8-10. Intermediary Metabolism Flashcards
What does intermediary metabolism refer to?
Metabolism of the 3 classes of high energy molecules or macronutrients (CHO, fats, proteins)
What is the energy content of ATP?
7.3 kcal per H2O used
Give 3 examples for cellular activities powered by ATP.
- Release of myosin, actin binding in skeletal muscle
- Metabolism
- Glucolysis, glycogenolysis
At rest, how much ATP does a muscle utilize? What does this demand increase to during a sprint?
- 1 mmol ATP/kg/min
- 240 mmol ATP/kg/min (4mmol ATP/kg/sec)
What does ATP stand for?
Adenosine Triphosphate
How is ∆G of ATP hydrolysis ideally positioned to act as both an energy receiver from metabolism and an energy donor to many other reactions?
- Intermediate positioned = between low energy and high energy phosphate compounds
- ATP can transfer phosphate group energy to low energy phosphate compounds
- ADP can accept phosphate group energy from high energy compounds
What are nucleosides?
Molecules that consist of an adenine base, the sugar ribose, and the nucleoside adenosine
In a cell, what does respiration represent?
Conversion of chemical energy of foodstuffs into a useful chemical form
In a cell, what does cell work represent?
Conversion of useful form of energy (from foodstuffs) to other forms of energy or work
What is ATP homeostasis?
Constancy of ATP concentration over wide variations of turnover
What is ATP’s concentration in most cells?
2-6 mmol per kg of tissue
What are the 3 primary energy systems in muscle that can generate ATP?
- Phosphagens = creatine kinase rxn, adenylate kinase rxn
- Anaerobic glycolysis = substrate level phosphorylation of CHOs
- Aerobic pathways = oxidation of CHOs and fat
What one factor determines which energy systems are utilized for energy during exercise?
Pathway used depends on the rate you need ATP
Which can produce ATP at a faster rate - phosphagens and anaerobic pathways or aerobic pathways
Phosphagens and anaerobic pathways
List the 3 primary energy systems in muscle that can generate ATP?
- Phosphagens
- Anaerobic glycolysis
- Aerobic pathways
What is phosphagen? Examples?
High energy phosphate compounds
- ATP
- Creatine Phosphate
List the 3 primary energy systems in muscle that can generate ATP.
- Phosphagens
- Anaerobic glycolysis
- Aerobic pathways
List the 2 pathways through which immediate re-synthesis of ATP occurs in the short term.
- Creatine kinase rxn
- Adenylate kinase rxn
In skeletal muscle, the activity of what enzyme exceeds that of all other enzymes?
Muscle creatine kinase
Where is creatine kinase found?
- Attached to the contractile filaments at the M-line
- Attached to the outer face of the SR
- Attached to the inner side of the sarcolemma
- W/in the sarcolemma
What is the concentration of creatine phosphate compared to ATP?
3-4x
In humans, what percent of the body’s creatine phosphate is found in skeletal muscle? Where is the rest found?
- 92-96%
- Cardiac tissue, brain, testes
What occurs during a creatine kinase rxn?
- Energy liberated from the hydrolysis of creating phosphate is used to resynthesize ATP
- Opposite rxn occurs (in recovery) to resynthesize creating phosphate from ATP
What occurs during an adenylate kinase rxn?
2 ADP —> (catalyzed by adenylate kinase) –> ATP + AMP
If cellular energy use (exercise) is sustained at high levels for more than a few second, the reserves of phosphagens will be inadequate to maintain ATP concentration. What is the body’s next metabolic line of defense?
Anaerobic pathways = glycolysis, glycogenolysis, pyruvate dehydrogenase
What is glycolysis?
Breakdown of glucose or glycogen to pyruvate (aerobic or lactate (anaerobic)
What is glycogenolysis? What occurs in the liver? Muscle?
Process by which glycogen is broken down to its individual glycosyl units
- liver = glycogen broken down to form glucose for release into the blood
- muscle = glycogen enters glycolytic pathway for glycolysis
What is glycogenolysis regulated by?
- Epinephrine
- Calcium
What is gluconeogenesis?
Process by which glucose is synthesized in the liver for release into the blood as glucose or for storage as liver glycogen
What is glycogenesis?
Process by which glycogen is synthesized from glucose
What is glycogen? Describe the structure.
- Polysaccharide
- Composed of hundreds of glucose molecules joined end to end w/ prevalent branches
What are glycosyl units?
Glucose units
What is glyogenin?
Central protein upon which glycogen is built in tiers around
Why is glycogen so heavy?
1 gram of glycogen has 2.5-3 g of associated water
Where is glycogen primarily stored?
Liver and skeletal muscle
What is euglycemia? Range?
- Normal blood glucose concentration
- 5-6 mM or 90-108 mg glucose/dL blood
Following a meal, what can blood glucose concentration increase to?
9mM or 160 mg/dL blood
How much can blood glucose concentration increase due to uncontrolled type I diabetes?
20mM or 360 mg/dL
How much can blood glucose concentration increase due to type II diabetes?
