

Question 15

Thiolase

Answer 15

Releases acetyl CoA and transfers the FA shortened by two carbons to CoA-SH for another round of B-oxidation

Question 16

Disorders of peroxisomal B-oxidation

Answer 16

Zwelleger syndrome and X-linked adrenoleukodystrophy

Question 17

Alpha-oxidation of fatty acids

Answer 17

• 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

Question 18

Acyl CoA Dehydrogenase Deficiency

Answer 18

• Medium chain is most common
• Related to SIDS
• Hypoglycemia, sleepiness, vomiting, coma
• Treated with low fat, high carb diet

Question 19

Refsum Disease

Answer 19

• Accumulation of large amounts of phytanic acid
• pigmented retina and polyneuropathy
• Onset before age 20
• neurologic

Question 20

Peroxisomal Biogenesis Disorders

Answer 20

• Juvenile onset of a constellation of symptoms
• Fatal before age 2
• Ether linked glycerol lipids are also defective

Question 21

What happens to acetyl CoA when it is in excess?

Answer 21

Converted to ketone bodies and exported from the liver (because the TCA cycle becomes inhibited)

Ketone bodies are: Acetoacetate; acetone; 3-Hydroxybutyrate

Question 22

Ketone bodies

Answer 22

• 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)

Question 23

Ketoacidosis

Answer 23

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

Question 24

1g fat = __ energy

1g sugar = __ energy

Answer 24

fat = 9kcal
sugar = 4kcal

Question 25

CPT 1 deficiency leads to lowered ___ compared to normal?

Answer 25

Glucose and Ketone bodies

• Cannot transport between mitochondria and cytosol
• Cannot use as energy