FORM & FUNCTION (Fat breakdown,beta-oxidation)

Question 1

Metabolic fuel:

Answer 1

-when cells need energy, fatty acid is utilized

Question 2

Simple steps to getting energy from fat:

Answer 2

1. Breakdown of triglycerides into FFA
2. Transport of FFA to destination tissue
3. Activation of FFA into fatty acyl-CoA
4. Processing of acetyl-CoA (beta-oxidation) for entry into the TCA cycle

Question 3

Step 1: Triglyceride breakdown (lipolysis), SIGNALS

Answer 3

Signal: hormones
-catecholamines (E, NE)
-glucocorticoids (cortisol)
-thyroid hormones (T3,T4)

Question 4

Step 1: Triglyceride breakdown (lipolysis)

Answer 4

1. Hormones bind to beta-receptor
2. Adenylate cyclase is activated (ATP to cAMP)
3. cAMP activates protein kinsase A
4. PKA adds P to hormone sensitive lipase (activated)
5. Hormone sensitive lipase breaks down triglycerides back to FFAs and glycerol

Question 5

Once triglycerides are broken down by hormone sensitive lipase:

Answer 5

-FFA transported out of the cell and bind to albumin (taxi)

Question 6

FFA+albumin:

Answer 6

-liver (re-packaging)
-destination tissue (beta-oxidation)

Question 7

Fate of released FFA:

Answer 7

-the amount of FFA released is a lot more than the energy requirement
-excess FA are taken up by liver and repackaged into VLDL and directed to tissues again
>doesn’t normally accumulate in blood

Question 8

Liver’s important role:

Answer 8

-in maintaining continuous cycling and redistribution of FA during lipolysis

Question 9

Excess liver FA:

Answer 9

-steatosis (fatty liver)
-a problem in starvation or diabetic patients

Question 10

Fate of glycerol:

Answer 10

-as TG is broken down, glycerol molecules are transported to the liber that is then primarily used for gluconeogenesis
>it is soluble and enters bloodstream
*important step in starvation survival (glucose to feed brain or RBC)

Question 11

Insulin (inhibitory) control of lipolysis:

Answer 11

-activates protein phosphate 1: removes P from hormone sensitive lipase (inactive)
-activate phosphodiesterase: converts cAMP to 5’AMP
-inhibits glucocorticoid

Question 12

Glucocorticoid:

Answer 12

-active: increases total levels of hormone sensitive lipase
>biosynthesis

Question 13

Fatty acid activation:

Answer 13

*FA must enter mitochondria before beta-oxidation
-use CD63 to insert FFA into cytoplasm
-activated by first adding a co-enzyme group called Acyl-CoA to it
-use carnitine to bring FA-Acyl-CoA into mitochondrial matrix

Question 14

Acyl-CoA synthetase:

Answer 14

-adds Acyl-CoA to FFA to put them in active form for beta-oxidation

Question 15

Carnitine:

Answer 15

-attaches to FA-Acyl-CoA to transport it via carnitine transporter into the mitochondrial matrix

Question 16

Carnitine palmitoyltransferase:

Answer 16

-carnitine is released from FA-Acyl-CoA complex
-FA-Acyl-CoA complex can be used for beta oxidation
>converted to Acetyl-CoA
-carnitine goes back to cytoplasm

Question 17

Beta-oxidation overview:

Answer 17

-sequentially cleaves the FA
>2 carbons at a time to yield Acetyl-CoA molecules that enters the TCA cycle

Question 18

Beta-oxidation steps:

Answer 18

-4 step reaction to shorten to FFA, 2 C at a time to generate Acetyl-CoA
-produces 1 FADH2 and 1 NADH each round
*repeated 7 times to yield 8x Acetyl-CoA (ex. palmitoyl-CoA)

Question 19

Total ATP per fat molecule: (Palmitate molecule)

Answer 19

-7x beta-oxidations step: 7NADH (21ATP), 7FADH2(14ATP)
-8 acetyl-CoA entering TCA+ETC: 8GTP, 24 NADH (72ATP), 8FADH2 (16ATP)
TOTAL=131ATP

Question 20

Comparison of ATP per carbon:

Answer 20

Fat=8.19
CHO aerobic=6.33
CHO anaerobic=0.33

Question 21

Beta oxidation aerobic only:

Answer 21

-fat can only produce ATP aerobically
-does not directly produce ATP, but utilizes NADH/FADH2 that relies on oxygen on the ETC
-TCA cycle does not directly require oxygen, it requires the ETC to recycle NAD+ and FAD as cofactors

Question 22

Advantage of fat:

Answer 22

-high energy content
*max ATP per carbon

Question 23

Disadvantages to fat:

Answer 23

-cannot be used anaerobically
-cannot be used by the brain & RBC