7-9 mM or 126-162 mg/dL
What is hyperglycemia?
Elevated blood glucose levels
What is hypoglycemia? Range? When can it occur?
- Blood glucose levels below 2.5 mM or 45 mg/dL
- Can occur if you don’t eat for long periods of time or you exercise for hours w/o ingesting CHOs
What percentage of glucose uptake occurs in skeletal muscle?
80%
Where is glucose uptake insulin-dependent?
- Muscle
- Heart
- Fat
Where is glucose uptake insulin-independent?
- Brain
- Liver
- Kidney
- Red blood cells
What is the main regulator of glucose transport in the resting muscle?
Insulin
How does glucose’s polarity affect its ability to diffuse across the plasma membrane?
- Polar
- Diffuses very slowly across membrane
- A fam of membrane transporters facilitate diffusion
How many steps are there in glycolysis?
10
Where does glycolysis occur?
Cytosol
Anaerobic vs. Aerobic glycolysis
- Anaerobic = no oxidation of glucose, FASTER
- Aerobic = oxidative capabilities, SLOWER
What are the 2 primary fuel sources for glycolysis?
- Muscle uptake of blood glucose
- Glycogenolysis
What is the role of glycolysis?
- Production of ATP
- Production of cytosolic reducing equivalents in the form of NADH
- Production of pyruvate (can be converted to acetyl CoA and used in the Krebs Cycle)
What governs the rate of glycolysis?
Energy needs of the cell
What does the regulation of glycolysis depend on?
Concentrations of glucose, glycogen, glucose-6-phosphate, ADP
Regulating what key enzymatic reactions regulates glycolysis?
- Hexokinase
- Phosphofructokinase
How is glucose taken into skeletal muscle and trapped there? What hormone and enzyme is involved?
- Via GLUT-4 transporters which are induced by insulin
- Glucose converted to glucose-6-phosphate by hexokinase
- No reverse enzyme in muscle to convert back to glucose so it stays in the muscle
How is the breakdown vs. synthesis of glycogen controlled?
LOOKUP
Name 2 intracellular indicators of a high rate of energy expenditure that shift the glycogen enzyme system towards glycogen breakdown.
LOOKUP
As glucose enters into the glycolytic pathway, what is the small difference in the energetic cost of getting started, depending on whether the glucose enters from the blood or from the muscle glycogen?
- Blood glucose = costs 2 ATP, yields 2 ATP
- Muscle glycogen = costs 1 ATP, yields 3 ATP
Describe the energy investment and energy generation phases of anaerobic glycolysis.
- Energy investment = -2 ATP if from blood glucose, 1 ATP if starting from glycogen, hexokinase, phosphofructokinase
- Energy generation = 4 ATP, 2 NADH, 2 pyruvate
What is the inhibitor of hexokinase?
Glucose-6-phosphate
What are the stimulators of phosphofructokinase?
- ADP
- Inorganic phosphate
- AMP
What are the inhibitors of phosphofructokinase?
- ATP
- CP
- Citrate
What is the stimulator of pyruvate kinase?
ADP
What are the inhibitors of pyruvate kinase?
- ATP
- CP
What is the inhibitor of lactate dehydrogenase?
ATP
What are the stimulators of phosphofructokinase? What do these say about intracellular energy status
- ADP
- Inorganic phosphate
- AMP
- Need more ATP
What are the inhibitors of phosphofructokinase?
- ATP
- CP
- Citrate
- Have enough ATP
What is the inhibitor of lactate dehydrogenase?
ATP
What is the crucial, regulated, and rate-limiting enzyme of the investment phase of anaerobic glycolysis?
Phosphofructokinase
What is the crucial, regulated, and rate-limiting enzyme of the investment phase of anaerobic glycolysis?
Phosphofructokinase
Name at least 2 short term advantages of anaerobic glycolysis in sustaining rapid generation of ATP from glucose.
- The K’eq is large so the rxn actively proceeds to completion
- Formation of NAD+ allows for recycling of NAD+ to supply substrate for glycolysis (energy generation phase)
What are the 2 potential fates for lactate?
- Intracellular transport
- Extracellular transport
Why is lactate good?
- Reduced form of pyruvate
- Carries a lot of energy
Describe the lactate shuttle.
- Lactate often produced by fibers w/ low mitochondria content
- Lactate diffuses out of these fibers to fibers of high mitochondria content via lactate shuttle
During what states is glycolysis the major energy-yielding pathway?
- During rapid transitions in muscle activity from rest to exercise, or from one exercise intensity to a higher intensity
- During exercise when oxygen is limited as a substrate for oxidative phosphorylation-isometric contractions
- Aerobic glycolysis, producing pyruvate, during steady state exercise when VO2 is about 60% or more of VO2max
Describe the energy balance (in ATP in, out, and net) of glycolysis from glucose to lactate.
- Glucose –> Glucose 6 phosphate = -2 ATP
- Glucose 6 phosphate –> pyruvate = +4 ATP
- Pyruvate –> lactate = 0 ATP
- NET = +2 ATP