Carbohydrate metabolism 1-3 (wk4)

Question 1

Describe what ATP (adeno triphosphate)

Answer 1

-1 ATP molecule is used per actin-myosin power stroke
-There are 100’s of myosin heads within each sarcomere
-There are 100’s of thousands sarcomeres within each muscle fibre
-There are approx 250,000 muscle fibres in the biceps brachii
-Assuming all fibres are engaged, a single twitch requires ~7.5 billion ATP molecules
-The demand for ATP hydrolysis during strenuous whole-body exercise can be as high as 12 hexillion molecules of ATP per minute or 1kg of ATP per minute

Question 2

How the ATP-ADP cycle relates to anabolism and catabolism
-ATP-ADP cycle

Answer 2

-ATP-ADP cycle -> ATP is a high energy nucleotide with three phosphate groups attached to a ribose sugar. The negative charge on the terminal oxygen of the phosphate group (PO4-) acts like a compressed spring, as it repels the rest of the molecule. Chemical energy is released from ATP when it’s hydrolysed, losing a phosphate group (∆G=-6.4Kcal/mol)

Question 3

How the ATP-ADP cycle relates to anabolism and catabolism
-Anabolic reactions

Answer 3

-Anabolic reactions -> Anabolic reactions (+∆G, endergonic) are coupled to the hydrolysis (catabolism) of ATP to ADP + Pi (inorganic phosphate) + energy (-∆G, exergonic) to perform cellular work.

Question 4

How the ATP-ADP cycle related to anabolism and catabolism
-Catabolic reactions

Answer 4

-Catabolic reactions -> Catabolic reactions (-∆G, exergonic) release energy which can be used for ATP synthesis. The net energy from ATP breakdown/synthesis is ‘manipulated’ by cells in order to allow both anabolic and catabolic reactions to proceed.

Question 5

Describe the turnover of ATP-ADP cycle during exercise

Answer 5

-ATP supplies the demand of energy from skeletal muscle and other tissues during exercise
-A human w/ energy expenditure of 2000kcal per day turns over ~ 45kg of ATP
-The demand for ATP hydrolysis during strenuous exercise can be as high as 1kg per minute
-The metabolic pathways used to resynthesize ATP vary for different types of exercise

Question 6

Describe the utilisation of ATP during exercise

Answer 6

1. Mechanical energy -> muscle contraction
2. Electrical energy -> electrical nerve impulses (Na+ - K+ pump and Ca2+ pump)

Question 7

Explain changes in skeletal muscle (ATP) during maximal exercise

Answer 7

-Stored ATP in muscle would last ~3 seconds during maximal exercise
-Muscle can keep on going through accumulating breakdown products of ATP -> ADP, AMP and PCr

Question 8

How myokinase can replenish ATP

Answer 8

-Myokinase adds phosphate groups
-Myokinase reaction is anaerobic and maintains ATP during hard exercise
-The reaction is favoured because of:
* Reduced ATP
* Increased ADP
* AMP is broken down into the liver and then excreted via the kidneys by adenylate deaminase (urea cycle) to favour more ATP formation

Question 9

Explain changes in skeletal muscle (PCr) during maximal exercise

Answer 9

-PCr has highest phosphoryl transfer potential
-Creatine kinase rapidly drives ATP synthesis during hard exercise
-PCr outweighs Cr in muscle (2:1) to favour the conversion to Cr and ATP
-Although PCr stores are 3-4 times larger than ATP, the resynthesis of PCr stores is slower than ATP
-PCr stores last ~7 seconds during maximal exercise
-CK maximal rate of ATP resynthesis is 2.6 mmol/kg/s

Question 10

Describe the enzymatic pathway converting Pcr to ATP

Answer 10

-Integration: ATP regeneration during exercise -> ATP is ~8mmol/kg, but the maximal demand during exercise is ~3mmol/kg/sec. ATP doesn’t drop below 60% of resting levels during exercise, due to the enzymes myokinase and creatine kinase.
-PCr provides the initial demand of ATP (~7 sec). Cr levels increase.
-Pi increases and ADP increases modestly because myokinase reutilised ADP to generate more ATP
-Beyond these anaerobic pathways, ATP is supplies through the breakdown of carbohydrates and fats – anaerobic and aerobic metabolism.

Question 11

How ATP is hydrolysed and resynthesized during maximal exercise

Answer 11

How ATP is hydrolysed and resynthesized during maximal exercise:
-Resynthesis of ATP is optimised for different activities by utilising different energy systems
-These vary in maximal rates and sustainability

Question 12

Describe and draw the relationship between the breakdown of glucose and Gibbs free energy

Answer 12

-Carbohydrates as a source of energy -> Glucose is rich in C-H bonds that can yield energy. The breakdown of glucose is associated with a negative change in Gibbs free energy (-∆G)

Question 13

Describe the basic process of carbohydrate digestion and absorption

Answer 13

-Digestion -> Carbohydrate digestion begins in the mouth (saliva) and then small intestine (pancreatic juices), where the enzyme (alpha)-amylase hydrolyses (alpha)(1-4)-glycosidic bonds in starch to short-chain carbohydrates (oligosaccharides). Oligosaccharides are then broken down into disaccharides in the villi of the small intestine.
-Specific enzymes such as lactase, maltase and sucrase then breakdown disaccharides to monosaccharides
-Absorption -> Monosaccharides are then absorbed into cytosol of enterocytes and transported into capillaries that empty into venous blood and the portal vein that supplies the liver

Question 14

Key steps regulating glycogen synthesis and breakdown
-Glycogen content of liver and muscle

Answer 14

-Glycogen content of liver and muscle -> Glycogen is mainly stored in the liver (3-7%) and muscle (1-1.5%). A lean female weighing 62kg will have approximately 233g of muscle glycogen and 70g of lover glycogen. In muscle, these are optimally located between thick and thin filaments and near the mitochondria. Glycogen is stored in the granules containing enzymes needed for its breakdown and storage. ATP provision in muscle is enhanced by the breakdown of liver glycogen during exercise – communication between these 2 tissues.

