Metabolism Flashcards
What are the four macromolecules?
carbohydrates, protein, lipids, nucleic acids
What is metabolism?
all the chemical reactions that occur in the body
What are the two principal forms of energy?
kinetic and potential
What is chemical energy?
potential energy stored in the bond of molecules
How is chemical energy released?
digestion of food converted to heat or mechanical energy
What is the human body’s main energy currency?
ATP
What is the term for the breakdown of ATP?
hydrolysis
Describe the makeup of ATP.
3 phosphate groups attached to adenine and 5 carbon sugar (ribose)
What enzyme catalyzes the breakdown of ATP?
ATPase
What is the main CHO for energy?
Glucose
What transport mechanism does glucose utilize?
facilitated diffusion
What is the typical glycogen value for a normally fed, untrained individual?
55-85 mmol/kg
What is the typical glycogen value for a normally fed, trained individual?
110-135 mmol/kg
What is the typical glycogen value for a well rested individual?
180 mmol/kg
What is the typical glycogen value for a CHO loaded individual?
220-240 mmol/kg
What nutrient is the most efficient due to its energy yield?
Glycogen
How can glycogen be metabolized?
both aerobically and anaerobically
Generally describe glycogen storage capacity.
it’s limited
What is the term given for glycogen synthesis?
Glycogenesis
What is the term given for glucose breakdown?
glycolysis
What is the term given to the process by which glycogen is broken down into G1P??
Glycogenolysis
Where can glycogenolysis occur?
liver or muscle
What is the term given to the process in which new glucose is formed from non-CHO sources?
Gluconeogenesis
Where does gluconeogenesis primarily occur?
liver
What does it signify when an enzyme has “kinase” in its name?
that it adds a phosphate
What does it signify when an enzyme has “phosphatase” in its name?
removes a phosphate
What does it signify when an enzyme has “phosphoylase” in its name?
splits a compound by adding a phosphate
How is CHO primarily stored?
in the form of glycogen
Glycogen breakdown begins by what event?
SNS/catecholemines releasing cAMP
cAMP binds to what enzyme for the first step of glycogen breakdown?
protein kinase A
What does protein kinase A do for the glycogen breakdown?
it adds a phosphate to glycogen synthase to inactivate it and phosphorylates phosphorylase kinase to activate which will activate glycogen phosphorylase for degradation to occur
What ion aids in glycogen breakdown and how?
Ca2+ phosphorylase activity
What stimulates glycogen synthesis?
insulin
By what mechanism does insulin start glycogenesis?
stimulates Protein phosphatase
What does Protein phosphatase do for glycogenesis?
- it removes a phosphate from glycogen synthase to activate it
- it inactivates phosphorylase kinase AND
- inactivates glycogen phosphorylase to pause glycogen degradation
True/False: Glycolysis requires oxygen.
false, can be anaerobic
What are the two main functions of glycolysis?
Produce ATP and pyruvate
Where does glycolysis occur?
in the cytosol of the muscle cell
What is glucose broken down into?
into 2 3-carbon pyruvates
Glycolysis is the only source of energy for what cell type?
RBCs
What is the first step of glycolysis?
Glucose enters the cell and in the presence of hexokinase becomes G6P and becomes trapped in cell.
What is the fate of G6P?
becomes pyruvate
What other reaction helps with glycolysis?
Glycogen -> G1P -> G6P
What are the three rate limiting enzymes for regulation of glycolysis?
hexokinase, phosphofructokinase, pyruvate kinase
Which enzyme catalyzes F6P -> F1,6 biphosphate?
PFK
What enzyme catalyzes phosphoenolpyruvate -> pyruvate?
Pyruvate kinase
What inhibits hexokinase?
G6P
What inhibits PFK?
ATP
What activates PFK?
AMP
What inhibits pyruvate kinase?
ATP and acetyl CoA
What activates pyruvate kinase?
AMP and F1,6BP
What other compounds are released during glycolysis?
NADH
How does NADH become?
NAD+ reacts with two H+ and it binds with one and accepts the electron from the other, reducing to NADH
What is the end results of glycolysis?
