Lipolysis

Largest storage form of energy Provides energy at the slowest rate Stored: –adipose tissue –muscle –Brain, CNS, abdomen, etc. Use of lipids spares glycogen during prolonged work

Lipids Substance that is water insoluble, but soluble in organic solvents Most are Non- polar (uncharged) Important in a variety of roles

Cholesterol: Sterol: Comes from diet or is synthesized in liver Important: Cell membrane structure Steroid hormone synthesis Testosterone, Estrogen, Corticosteroids

Derived from incomplete Fat metabolism Formed from excess Acetyl-CoA Kreb’s cycle slows due to low CHO stores 2 Acetyl-CoA molecules Acetoacetyl-CoA Acetoacetate D-β-Hydroxybutyrate Last two used for energy

Exception to “polarity” rule Found in cellular membranes Profers some “selectivity” to the membrane

Triglycerides –Biggest percentage –Cholesterol and phospholipids –Digested in small intestine –Bile: emulsifying agent Fat digestion

Pancreatic lipase –Breaks down fat globule (Micelles) Monoglycerides, FFA and glycerol –Taken up by small intestinal cells –Repackaged with intestinal cells as Chylomicrons –Released into lymph Different from carbs, most go to heart first

Chylomicrons and lipoproteins Two mechanisms of fat clearance from blood –Transport to liver Uses fats for fuel Converts to lipoproteins –Mix of trigs, phospholipids, cholesterol and protein –Protein allows transport in blood

Lipoproteins Classified by density –VLDL: mostly triglycerides –LDL: mostly cholesterol –HDL: mostly protein

Uptake of fatty acids: Lipoprotein lipase In capillary/cell interface of most tissues –This enzyme facilitates uptake of FFA from blood after a meal Hormone sensitive lipase –Essentially same enzyme Breaks down intracellular lipids in fasted state

Lipid utilization during exercise Primarily used: –Rest, prolonged low-moderate intensity exercise, recovery from exercise Complicated –Multi-step Mobilization Circulation Uptake Activation –Fatty-acyl-CoA Translocation Β-oxidation Mitochondrial oxidation

Mobilization HSL –Breaks down stored triglycerides –Stimulated by catecholamines (rapid phase) –Growth hormone (prolonged phase) –Triglycerides carried in blood by albumin

Circulation and uptake FFA circulated in blood bound to albumin Uptake –Directly related to circulating concentration –Rate of blood flow Increased flow, increased delivery, increased uptake and utilization

Activation and translocation 1)FFA are taken up by FABP 2)FAT (fatty acid transporter) –Brings the FFA into the cell 3) Attachment of FA to CoA molecule –Fatty acyl-CoA –Outer mitochondrial membrane 4) Translocation –Into mitochondrial matrix –Carnitine and CAT1 and CAT

β-oxidation Breaks down FA-CoA to acetyl-CoA (2C fragment) Starts the process of fatty acid oxidation 16C FA requires: –7 cycles of β-oxidation –Each cycle produces 1 Acetyl-CoA, 1 NADH and 1 FADH 2 –So 16C FA produces how many ATP? –8 acetyl-CoA, 7 NADH, 7 FADH 2 –WHY 8 Acetyl-CoA? –Each acetyl-CoA = 12 ATP (3 NADH, 1 FADH, 1 ATP) –Activation costs 2 ATP (equivalent, one ATP to AMP)

Oxidation of fatty acids After β-oxidation –Acetyl-CoA Enters Kreb’s cycle –NADH and FADH go to electron transport chain

Free fatty acids: rest and exercise Opposite of CHOs –Fasted state raises FFA –Most pronounced during low-to- moderate intensity exercise

Intramuscular triglycerides Stored in muscle much like glycogen Hormone Sensitive Lipase –Breaks down trigs within cell –Hard to quantify utilization Concomitant use by cell and uptake from blood

Intramuscular lipolysis Perhaps used in type I fibers Results suggest that they are used primarily during recovery from exercise

Lipid oxidation in muscle FFA are taken up by the muscle –Training increases this ability Intramuscular TG –Probably used when glycogen becomes depleted –Most likely used in recovery –Used to a great extent by diving mammals

Tissue specific fat metabolism Heart and liver specially adapted to fat utilization Brain, RBCs use glucose almost exclusively Muscle: in between –Type IIb: use relatively little fat –Type I: use much more fat Muscle mitochondrial adaptations –Much greater than those associated with the cardio- circulatory system (i.e. heart, capillary vol., etc.) –Increases ability to use fat (particularly when glycogen is low) –Note how FFA are utilized much more quickly when enzyme content is doubled

Biggest factor in Fuel selection –Power output Rest –Mostly fat used Exercise –Depends on intensity Training –Can shift fat curve to left Sympathetic nervous system stimulation –Shifts fat curve right Crossover concept

Note that it is 50% fat-50% CHO at very low power output (~30% Vo 2 max) As power output rises, fat oxidation slows due to: –The complexity of the FA oxidation process –Reduced blood flow to inactive tissues –Sympathetic nervous system stimulation (which increases CHO utilization) –Endurance training only affects the percentages slightly

Glycerol –Marker of FFA mobilization from fat stores –This data suggest slightly greater mobilization after training at 45% FFA –Simultaneously mobilized into blood and taken up by the tissues –Why are blood levels of FFA lower after training?

Glycerol –Rate of appearance –Measure of mobilization –Note that mobilization is greater following training FFA –Appearance and disappearance Measure of turnover –Note that prior to training FFA turnover falls with intensity –After training Pattern is different

Ketosis: Fuel source? Under starvation conditions –When carbohydrate use is minimal –Reduces protein catabolism for energy needs –Ketone bodies Acetoacetate, β-hydroxybutyrate Acetone

Can be taken up by brain Converted to acetoacetate Converted to acetyl-CoA and oxidized Problems?