Review PCrReview PCr

Review GlycolysisReview Glycolysis

Review TCAReview TCA

HSL must stimulate the HSL must stimulate the catabolism of triglyceride catabolism of triglyceride

(glycerol + 3 FAs)(glycerol + 3 FAs) insulin (-)insulin (-) lactate (-)lactate (-) epi (+)epi (+) norepi (+)norepi (+) glucagon (+)glucagon (+) GH (+)GH (+) cortisol (+)cortisol (+)

If in adipose: glycerol may If in adipose: glycerol may enter circulation, be taken up enter circulation, be taken up by liver and phosphorylated to by liver and phosphorylated to

glycerol 3-phosphate glycerol 3-phosphate make new TGsmake new TGs enter the glycolytic pathwayenter the glycolytic pathway gluconeogenic precursor (via gluconeogenic precursor (via

dihydroxyacetone phosphate, DHAP)dihydroxyacetone phosphate, DHAP)

FAs can enter the muscle cell FAs can enter the muscle cell for further catabolizationfor further catabolization

Entry into cell no problem; Entry into cell no problem; entry into mitochondria for entry into mitochondria for Beta oxidation is similar to Beta oxidation is similar to

facilitated diffusion of glucose: facilitated diffusion of glucose: it takes othersit takes others

FAs are converted to a CoA FAs are converted to a CoA derivative by fatty acyl CoA derivative by fatty acyl CoA

synthasesynthase

Palmitate: 16C FA:Palmitate: 16C FA:

Palmitate Palmitate →→ palmitoyl CoA via long chain palmitoyl CoA via long chain acyl CoA synthaseacyl CoA synthase

ATP in and AMP out; net cost?ATP in and AMP out; net cost? now ready for beta oxidationnow ready for beta oxidation

Fatty acyl CoA must be Fatty acyl CoA must be transported across the mito. transported across the mito.

membrane and into the matrix membrane and into the matrix via carnitine shuttlevia carnitine shuttle

notice the “drop off” of CoA to combine with notice the “drop off” of CoA to combine with another fatty acyl CoAanother fatty acyl CoA

why supplement carnitinewhy supplement carnitine– increased carnitine, shuttle in more fat, more fat increased carnitine, shuttle in more fat, more fat

catabolism, even at restcatabolism, even at rest– partly b/c exercise causes an increased partly b/c exercise causes an increased

excretion of carnitine in urine, maybe lowering excretion of carnitine in urine, maybe lowering muscle levelsmuscle levels

no studies support this contention, need no studies support this contention, need mitochondria for carnitine to helpmitochondria for carnitine to help

NOW, beta oxidationNOW, beta oxidation

think of it as a merry-go round, dropping off think of it as a merry-go round, dropping off 2 carbons (acetyl CoA)2 carbons (acetyl CoA)

Two purposes of Beta OxidationTwo purposes of Beta Oxidation

cleave carbon atoms in pairs (acetyl CoA), cleave carbon atoms in pairs (acetyl CoA), degrading the FAdegrading the FA

produce high energy reducing equivalents, produce high energy reducing equivalents, NADH +H and FADHNADH +H and FADH22

Process of Beta oxidationProcess of Beta oxidation

most fats are 16 or 18 carbonsmost fats are 16 or 18 carbons

16C Palmitate:16C Palmitate:

5 ATP/ spin (n/2 - 1)5 ATP/ spin (n/2 - 1) 12 ATP/acetyl CoA (n/2)12 ATP/acetyl CoA (n/2) 7 spins X 5 = 35 ATP7 spins X 5 = 35 ATP 8 acetyl CoA X 12 = 96 ATP8 acetyl CoA X 12 = 96 ATP 35 + 96 = 131 ATP 35 + 96 = 131 ATP 2 ATP for activation, 131 - 2 = 129 ATP2 ATP for activation, 131 - 2 = 129 ATP

Uneven FAsUneven FAs

cleaving of pairs continues until last time, 2 cleaving of pairs continues until last time, 2 C and a 3CC and a 3C

3C fatty acid is propionyl CoA3C fatty acid is propionyl CoA propionyl CoA is converted to succinyl CoApropionyl CoA is converted to succinyl CoA

Glycerol catabolism: 19 ATPGlycerol catabolism: 19 ATP

Entire TGEntire TG

129 X 3 (3 FAs) = 387129 X 3 (3 FAs) = 387 387 + 19 (glycerol) = 406 ATP387 + 19 (glycerol) = 406 ATP

Acetyl CoA from Beta Acetyl CoA from Beta Oxidation must interact with Oxidation must interact with OXA to feed the TCA (CHO OXA to feed the TCA (CHO

flame)flame)

Acetyl CoA may be converted Acetyl CoA may be converted to ketones when not enough to ketones when not enough OXA (fasting, diabetes, and OXA (fasting, diabetes, and

prolonged exercise)prolonged exercise)

Ketones (or ketone bodies)Ketones (or ketone bodies)

two acetyl CoA condense to acetoacetatetwo acetyl CoA condense to acetoacetate acetoacetate reduced to 3-hydroxybutyrate acetoacetate reduced to 3-hydroxybutyrate

(if NADH:NAD ratio is high in mitochondria)(if NADH:NAD ratio is high in mitochondria) or, acetoacetate spontaneously, slowly or, acetoacetate spontaneously, slowly

undergoes a decarboxylation to acetoneundergoes a decarboxylation to acetone

this occurs in liverthis occurs in liver ketones may be used for energy, especially ketones may be used for energy, especially

by heart and kidneysby heart and kidneys

Fat catabolism during low Fat catabolism during low intensity exerciseintensity exercise

low intensity: 5 kcal/minlow intensity: 5 kcal/min

most (72%) derived from fatmost (72%) derived from fat 3.6 kcal from fat, 0.4 gms of fat3.6 kcal from fat, 0.4 gms of fat

double intensity: 10 kcal/mindouble intensity: 10 kcal/min

45% of energy is derived from fat45% of energy is derived from fat 4.5 kcal/min, 0.5 gm of fat4.5 kcal/min, 0.5 gm of fat

e.g., 5 kcal/min for 60 min = (5 e.g., 5 kcal/min for 60 min = (5 X 60) = 300 kcals, 24 gm fatX 60) = 300 kcals, 24 gm fat

10 kcal/min for 45 min = 450 10 kcal/min for 45 min = 450 kcals, 22.5 gm fatkcals, 22.5 gm fat

Therefore, should you Therefore, should you encourage some one to encourage some one to

exercise at low intensity to exercise at low intensity to “burn more fat”?????“burn more fat”?????

Fat facts:Fat facts:

fat utilization decreases when exercise fat utilization decreases when exercise follows a high CHO meal (increase in follows a high CHO meal (increase in circulating insulin)circulating insulin)

fat utilization decreases when lactate begins fat utilization decreases when lactate begins to accumulateto accumulate

ability to use fat as a fuel increases with ability to use fat as a fuel increases with trainingtraining