2 net ATP, 2 pyruvate, 2 NADH
What is the fate of pyruvate?
becomes lactate or is shuttled to the mitochondria for Krebs
What is the name of the similar enzyme to hexokinase that does the conversion of glucose to G6P in the liver?
glucokinase
Why does lactate form?
regenerate the NAD+ needed to continue oxidizing glucose
Lactate produces when there is a mismatch between what two things?
rate of pyruvate production and ability of PDH and mitochondrial shuttle systems to remove pyruvate and NADH
Lactate accumulation occurs when what events happen?
production exceeds clearance, insufficient O2 delivery, inadequate PDH activation
What are the three places lactate can be shuttled?
mitochondria, adjacent muscle fiber, and liver/heart/muscle cells
What ultimately happens to lactate?
is transported back to the liver for conversion back to pyruvate and then to glucose (via gluconeogenesis)
What is the fate of pyruvate?
form acetyl CoA
What enzyme catalyzes the oxidative decarboxylation of pyruvate?
pyruvate dehydrogenase
How many rounds of Krebs is in a cycle after glycolysis?
2 (1xpyruvate)
What is the relationship between exercise intensity and PDH activation?
Increases together (then stays stable)
What regulates PDH?
calcium, pyruvate, many other substrates and cofactors
Describe how the Kreb’s cycle works.
acetyl CoA combines with oxaloacetate to form citrate and as it converts back, it looses two CO2, releases 3 NADH, 1 FADH2, and converts one ADP to ATP
What is the end result of the Krebs cycle?
2 ATP, 6 NADH, 2 FADH2 (4 electrons each)
Describe how the Electron Transport chain works.
NADH and FADH2 turn back to their OG form (NAD+ and FAD+) and the H+ atoms are passed down the chain to form a proton concentration gradient to provide energy for ATP production, O2 serving as the final electron acceptor - forms water. As H+
ions flow down their gradient and back into the matrix, they pass through an enzyme called ATP synthase, which harnesses the flow of protons to synthesize ATP.
What happens if O2 is not available for the ETC?
if oxygen isn’t there to accept electrons, the electron transport chain will stop running, and ATP will no longer be produced
How many H+ pass through ETC for 1 ATP?
4
How much ATP is formed from NADH?
2.5
How much ATP is formed from FADH2?
1.5 ATP
What is the end result of one glucose molecule?
10 NADH, 10 H, 2 FADH2, and 4 ATP = 32 ATP
Name some inhibiting factors that control glucose oxidation.
glucagon (inhibits PFK), citrate (inhibits PFK), ATP (inhibits PFK and Pyruvate kinase), NADH (inhibits citrate formation and pyruvate dehydrogenase)
Name some stimulating factors that control glucose oxidation.
ADP (stimulates PFK)
What is the relationship between exercise intensity and energy source?
higher intensities rely more on muscle glycogen
What is the primary fuel source during high-intensity (85% VO2max) exercise?
muscle glycogen
What is the primary CHO fuel source that becomes most important after 3-4 hours of moderate-intensity (~70% VO2max) exercise?
blood glucose
What energy substrate is primarily utilized during rest-light to moderate intensity?
fats
In a person with a mixed diet, what is the approximate duration for exercise?
~ 180 mins
In a person with a carbohydrate diet, what is the approximate duration for exercise?
~240 mins
In a carbohydrate deficient diet, what is the approximate duration for exercise?
~90 mins, doesn’t sustain as well
What effect does eating before exercise have on exercise?
eating increases insulin which decreases blood glucose levels and if too close to exercise can lead to hypoglycemia
What effect does CHO feeding during prolonged exercises have?
Can prolong and extend ability to sustain exercise
For adequate glycogen resynthesis, when should CHOs be taken in?
as close to after as possible
What is the relationship between glucose uptake and glycogen use during exercise?
linear increase : greater intensity = greater post-exercise glucose uptake
What are the types of lipids?
fatty acids, triglycerides, and phospholipids
Which lipid(s) are high density energy store?
Fatty acids, TG (FA form TG)
Phospholipids contain precursors of many biologically active substances such as what?
prostaglandins, thromboxane, inositol triphosphate (IP3)
What do phospholipids do?
modulate the activities of membrane enzymes and transporters
What lipid soluble/derived substance controls fluidity and protein function?
cholesterol
What can cholesterol be synthesized from?
acetyl coA
Describe the structure of TGs.
glycerol backbone with 3 long chain FAs
What are the three common FA in humans?