Question 15

Describe the synthesis and breakdown of glycogen (reaction, process and enzymes)

Question 16

Basic mechanisms regulating glycogen breakdown and resynthesis during and after exercise
-Exercise regulated the breakdown of glycogen

Answer 16

-Exercise regulates the breakdown of glycogen -> The rate of glycogen breakdown in skeletal muscle increases rapidly within seconds of muscle contraction die to the high demand for ATP. Glycogen breakdown is also increased in the liver to supply the muscle with more glucose

Question 17

Basic mechanisms regulating glycogen breakdown and resynthesis during and after exercise
-Glycogen phosphorylase activity in muscle is increased through (4)

Answer 17

-Glycogen phosphorylase activity in the muscle is increased by:
1. Increased Pi
2. Increased AMP/ATP ratio
3. Increased adrenaline
4. Increased Ca2+
-Glycogenolysis in the liver is increased by adrenaline (only systemic change)

Question 18

How glycogen synthesis is regulated during and after exercise
-Insulin independent (0-4 hrs) and Insulin-dependent (4-24 hrs)

Answer 18

-Glycogen resynthesis in skeletal muscle occurs in 2 phases: 1) insulin-independent and 2) insulin-dependent
1) Insulin-independent (0-4 hours):
1. Glycogen content of muscle
2. Glucose transporter-4 (GLUT4) in skeletal muscle
3. Glycogen synthase activity highest 30-60 minutes after exercise
4. Higher post-exercise blood flow
2) Insulin-dependent (4-24 hours):
1. Lower rate of synthesis than insulin-independent phase
2. Insulin exclusively drives glucose uptake (GLUT4), glycogen synthase activity and this glycogen resynthesis
3. Carbohydrate feeding accelerates this by maximising glucose and insulin levels in the blood

Question 19

Key phases of glycolysis and the steps regulated by exercise
(energy provision in muscle during exercise, hydride ion, glycolysis)

Answer 19

-Energy provision in muscle during exercise -> Breakdown glycogen to supply working muscle -> Utilise glycogen and muscle glycogen to supply muscle fibres with ATP
-Hydride Ion (H-) -> Breakdown of carbohydrates (and lipids and proteins) can supply protons and electrons for chemical energy provision (ATP). When a substrate is oxidised it gives up 2 hydrogen atoms, passing one as a hydride ion (:H-) to NAD+ (to make NADH) or FADH (to make FADH2) and the other is released as a proton (H+) to the aqueous environment (lowers pH)
-Glycolysis -> Is an anaerobic metabolic pathway with a low energy yield taking place in the cytosol. Reactants = glucose. Products = pyruvate (3 carbons), ATP and NADH.

Question 20

Key phases of glycolysis and the steps regulated by exercise
-Investment phase and section 1 and 2

Answer 20

1st section is the investment phase: 2 ATP molecules used to phosphorylate glucose and this thermodynamically favours catabolism: -∆G)
2nd section is the pay-off phase:
1. X4 ATP molecules
2. X2 NADH
3. X2 high energy triose sugars (3C)
4. 2 H+

Question 21

Key phases of glycolysis and the steps regulated by exercise
-Exercise speeding up glycolysis

Answer 21

-Exercise speeds up glycolysis -> Exercise can augment the glycolytic rate by 100 fold:
1. Substrate availability -> Increased glycogenolysis favours glycolysis to proceed
2. Physiological factors -> Greater blood flow with exercise increases flow of glucose molecules towards the active muscle
3. Cellular factors -> Increased glucose uptake by glucose transporters, such as GLUT4
4. Molecular factors -> Allosteric activation of pyruvate kinase and phosphofructokinase involved with glycolysis

Question 22

What is the krebs/citric acid cycle

Answer 22

-Krebs/ Citric acid cycle -> Citric acid is an aerobic metabolic pathway with a low energy yield taking place in the mitochondrial matrix. Reactant = Acetyl CoA. Products = ATP, NADH, FADH2

Question 23

Describe the process of pyruvate oxidation and how this links key metabolic pathways in the cytosol with the mitochondria

Answer 23

-Cytosol to mitochondria: pyruvate oxidation -> Shuttling of pyruvate to the mitochondria can yield large amounts of ATP. Mitochondria are the site of multiple oxidation reactions.
-Pyruvate can be oxidised to acetyl CoA via pyruvate dehydrogenase (PDH), in turn generating NADH (1 glucose, 2 pyruvate, 2 NADH)
-NADH is impermebale to the mitochondrial membrane

Question 24

Describe the Krebs/ Citric acid cycle and steps regulated by exercise

Answer 24

-A series of 9 reactions that oxidise acetyl CoA into carbon dioxide via a series of metabolites that produce electron carriers in the mitochondria – NADH and FADH2
-A small amount of ATP is produced, but 6 NADH and 2 FADH2 can then be utilised for a high energy yield in the mitochondria
-1 glucose produces 2 pyruvate and 2 acetyl CoA molecules
-The metabolites are completely recycled
-CO2 is produced when NAD+ becomes NADH. Carbon is lost from the compounds in the cycle.
-Enzyme 4,5,7 and 9 are key in the break down in the cycle
-The Krebs cycle (similar to glycolysis) can be upregulated by 100 fold during exercise by changes in key metabolites that modulate key enzymatic steps. Decreased ATP/ ADP and increased Ca2+.