BC 34 Liver Metabolism Fasting Flashcards
Lipolysis location and process
Adipose tissue only
-to mobilize fat storage in fasting state
RL: hormone sensitive lipase (HSL)
process: TAG–> FFA and DAG
other lipases: DAG –> 2FFA and Glycerol
-typically lipolysis liberates twice as many FA as needed
-out of cell to albumin
NO FA OT BRAIN
FFA are major feul for tussues with mitochondria (except brain) in fasting state
FA Oxidation location and process
Liver and Tissues with Mito
Mitochondrial Matrix
-brain cells have mito but cannot ox exogenous FA bc cannot cross BB barrier
-supplies maj of energy dyring fasting
Process: FFA to AcCoA and NADH and FADH2
-accoA to TCA or Ketogenesis
-nadh and FADH2 to TCA and ETC
RL: Carnatine Shuttle: CPT1
Ketogenesis
LIVER ONLY
-mito matrix
Convert hydrophobic FA to hydrophilic ketone bodies for EXPORT only
-converted back to acCoA in brain, muscle and fetus
RL: HMG CoA Synthase
products: acetoacetate and B hydroxybutyrate (and acetone but cannot be used)
Hormone sensitive lipase
Regulated by IG and epinephrine via phosphorylation
epi–> phosphorylated HSL –>Gs-cAMP-PKA = phosphorylation and activation
insulin–>RTK= dephosphorylation/deactivation
Fasting state on HSL and clin correlations
increase epi decrease insulin = ACTIVATION
-inability to inhibit HSL
- despite regulation lipolysis still liberates 2x the amount of FA needed
- excess FA repackaged into TAG for liver, tehn converted to VLDL and return to adipose and muscle
Poorly Regulated Type I DiabetesL HSL exclusively active (decreased insulin levels) excess lipolysis
NiacinL inhibits lipolysis to reduce hypertriglyceridemiaL decreased prod of VLDL and LDL
????
FFA transport beginning from adipose tissue
LIPOLYSIS–> FA carried by serum albumin to tissues for oxidation
- FA uptake by muscle/liver mediated by MEMBRANE FA CARRIER PROT
- once inside FA “activated in cytosol (FATTY ACYL COA SYNTHETASE OR THIOKINASE) by attaching CoA to form fatty acyl co A (only form that can be metabolized)
Rate limiting step of FA Boxidation
Carnatine shuttle: getting it into the mitochondira
-cannot get in with CoA attached, can go in OMM but not IMM
-CPT1 (Carnitine Palmotoyl Transferase 1) RATE LIMITING ENZYME IN IMM removes CoA allowing translocase to carry it in
(other steps involved but this is RL enzyme)
-more AcCOA attached in matrix (made from Vit B5)
Malonyl CoA
Allosteric inhibitor of CPT1 in FED state
-produced during deNOVO FA synthesis by acetyl coA carboxylase
this is a regulation protection to ensure that newly synthesized FA are not immediately sent iinto mito and degraded.
B Ox of Saturated FA and product fates
On the B carbon of the FA (?)
-series of four reactions resulting in shortening of the FA cahin by TWO carbons generating three products- FADH2, NADH, Acetyl CoA
Acetyl CoA can either go towards TCA for more EST (SLOW in Fasting state) or Ketogenesis (most sent to ketone production)
TCA slow bc isocitrate dehydrogenase (RL of TCA) is inhibited by presence of NADH and ATP from Complex V
Ketogenesis
bhydroxybutyrate and acetoacetate and acetone (not metabolized)
RL: HMG CoA Synthase in Mito
effects on other pathways of increasing B ox
increased Ketogenesis
increased gluconeogenesis
decrease in TA cycle
- OAA sent to pyruvate carboxylase for fluconeogenesis
- muscle breakdown makes pyruvate, made to OAA
Keton Body Oxidation location and process
Ketone bodies–> to acetyl co A
(bhydroxybutyrate and acetoacetate)
MUSCLE BRAIN (not liver)
2 ketone bodies exported out of liver and transfer to bklood to peripheral tissues of brain and muscle
ketones converted BACK to Acetyl COA tehn TCA
LIVER CANNOT OXIDIZE KETONE BODIES
Protien sparing effects in different metabolic states
Fed: dietary carbs
fasting: liver glycogen
long fast: ketone bodies
Ketone body production in extreme fasting
even higher than fasting (also uncontrollable type I diebetics or with higher fat diets ie neonates with milk or adults with adkins)
when will ketone bodies appear in urine
20 hours after meal (skip break/lunch–> seen by mid afternoon)
decrease carb diet, decrease IC directs body to use fats as feuls, detogenesis is active and gluconeogenesis
brain- AA-glucose
