Lecture 6 Flashcards
(19 cards)
About fat
Types
1. Fatty acids - the “oxidizable” form of fat
2. Triglycerides - glycerol (also “oxidizable) + 3 fatty acid groups; stored in fat cells
3. Phospholipids - make up membranes (hydrophobic “head”, hydrophilic “tail”)
4. Sterols - cholesterol (in lipoprotein complexes); transporters
Storage
1. Adipose tissue (as triglycerides)
2. Muscle (intramuscular triglycerides)
Transport (poly soluble)
1. In blood as: triglycerides, lipoproteins; free fatty acids (attached to albumin)
2. Across sarcolemma (blood to Sarcoplasm): fatty acids translocase
3. Into mitochondria: carnitine transport system
Breakdown
1. Lipolysis - breakdown (hydrolysis) of triglyceride into its components
2. Oxidation - of fatty acids and glycerol
Fat sources during exercise
Adipose tissue - triglyceride (TG)
Blood - fatty acid
Muscle - intramuscular TG —> fatty acid
Lipolysis
Before fatty acids can be oxidized in the mitochondria, they must first be released from triglycerides and then activated, forming fatty acrylic CoA
Step 1: hydrolysis of triglycerides, rxn catalyzed by hormone sensitive lipase as follows:
Triglyceride + H2O —(HSL)—> 3 fatty acid + glycerol
Step 2: degradation of FA, rxn catalyzed by acrylic-CoA synthétase as follows:
Fatty acid + ATP + CoA (2P are split from ATP= 2 ATP for simplicity) –(ACS)—> fatty acyl CoA + AMP (Adenosine monophosphate) + PPi
Lipolysis
Albumin (fatty acid) - produce AMP - fatty acyl CoA (oxidized from a fatty acid)
Triglyceride - 1 glycerol + 3 fatty acids - produce AMP - then fatty acyl CoA (oxidized from a fatty acid)
Transport of Fatty Acyl-CoA
- fatty acyl-CoA must be transported across inner mitochondrial matrix because it is impermeable to CoA and its derivatives
- transport occurs using proteins and the small molecule carnitine
- FA attached to carnitine area able to cross the inner membrane through the protein transporter carnitine acylcarnitine translocase
Transport of fatty acyl-CoA - transport is carnitine
Acyl CoA = fatty acyl
CoACoASH = CoA
Transport of fatty acyl-CoA process
Fatty acyl CoA - carnitine - CoA - CPT2 - fatty acyl CoA
Beta oxidation
4 steps - Remove 1 acyl CoA, at each step
- initial process of oxidation of fatty acids
- four-step process that removes acetyl-CoA units, one at a time from fatty acyl CoA
- ultimately removes 2 carbons from fatty acyl-CoA producing 1 acetyl CoA, 1 NADH and 1 FADH2 (1 AMP)
- fatty acyl-CoA (less two carbons) then re-enters the process
- process is repeated until the original fatty acid is completely broken down to acetyl CoA groups
- ex. An 18-carbon fatty acid (oleoic acid) will go through 8 cycles of beta oxidation and yield 9 acetyl-CoA (18/2=9)
- 9 circles and 8 lines. O/O/O/O/O/O/O/O/O
Acyl CoA - also depending on how many carbons are attached
Enola CoA hydratase - (butter or margarine)
Beta oxidation process
Fatty acyl CoA - produce FADH2 and NADH, then the major production is acetyl-CoA
Processes added together
The beta oxidation produces acetyl-CoA which then gets added to the TCA-ETC
Fatty acid and glycerol breakdown
- each triglyceride molecule contains 3 fatty acid molecules
- assuming each is comprised of 18-carbon fatty acid (oleic acid), oxidation of oleic acid yields:
- 8 NADH + 8 FADH + 9 acetyl-CoA in 8 cycles of beta oxidation
- each acetyl-CoA yields 3 NADH + 1 FADH2 + 1 ATP in TCA cycle
- total per fatty acid
- NADH: 8 + (3x9) = 35 x 2.5 ATP/NADH = 87.5 ATP
- FADH2: 8 + (1x9) = 17 x 1.5 ATP/FADH2 = 25.5 ATP
- ATP: 1 x 9 = 9 ATP
- BUT 2 ATP needed to activate fatty acid in acyl CoA synthétase rxn = -2 ATP - therefore net ATP: 87.5 + 25.5 + 9 - 2 = 120 ATP
- 360 ATP molecules are produced from the oxidation of 3 fatty acid components (3 x 120 ATP)
- 17 ATP molecules form during glycerol breakdown to generate 377 ATP molecules for each triglyceride
Source - pathway - ATP yield per molecule neutral fat
1 molecule glycerol - glycolysis + citric acid cycle - 17
3 molecules of 18-carbon fatty acid - beta oxidation + citric acid cycle - 360
Total 377 ATP
Source of Acetyl-CoA for TCA cycle
With oxygen
Faster production of ATP but finite (less) ATP formation
- glucose (C6H12O6)
- glycolysis
- pyruvate
- acetyl-CoA
- TCA cycle
C6H12O6 + 6O2 + 32 (ADP + Pi) —> 6CO2 + 32 ATP + 6H2O
Slower production of ATP but infinite (unlimited) ATP formation
- fatty acid chain (C12H32O2)
- fatty acyl-CoA
- beta oxidation
- acetyl-CoA
- TCA cycle
- considerable energy yield compared to 32 net ATPs formed from glucose
C16H32O2 + 106 (ADP + Pi) —> 16 CO2 + 106 ATP + 16 H2O
Power vs Capacity
Obviously the energy “provider” must change with exercise intensity!
- required rate of ATP generation determines intensity
Maximal rate of ATP generation
- PCr highest
- glycolysis moderate
- CHO oxidation low
- fat oxidation very low
Maximal available energy
- PCr extremely low
- Glycolysis very low
- CHO oxidation moderate
- ft oxidation extremely high (not limited)
Substrate use during exercise
Lower ATP resynthesis rate —(intensity increasing)—> higher ATP resynthesis rate
Substrate utilization and exercise intensity
At rest fat is high and CHO is low
At 100 fat is low and CHO is high
The crossover point is at about 60% maximal oxygen uptake, and % energy derived at about 50%
Progressive effect of endurance training on metabolic adaptations in working skeletal muscle
Seven males; 2 hours of cycling @ 59%VO2max; 5-6x/week; for 4 weeks
Muscle biopsies were taken during cycling at baseline, 15 and 90 min on days 0,5, and 31
Training effects on glycogen
All the same PO and, thus, ATP resynthesis rate
Loss lots - 340 to 60
Increase storage 340 to 430
Lots reserved 430 to 340 (decrease depletion in glycogen “sparing”)
Training effects on intramuscular triglycerides
For the same work rate (i.e. ATP resynthesis requirement), there is a greater contribution of fat oxidation compared to carbohydrate oxidation
Reserved more
Increase storage
Loss lots (increase depletion of IMTG utilization)
fates of lactate
- majority of lactate produced in skeletal muscle cells will enter the blood stream
- lactate contains lots of potential energy
- it can be transported and taken up by other tissues and converted back to pyruvate:
1. Used as substrate to resynthesize ATP (skeletal muscle and other tissues)
2. Converted back to glucose and stored as glycogen
2 pyruvate + 2 NADH + 2 H+ <—(Lactate Dehydrogenase)—> 2 lactate + 2NAD+
- demonstrates pyruvate production
- keeps NADH and 2 H+ as NAD+ substrate
Lactate processes
Pyruvate <—(LDH)—> lactate - produces NAD+
Then lactate uses MCT to produce lactate in the capillary
