Lecture 3, Energy Metabolism

Question 1

Metabolism

Answer 1

the series of chemical reactions in a living organism that create and break down energy necessary for life (the series of all reactions within the body)

Question 1

Metabolic Rate

Answer 1

rate at which your body expends energy or burns calories (how many calories our body burns and needs) - refers to how much energy our body requires throughout the day

Question 2

What are the two classes of biochemical reactions that make up metabolism?

Answer 2

anabolism and catabolism - reactions that are used to generate the molecule called ATP which is the energy currency of the cell
- anabolism is making complex molecules from simpler ones which generally requires an input of energy (using amino acids from food and creating more complex chains of proteins) and catabolism take a complex molecule and breaking it down into a simpler form which normally help us make energy (take the energy that are stored with the bonds of food to make energy within the form of ATP

Question 3

Anabolism - “Growth”

Answer 3

• set of metabolic reactions that require energy to synthesize new molecules from simpler precursors
• food intake sparks anabolism through biosynthetic pathways
• a set of reactions that make something new from precursors

Question 4

Catabolism

Answer 4

• set of destructive metabolic reactions that transforms fuels into cellular (chemical) energy
• take something complex and extract the energy from that complex molecule by breaking it down and making ATP that we can use for energy
  examples in metabolism: glycogenolysis and glycolysis (lysis should be giveaway that you are looking at a catabolic reaction)

Question 5

Glycogenolysis

Answer 5

the breakdown of glycogen to glucose (long complex molecule of glycogen and breaking it down into simple units of glucose to then use for energy and fuel our bodies)

Question 6

Glycolysis

Answer 6

the breakdown of glucose / glycogen to pyruvate (producing 2 3-carbon pyruvate)
- splitting apart of glucose or sugar
- there are 6 carbons in a glucose molecule - glycolysis is splitting that glucose molecule right down the middle producing 2 3-carbon pyruvate
- glycogen is stored in the muscle and liver primarily (if we store all those long chains of glycogen as simple molecules of glucose, it is going to expand because it is taking on a lot of water which can lead to explosion so it is usually stored as glycogen)

Question 7

Chemical Energy

Answer 7

energy is extracted from food in three stages:
1. digestion, absorption (breaking down all of our food pieces into something digestable) , and transportation of energy-yielding nutrients (transport those nutrients across many organs and membranes and throughout the body) - physically break it down and bring it to where we need

2. production of metabolites (end product of metabolic reactions) - metabolite is any product or reactant that is a part of a biochemical pathway (infinite number within our body)
3. body’s cells can use energy-producing metabolites to completely breakdown metabolic intermediates to a form of energy that the body can use – Adenosine Triphosphate (ATP)

Question 8

Functions of Chemical Energy

Answer 8

the chemical energy derived from food fuels these essential body functions:
1. breathing
2. blood circulation
3. body temperature maintenance
4. oxygen delivery to tissues
5. waste removal
6. synthesis of new tissue
7. repairing damaged or worn-out tissues
my notes:
- we use ATP and energy for a lot of stuff listed above
- ATP comes from stored glycogen and lipid (fat) is used for energy when not supplying the body with a means of energy
- we constantly tap into stored energy to exist

Question 8

Adenosine Triphosphate (ATP) ~ 100g (that is how much is stored)

Answer 8

• “molecular unit of currency” - the primary energy molecule powering cellular functions
• production of ATP is the fundamental goal of energy-producing pathways in metabolism
• three phosphate groups attach to the organic molecule adenosine via a high energy phosphate bond
• phosphate bonds break – energy (and Pi) are released

my notes:
- the main energy currency the body works in
- we have mechanisms that continually replenish any energy we use up as we are constantly using ATP (glycolysis and oxidation of stuff)
- ATP is used when some ions need to be moved, muscle contractions etc.
- our body is always breaking down ATP but because we do not store a lot our body is good at resynthesizing it
- if we have 2 molecules of ADP we can turn that too ATP through the help of enzymes

Question 9

Cell Structures and Organelles

Answer 9

• the energy generating reactions happen in specific compartments
• mitochondria - krebs and electron transport chain
• cytosol (cytoplasm) - all the space that surround the organelles, this is where soluble glycolytic enzymes are located - glycolysis occurs in the cytoplasm
• energy generated organelles are located right where we using energy (near myofibrils, sarcoplasmic reticulum, sodium/potassium ATPase)

Question 10

What are the 3 pathways our body can remake ATP?

