fatty acid oxidation

Question 1

1. 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.

Answer 1

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.

Question 2

2. List the three stages of fatty acid oxidation.

Answer 2

1. release of Fatty acid from TAG. 2. Transport FA into mitochondrial matrix. 3. repeated cycles of oxidation

Question 3

describe fatty acid release from triacylglycerol during starvation

Answer 3

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

Question 4

describe transport of long chain FA into mitochondrial matrix

Answer 4

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

Question 5

describe transport of short or medium chain FA into mitochondria

Answer 5

Can diffuse into matrix without carnitine

Question 6

inhibitor of carnitine palmitoyl-transferase I

Answer 6

malonyl CoA- intermediate in fatty acid synthesis

Question 7

deficiency in carnitine production

Answer 7

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

Question 8

Products of Beta oxidation

Answer 8

1 Acetyl CoA, 1 FADH2, and 1 NADH

Question 9

List the steps in beta oxidation

Answer 9

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)

Question 10

forms of Acyl CoA dehydrogenase

Answer 10

Four forms of the enzyme exist specific for short (4-8), medium (4-14) and long (12-18) and very long carbon chains

Question 11

how many ATP are formed by beta oxidation of palmityl CoA

Answer 11

131 ATP from 16 carbonds

Question 12

describe oxidation of fatty acid with odd-number of carbons

Answer 12

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

Question 13

when does peroxisomal beta oxidation occur

Answer 13

Major site of beta oxidation for very long chain and branched fatty acids.

Question 14

what is alpha oxidation

Answer 14

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.

Question 15

3. Explain how fatty acid breakdown and synthesis are coordinately regulated, and connected to carbohydrate metabolism.

Answer 15

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)

Question 16

4. To learn what ketone bodies are

Answer 16

Ketone bodies are produced in liver from excess acetyl CoA . Serve as substrates for oxidative metabolism when glucose is low

Question 17

synthesis of ketone bodies

Answer 17

Fatty Acyl CoA+ acetyl CoA (thiolase) > actetoacetyl CoA > HMG CoA (HMG CoA synthase- rate limiting) > acetoacetate (HMG CoA lyase) > 3-hydroxybutyrate or acetone

Question 18

list the names of ketone bodies

Answer 18

acetoacetate, 3-hydroxybutyrate and acetone are collectively called ketone bodies

Question 19

Which organs use ketones as primary fuel choice

Answer 19

cardiac muscle and renal cortex

Question 20

When are high levels of ketone bodies produced

Answer 20

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)

Question 21

5. To explain why type I diabetes patients often have high levels of keton bodies.

Answer 21

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.

Question 22

symptoms of diabetic ketoacidosis

Answer 22

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