Stearic acid, oleic acid, and palmitic acid
Which FA is 18C and unsaturated?
oleic acid (olive oil, nuts)
Which FA is 18C and saturated?
stearic acid
Which FA is 16C and saturated?
palmitic acid (fried foods, bad saturated fat)
What does TG break down into?
a Monoglyceride and 2 fatty acids
What catalyzes the breakdown of TG?
lipases
What does cholesterol ester break down into?
Chol and Fatty acid
What catalyzes the breakdown of cholesterol ester?
cholesterol ester hydrolase
What does phospholipids break down into?
lysolecithin and fatty acid
What catalyzes the breakdown of phospholipids?
phospholipase A2
Describe the lipid transport from the GI tract.
Bile salts dissolve the broken down lipids which allow them to enter the epithelial cells of the SI, next they re-esterfy into OG state where PL form a chylomicron around Chol E and TG for exocytosis into the blood via lymph duct
What happens next for lipid transport once the chylomicron enters the blood?
broken down into chylomicron remnants and FFA in the presence of Lipoprotein Lipase and enter adipose or muscle tissue
What happens to the chylomicron remnants in lipid transport?
GO back to the liver into remnant receptors via LPL and Apo E
What happens to the FFAs in adipose in lipid transport?
Go back to the liver directly
_ transports FFA from the liver to adipose and muscle.
VLDLs
In the presence of IDL, what happens to the transport of a lipid?
can wither be directly recycled to liver via Apo E OR in the presence of LPL become an LDL and go to muscle tissues, or do back to the liver via Apo B
What is needed for activation of LPL?
Apoprotein C
Chylomicrons obtain apoproteins C an E by transfer from what?
HDL
The majority of fat is stored where?
in TG in subcutaneous adipose tissue and skeletal muscle (as IMTG)
What must occur for TG to be metabolized?
lipolysis (TG - > glycerol + FFAs)
True/False: Fat has the highest energy value of the fuel types.
True
True/False: Fat is transported quickly.
False, since it’s mainly stored in muscle and not water soluble, there is a delayed transport of FFAs to the muscle
What are the steps for fatty acid utlizization?
- Mobilization (Lipolysis) 2. circulation 3. uptake 4. activation 5. Translocation and mitochondrial uptake 6. Beta-oxidation 7. mitochondrial oxidation
Describe the process of lipolysis.
lipases break down TG losing one Fatty acid at a time until there are 3 fatty acids
What are some stimulators of lipolysis?
Epinephrine, norepinephrine, glucagon, TSH, Exercise
What are some inhibiting factors of lipolysis?
Insulin, GH
At 25% of VO2max, what does the fatty acid circulation look like?
slight increase at start and remains fairly constant
At 65% of VO2max, what does the fatty acid circulation look like?
fairly steady increase is constant
At 85% of VO2max, what does the fatty acid circulation look like?
it decreases followed by a steady state then increases drastically and gradually comes down as exercise ends
Why is there such a steep slope for high intensity exercise in fatty acid circulation?
requirement of blood protein and blood so since blood is shunted away from adipose, there is not enough to release until the end of exercise
Describe the process of the uptake of fatty acids.
LCFA in the circulation plus VLDL TG (broken down by LPL) enter the cell via FAT/CD36
Describe the process of activation for fatty acid utilization.
LCFAs in the cell can either be re-esterfied and go to muscle, can bind to fatty acid binding protein and just store, or can be activated by the ACS (acetyl CoA synthase) for mitchondrial uptake
What transporter uptakes LCFAs to mitochondria?
CPT1
What happens during mitochondrial uptake?
LCFA + ACS = acyl CoA is taken up by CPT1 into the inner membrane where releases CoA and acyl binds with carnitine (acyl-carnitine). then translocase breaks down the acyl-carntine and the carnitine is recycled back and then CPT2 uptakes the acyl-CoA for Beta oxidation
What are some stimulators of CPT1?
acyl-coA, increase [LCFA], exercise
What are some inhibitors of CPT1?
Malonyl-CoA (intermediate in TG synthesis), acetyl CoA, decrease in pH, Free-coenzyme-A, lack of carntitine
Describe the process of beta-oxidation.