Answer 10

3 pathways: phosphocreatine (use of 1 enzyme), anaerobic glycolysis (use of about 10 enzymes) and oxidative phosphorylation
- each singular pathway provides a majority of energy at a different point in time, there is usually a combination of the 3 providing energy but what varies is the proportion of supplying energy, the duration and area under the curve is different, inductions differences (fast for ATP-PCR, medium for glycolysis, slowest for oxidative phosphorylation)
- each of these different systems are differing in their complexity (takes a little longer the more complex the metabolic system is)

Question 11

1. Phosphagen Energy System

Answer 11

• uses phosphocreatine exclusively to regenerate ATP in muscle tissue, simple chemical reaction (not a metabolic pathway)
  phosphocreatine
• split into creatine and a Pi by creatine kinase
• the additional Pi from the phosphocreatine compound used to resynthesize ADP into ATP
• occurs in the mitochondria and cytosol (primarily where phosphocreatine acts - mainly occurring in myofibrils in cytosol)

my notes:
- sprinting (10-12 seconds) uses the phosphocreatine system exclusively to fuel movement as it is quick and powerful - activities that are burst in nature like sprinting and olympic lifting
- the creatine molecule through the action of creatine kinase simply takes phosphate group and gives it to a used up ATP in the form of ADP
- when starting activity we immediately breakdown ATP to ADP and a phosphate group is given up by the phosphocreatine to use more energy (enzyme that is responsible for transferring that phosphate group is creatine kinase)
- primarily making ATP for about 10 seconds

Question 12

2. Glycolysis

Answer 12

• glycolysis: one molecule of glucose is converted into two molecules of pyruvate, two hydrogen ions and two molecules of water (splitting of 6 carbon molecule to 2 3-c pyruvate and makes a net of 2 ATP’s)
• fuels all-out exercise efforts after phosphagen system has been exhausted (approx. 15 seconds)
• features a 10-step process, occurs in cytosol (move a molecule of glucose and metabolize it into something a bit more simpler)
• stimulated by epinephrine (flight or fight - something is wrong we need to move so start producing energy) and glucagon (made in the alpha cells in the pancreas - telling the liver to start to breakdown glycogen and split that our as glucose into circulation for all of our muscles to start using)
• overall: converts one 6-C glucose molecule to
  ◦ 2 x 3-C pyruvate molecules
  ◦ 2 x net ATP (4 produced but 2
  consumed in stage 1)
  ◦ 2 x NADH (reduced form - high
  energy form) (or NAD+ -
  oxidized form) - important for
  making even more ATP

my notes:
- 400m sprint - glycolysis acts for about 20 seconds to 2 minutes
- takes a little more time to get going and energy investment to kickstart it
- the regulation of glycolysis is a bit more complex as it involves hormones

Question 13

2. Fate of Pyruvate

Answer 13

• pyruvate is being produced in the cytoplasm
• glycolysis is an anaerobic process that does not need oxygen to proceed
• when there are sufficient levels of oxygen delivery to the cell, pyruvate can enter into mitochondria to further breakdown (the entering of pyruvate into the mitochondria is dependent on sufficient levels of oxygen)
• if there is not sufficient oxygen the pyruvate it transferred to lactate (uses up an NADH)
• pyruvate is shuttled across the mitochondria and it is decarboxylated where there is an enzyme that snips off a carbon molecule to produce CO2 which we blow off during exhilation and it is converted to acetyl CoA (2 carbons in length) - 2 molecules of acetyl CoA are made for every glucose
• 2 pyruvates are made from one glucose which are then decarboxylated to make 2 molecules of acetyl CoA
• the enzyme that does it pyruvate dehydrogenase complex (PDH) - takes in pyruvate, cuts a carbon and makes acetyl CoA (that process is where we get another molecule NADH)

