FORM & FUNCTION (Fat breakdown,beta-oxidation) Flashcards
Metabolic fuel:
-when cells need energy, fatty acid is utilized
Simple steps to getting energy from fat:
- Breakdown of triglycerides into FFA
- Transport of FFA to destination tissue
- Activation of FFA into fatty acyl-CoA
- Processing of acetyl-CoA (beta-oxidation) for entry into the TCA cycle
Step 1: Triglyceride breakdown (lipolysis), SIGNALS
Signal: hormones
-catecholamines (E, NE)
-glucocorticoids (cortisol)
-thyroid hormones (T3,T4)
Step 1: Triglyceride breakdown (lipolysis)
- Hormones bind to beta-receptor
- Adenylate cyclase is activated (ATP to cAMP)
- cAMP activates protein kinsase A
- PKA adds P to hormone sensitive lipase (activated)
- Hormone sensitive lipase breaks down triglycerides back to FFAs and glycerol
Once triglycerides are broken down by hormone sensitive lipase:
-FFA transported out of the cell and bind to albumin (taxi)
FFA+albumin:
-liver (re-packaging)
-destination tissue (beta-oxidation)
Fate of released FFA:
-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
Liver’s important role:
-in maintaining continuous cycling and redistribution of FA during lipolysis
Excess liver FA:
-steatosis (fatty liver)
-a problem in starvation or diabetic patients
Fate of glycerol:
-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)
Insulin (inhibitory) control of lipolysis:
-activates protein phosphate 1: removes P from hormone sensitive lipase (inactive)
-activate phosphodiesterase: converts cAMP to 5’AMP
-inhibits glucocorticoid
Glucocorticoid:
-active: increases total levels of hormone sensitive lipase
>biosynthesis
Fatty acid activation:
*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
Acyl-CoA synthetase:
-adds Acyl-CoA to FFA to put them in active form for beta-oxidation
Carnitine:
-attaches to FA-Acyl-CoA to transport it via carnitine transporter into the mitochondrial matrix
Carnitine palmitoyltransferase:
-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
Beta-oxidation overview:
-sequentially cleaves the FA
>2 carbons at a time to yield Acetyl-CoA molecules that enters the TCA cycle
Beta-oxidation steps:
-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)
Total ATP per fat molecule: (Palmitate molecule)
-7x beta-oxidations step: 7NADH (21ATP), 7FADH2(14ATP)
-8 acetyl-CoA entering TCA+ETC: 8GTP, 24 NADH (72ATP), 8FADH2 (16ATP)
TOTAL=131ATP
Comparison of ATP per carbon:
Fat=8.19
CHO aerobic=6.33
CHO anaerobic=0.33
Beta oxidation aerobic only:
-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
Advantage of fat:
-high energy content
*max ATP per carbon
Disadvantages to fat:
-cannot be used anaerobically
-cannot be used by the brain & RBC