Fatty acyl-CoA passes through and via a series of four Rxn’s removes two carbons to form acetyl-CoA and reducing equivalents are produced (NADH and FADH2) and the fatty acyl-CoA is now two carbon atoms shorter and this repeats until it is totally degraded
How many rounds of Beta oxidation are required to break down the fatty acyl-CoA?
7
What is the end result of beta oxidation?
8 acetyl CoA, 7 NADH, 7 FADH2
How many ATPs does beta oxidation provide?
8 acetyl CoA = 96 ATP, 7 FADH2 = 10-11 ATP, and 7 NADH = 17-18 ATP
= 123-125 ATPs
What can occur when large quantities of FA become available?
ketosis
High levels of ketone bodies can lead to what?
ketoacidosis
What is the “re-assembly” of TG?
re-esterification
In muscle and adipose tissue, what is used for TG synthesis?
G3P from glycolysis
What is the trend around muscle TG content following exercise?
decrease in the hours following, maybe due to replenishing of the glycogen stores?
The breakdown of _ may provide additional energy to aid in muscle glycogen restoration.
IMTG
True/False: Adipose tissue can act as an endocrine tissue.
true
Adipose tissue secrete adipokines. What are those?
regulatory cytokines
What are the important adipokines?
Leptin, MCP1, and adiponectin
What does leptin do?
stimulates the hypothalamus that energy stores are too high and to decrease food intake and increase muscle-fat oxidation
What stimulates leptin secretion?
increase adipose tissue mass
What can occur to the leptin levels in obesity?
are chronically elevated and can become resistant
What can reverse leptin resistance?
regular exercise and omega 3 PUFA rich diets
What does MCP1 do?
increases monocyte infiltration into adipocytes which increase proinflammatory cytokines which can increase insulin resistance
What does adiponectin do?
the opposite of MCP1 - increases insulin sensitivity from decreasing vascular inflammation
What increases adiponectin serum levels?
weight loss
What are proteins broken down into?
amino acids
Muscle _ is dependent on the balance between protein synthesis and degradation.
Size
More synthesis of protein leads to what effect on muscles?
growth
More degradation of protein leads to what effect on muscles?
atrophy
Name a few examples of things that increase protein synthesis.
eating, exercise
Name a few examples of things that increase protein degradation.
unloading, starving
True/False: there is a continuous exchange between free amino acids and protein pools.
true, they are constantly being synthesized and downgraded
Where are the amino acid pools?
plasma, interstitium, muscle
What does albumin do for proteins?
provides colloid osmotic pressure
What effect does liver disease have on albumin levels?
can’t build up = decreases colloid osmotic pressure = edema
What does globulin do?
helps with immunity
What does fibrinogen do?
helps with blood clot formation
What are the mechanisms of altering protein content/composition?
- change gene profile 2. change breakdown rate of mRNAs 3. selection of specific mRNAs for translation and protein synthesis 4. selection of specific mRNAs for preferential degradation
Where do ionized amino acids circulate?
plasma (~35-65 mg/dL)
By what mechanism is transport of amino acids into cells?
Carrier mediated = facilitated diffusion or primary active transport
What effect does feeding have on muscle protein synthesis?
increases by 10-20% and decreases degradation by ~20%
How much protein is lost during overnight fasting?
~20%
What overall effect does protein have on exercise?
minimal energy disturbance = maintain net protein balance
In conditions where fuel oxidation doe not match ATP turnover rates, what occurs to the protein balance?
energy disturbance is large = negative protein balance
In a patient with McArdle’s disease, they lack the enzyme _ for glycogenolysis.
glycogen phosphorylase
What affect does resistance exercise have on protein turnover?
Simultaneous increases that last for >24 hours after exercise (highest @ first 2-6 hours)
One bout of resistance exercise can result in how much increases in MPS rates?
40-150%
What after effects does endurance exercise have on protein synthesis?
increase in mitochondrial proteins, no change in myofibrillar proteins
Describe the effects of aging on protein turnover.
aging = decreases physical activity = sarcopenia = decreased oxidative capacity (mitochondrial density) = decrease anabolic stimulus from resistance exercise and expression of mitochondrial enzymes from endurance exercise and decreases in protein diet EQUAL increase in MPS and decrease suppression of muscle protein degradation in response to meal ingestion