Question 14

2. Pyruvate Conversion to Acetyl CoA

Answer 14

• catalyzed by pyruvate dehydrogenase complex (PDH or PDC) - the mitochondrial gate keeper (responsible for shuttling that carbon into mitochondria where it is further broken down - cuts off a single carbon molecule and releases it as carbon dioxide (you are breathing off) then that pyruvate is converted to acetyl CoA (two carbon molecule that goes through the Krebs cycle to produce more ATP))
• regulated by energy status of the cell (to decide whether pyruvate dehydrogenase should take in pyruvate)
  ◦ high ATP will slow down PDC activity
  ◦ high ADP levels will speed it up
  my notes:
• pyruvate is produced in the cytosol and after that that pyruvate carbon needs to enter the Krebs cycle (takes placed within the mitochondria specifically mitochondrial matrix)
• if ATP concentrations are high that means we have enough energy and we get less pyruvate carbon coming into mitochondria
• when ATP is broken down we get ADP and when we want ATP we take ADP to make it
• if ATP concentrations are high this is a signal to say we have energy and we have less pyruvate coming into mitochondria
• if ATP is low then the high ADP indicates that we need to speed up and signals PDH to start shuttling in pyruvate to then convert to acetyl CoA and start producing more energ

Question 15

3. Aerobic Energy System (long distance running)

Answer 15

• most complex of the three energy systems – consists of the Krebs cycle and the electron transport chain
• can produce ATP from any macronutrient using different pathways (glycolysis uses carbohydrates exclusively)
• max rate of ATP production much slower than phosphagen and anaerobic systems – dependent on aerobic capacity / fitness (cardiorespiratory fitness)
  *aerobic capacity: the maximum amount of oxygen (mls) an individual can use in 1 minute per kg body weight (ml. kg-1. min-1) - the better someone’s oxidative capacity the better they can use this system

my notes:
- when oxygen is not limiting we rely heavily on the aerobic system
- the aerobic energy system can use any macronutrient to produce ATP (but protein is not the preference, typically fat and carbohydrate) unlike anaerobic because it uses only carbohydrate
- our aerobic energy system is largely influenced by our fitness (whether or not they are good at shuttling the pyruvate carbon into the mitochondria - well trained athletes are very good at doing this)

Question 16

Aerobic Energy System (continued)

Answer 16

• the aerobic system’s capacity to make ATP is unlimited when adequate oxygen is available
• the ATP production system of choice when the body is at rest (burning a combination of fats and carbohydrates for energy as your are resting)
• can easily access carbohydrate and fat stores to meet the body’s chemical energy needs

Question 17

3. Krebs Cycle

Answer 17

2 pyruvate: (for every glucose consumed)
* 2 x ATP
* 6 X NADH
* 2 X FADH2

my notes:
- pay attention to stars as they are main energy producing steps (the main regulatory steps)
- 1. as that pyruvate is shuttled into the mitochondria it needs to have a carbon taken off by PDC which is taken out as CO2 which converts pyruvate (3 carbon) to acetyl CoA (two carbon) - in the first step NADH is also formed
- 2. acetyl CoA enters the mitochondrial complex where it is ready to cycle into the Krebs cycle (then it is converted to multiple different intermediates)- 3. it is combined oxaloacetate (4 carbon molecule) which gives you are molecule with citrate (6 carbon molecule) - we get the production of several other compounds later (citrate synthase takes acetyl CoA and oxaloacetate to attach them together)
- ATP is really only produced where we convert succinyl-CoA to succinate but we are producing these reducing equivalents at many different steps (NADH, FADH) which can be later used to convert to energy
◦ NADH and FADH production: isocitrate to alpha-ketoglutarate, succinate to fumarate and fumarate to oxaloacetate
- you do not get a lot of ATP produced from the Krebs cycle
- this process is happening twice as every glucose produces 2 pyruvate which also produces 2 acetyl CoA
- oxaloacetate has to continually be available (when carbohydrate is stripped we need to have a mechanism for preventing drops in circulating glucose - can be made back into glucose as it shuttled off to liver if we are short of that - but if that happens we need ways to replenish oxaloacetate - the amino acids can provide sources of carbon)
- for amino acids we need to remove nitrogens groups first which is called deamination where it is excreted as urine - amino acid carbon backbone can enter Krebs cycle at various stages

Question 18

Electron Transport Chain (ETC) and Oxidative Phosphorylation

Answer 18

• high energy electron carriers (NADH and FADH2) transfer electrons to the ETC
• the ETC is made up of a series of complex protein channels (5) on inner mitochondrial membrane (the channels are embedded within the membrane and they take electrons from matrix and pump them up in the intramembranous space)
• NADH and FADH2 (made in glycolysis and Krebs cycle) are oxidized releasing H+ and electrons (made to release electrons and hydrogen ions which develops electrochemical hydrogen gradient - when NADH and FADH and converted to NAD+ and FAD+ releases hydrogens which get pumped up which creates a lot of potential energy that is harnessed by ATP synthase)
• passing of electrons down the chain creates an electrochemical gradient
• H+ are forced to move from the matrix to the inner mitochondrial space
• build up of pressure forces H+ ions through protein channel ATP synthase
• harnesses energy to fuel the final step in ATP formation, known as oxidative phosphorylation when inorganic phosphate binds to ADP forming ATP

my notes:
- this system uses energy that is stored within the high energy intermediates specifically NADH, FADH2 for nitrogen pumping and electron transport to produce large amounts of ATP
- ATP synthase converts potential energy into kinetic energy which forms large amounts of ATP

Question 19

Diagram - Electron Transport Chain

Answer 19

• mitochondrial complex is the beige
• complex 5 is ATP synthase what is really making the ATP but needs all steps prior
• in Krebs cycle we have the production of reducing equivalents which is NADH and FADH2 - the hydrogens that are attached to them are ripped off which create electrons and protons - pass from complex to complex which creates an electrochemical gradient which pushes all of those hydrogens that are released from mitochondrial matrix to the inner membrane space (really acidic)
• this process is producing a hydrogen gradient using up all the hydrogens from the equivalent (wants to flow from high concentrations to low concentrations to reach equilibrium)
• as the hydrogens flows down its concentration gradient (when the gate opens - ATP synthase) it converts potential energy to kinetic energy to convert ADP back to ATP

Question 20

Net ATP from the Complete Aerobic Oxidation from One Molecule of Glucose

Answer 20

• one molecule of NADH makes 2.5 molecules of ATP
• one molecule of FADH2 is responsible for making 1.5 molecules of ATP
• glycolysis is happening in the cytosol and after NADH has to be shuttled into the mitochondria (the two different pathways by which that happens is called the malate aspartate shuttle (takes NADH breaks it down to NAD to move it from cytosol to mitochondria and then once it mitochondria it is converted back) glycerol phosphate shuttle (NADH breaks it down it NAD and reforms FADH2 in mitochondria so then the amount of ATP produced changes)
• in glycolysis we have two ATP made directly and either 3 or 5 from the high energy intermediates (NADH, FADH2)
• depending on what shuttle is used it either makes 3 or 5 ATP
• if we are using glycogen (bypasses the hexokinase step) we end up with 31-33 because we do not give up the original ATP as an investment stage

Question 21

Chemical Energy Derived From Carbohydrate

Answer 21

carbohydrate: sugar units
most cells in the body extract energy from carbohydrate via four metabolic processes:
a. glycolysis
b. pyruvate to acetyl-CoA
c. the Krebs cycle
d. the electron transport chain (ETC) and oxidative phosphorylation
- all the pathways that help us extract energy from carbohydrate

Question 22

Chemical Energy Derived from Fats

Answer 22

• stage 1: lipolysis - triglycerides are broken down into glycerol and fatty acids in the mitochondria
• glycerol (3-C molecule) – easily converted to pyruvate (3 carbon) in liver (3 carbon backbone can be recycled back into pyruvate to be made back into glucose under glucose sparing conditions) - we can use carbon in lipids for energy by creating pyruvate to then be catabolized or that pyruvate could be used to reform glucose
• most of the foods that we eat and fats that we burn are in the form of a triglyceride
• triglyceride is one glycerol (3 carbon molecule- backbone) attached to 3 fatty acids
• lipolysis the splitting apart of this triglyceride molecule to make ATP that happens primarily in the mitochondria

Question 23

Chemical Energy Derived From Fats (stage 2-4)

Answer 23

• stage 2: fatty acids are linked to coenzyme A (requires 1 ATP investment) = Fatty Acyl-CoA
  ◦ activating that fatty acid tail once it is snipped off in order to be used for energy
  ◦ these substrates need to move from cytosol to mitochondria - we need to be able to move carbon from one cellular component to other
  ◦ upfront energy investment of 1 ATP
• stage 3: Fatty Acyl-CoA interacts with carnitine and can cross into mitochondrial matrix (carnitine shuttle)
  ◦ the carnitine attached onto fatty acid can help shuttle the fatty acid chain from cytosol to mitochondria
  ◦ there are different layers of regulations (breaking apart of triglyceride, attaching of acetyl CoA, finding a way to get it from cytosol to mitochondria) in order to use lipids
  ◦ once that molecule is inside mitochondrial matrix there is a bunch of enzymes that snip apart that fatty acid tail into 2-carbon molecules of acetyl CoA
• stage 4: beta-oxidation: breaks down fatty acids into acetyl-CoA for entry into the Krebs cycle as previous
  ◦ cuts off all of those fatty acid chains into multiple 2 carbon acetyl CoA molecules
  ◦ can make up a lot of acetyl CoA from one fatty acid tail
  ◦ fatty acid carbon is use to make acetyl CoA in order to turn the cycle which essentially produces the energy from the triglyceride

Question 24

Chemical Energy Derived From Fats

Answer 24

• beta-oxidation: breakdown of fatty acids into acetyl Co-A. repeated until 2-C remain
• ATP produced depends on the length of the fatty acid (4 –26 carbons) - more carbons = more ATP
  ◦ e.g. 18c stearic acid (18 chain carbon fatty acid) = 120 ATP molecules
  ◦ 1 chain of acetyl CoA can make 9 molecules of acetyl CoA
  ◦ makes 9 molecules of acetyl CoA
  ◦ if stearic acid exists as triglyceride (3 fatty acids combined to a glucose) you can make 3 times that (360 molecules of ATP) if the triglyceride if break down all 3 of the fatty acids
• process requires oxygen and is coupled with carbohydrate availability / blood glucose
• we need a sufficient level of carbohydrate to have an adequate amount of substrates when we want to use fatty acids
• we do not use up acetyl CoA if we do not have enough oxaloacetate (gluconeogenic precursor) - if we do not have enough glucose in our system we do need up producing enough of oxaloacetate and we want to catabolize acetyl CoA, it is not there to be converted to substrate (essentially are missing our reactants if carbohydrates are low)
• this is the reason why fat is much more energy dense than carbohydrates and proteins as there are way more carbon contained within them that is used to make ATP

Question 25

Chemical Energy Derived From Protein

Answer 25

• proteins are not stored but oxidized to make ATP or converted to new proteins for the growth and repair of the body
  1. amino acids stripped of their nitrogen component (deamination)
• we remove the nitrogen group we get deamination

2. remaining carbon skeleton can enter the breakdown pathways of the Krebs cycle at many different points
3. nitrogen component is converted to ammonia and then urea and excreted
4. ATP generated depends on stage AA enters the Krebs cycle – small compared to carbohydrate and fats
   * since there are entering from one so many different points we do not get one big representation of amino acids

Question 26

Benefits of Endurance Training

Answer 26

1. ↑ number and size of mitochondria (as we exercise regularly we end up having more mitochondria and greater size - our body becomes more efficient as we increase our mitochondria and sensory of enzymes)
2. ↑ concentration of glycolytic enzymes (we are still using some amount of carbohydrate still even with endurance training - coordinated up regulation in the amount of proteins responsible for making ATP from glycolysis, Krebs, electron transport chain)
3. improved aerobic efficiency (waste a lot less energy completing work - getting a molecule of glucose converted to 32 ATP)
4. improved electron delivery to the ETC
   - through endurance training changes that happen to oxidative metabolism and enzymes that regulate it
5. ↑ ability of the muscle to oxidize lactate (oxygen delivery which helps us oxidize lactate to take pyruvate into mitochondria)
6. improvements in the heart’s stroke volume and angiogenesis
7. improved capillary density and capacity to transport fatty acids from plasma to muscle cells (we are really good turning on glycolysis - getting fatty acids out of fat cells and delivering it to the blood to our working muscles
   - can create need blood vessels and capillaries
   - we become really good at mobilizing energy stores from non muscular sources (adipose tissues)

Question 27

Gluconeogenesis

Answer 27

• gluconeogenesis: creates glucose for the body from non carbohydrate precursors (glucose is vital to our existence) - carbon comes from sources that are not carbohydrate in nature
• makes glucose from other sources
  ◦ amino acids enter the Krebs cycle
  ◦ pyruvate (come from glycerol as they are both 3 carbon)
  ◦ lactic acid - Cori cycle in liver converts to lactic acid to glucose (lactate gets produced from anaerobic glycolysis in our muscles gets shunted in liver where it converts it back into pyruvate and then into glucose which can be shoot back in muscle)
  ◦ glycerol - converted in the liver to glucose
• a lot of systems to keep our glucose levels fairly stable
• happens primarily in the liver but also in the kidney (10%)
• anabolic reaction
• fats:
  ◦ fatty acids cannot be converted directly to glucose and the pyruvate → acetyl-coA reaction cannot be reversed (catabolism of fatty acids through beta oxidation can help fuel gluconeogenesis - a carbon in a fatty acid is not getting recycled back into glucose it is still important for providing ATP that is required to make ATP even though it cannot be reversed and used itself)
  ◦ the glycerol can be used but the fatty acid tails can only aid and provide energy that supports this process
• main site (90%) in liver, 10% in kidneys

Question 28

Glycogenesis

Answer 28

assembles glucose molecules into branched chains for storage as glycogen
- when demand for glucose ↓, glycogen synthase activity ↑ and restores glycogen stores in liver and muscle
- the process of creating an ever-growing strand of glucose - glycogen synthase is the enzyme that primarily does this
- glycogenesis is likely to occur when you are not using up or requiring a high degree of energy - when you just eat a meal as there is an abundance of energy substrates flowing around in our system (this is important in liver and muscles to create more glycogen) - replenish that we used up before we ate (pay back what we used up), after exercise as there is not an ATP demand at that point

Question 29

Lipogenesis

Answer 29

accelerated during times of excess calorie consumption; often leads to the gain of fat tissue due to excess acetyl-CoA molecules
- is the creation of lipid species (fats) - lipogenesis occurs when there is an energy surplus (create new energy substrate like glycogen and lipids that we can store for later use) or less energy demand (after feeding or recovery from exercise)

Question 30

Energy Balance

Answer 30

• this energy balance does not factor in social determinants for PA and health (you cannot just change your diet as it can be outside of your control)
• regulation of body weight is based on some rules of thermodynamics (however it is an exceedingly complex process)
• if you change your energy intake that can change your energy expenditure and vice versa

Question 31

Estimating Energy Expenditure

Answer 31

3 principle components of energy expenditure:

1. resting metabolic rate (RMR); 50 – 70% - maintain basic physiologic function
   - roughly makes up half of our energy expenditure
   - can use interchangeably with basil metabolic rate (all of the energy that is needed to simply exist) - that energy is used for things like ion cycling, synthesis of hormones, maintenance of tissues etc.
   - 50-70% of the calories we burn in a day come from this
2. thermic effect of food (TEF); 10%
   - how much energy it takes to breakdown food
   - eating is gaining calories but the process of eating and digesting food requires us to burn and take energy to breakdown all of the macromolecules into forms that are meaningfully used by our body
   - this can change depending on what composes of our diet (the percentage can change)
   - protein has the highest simulation energy - when we digest we end up spend up using a lot of energy to make it digestable and get it into a useable form so we are left with less calories to actually store
3. physical activity: non-exercise activity thermogenesis (NEAT) + Physical activity. 15 – 30%
   - can be subdivided into two components - physical activity and NEAT
   - neat is standing, moving from places, chewing, fidgeting (uses up energy - not a lot)
   - neat is not under conscious control - can be determined by social factor (does everyone have the ability to make modifications to increase neat)
   - our energy intake would have to match our energy expenditure if we want to maintain current body weight (it is not acute but rather long term)
   caloric intake and energy expenditure may not be identical on a daily basis but with weight stability it is balanced over time
   - if we want to be in state of energy balance how do we know how many calories to burn - in order to know that you need to know how many calories your body burns - indirect (V02 max test - measure of oxygen consumption where we can estimate energy expenditure), direct calorimetry (heat that is given off your body - requires expensive and complex methodologies) and pr