Bioenergetics part 2 Flashcards
What is energy released from macronutrients harnessed by our bodies to do?
Synthesise ATP
So ATP is carrier of energy from macronutrients
What is Adenosine triphophate made up of?
Adenine
Ribose
Phophate chain
How does ATP produce energy basically?
When you break phosphate bond lots of energy released
It’s the only compound that transfers chemical energy to energy requiring processes
Why do we use ATP?
Phosphate bonds trap large portion of potential energy from food
Easily transfers to other compounds to fuel endergonic reactions or raise compounds to higher activation levels (means that eventually energy release will be greater)
Example of this is storing glucose as glycogen
Explain how ATP is the energy currency, and reasons which it isn’t aswell?
Simplifies the coupling of energy producing reactions to energy requiring reactions (ATP can be used by all)
However, ATP cannot be accumulated, or transferred from cell to cell
Once the ATP has been used and no more can be generated, the cell dies (can’t go in debt)
What mechanisms do cells have to prevent death when run out of ATP?
Fatigue in ,muscle arrests ATP utilisation during physical activity
Maintenance of the ATP to ADP concentration ratio
This take precedence over cell function
Features about the ATP-ADP ratio?
Not equillibrium, 50/1 in favour of ATP
A system that is far from equilibrium is capable of doing work
Breakdown of ATP increases ADP concentration, but ATP is rapidly reformed
What are luxury reactions?
Physiological functions of the cells, that aren’t essential for that cell to survive (body may die)
What type of reaction is the breakdown of ATP?
Hydrolysis reaction, a Phosphate bond (terminal) is broken down when joined with water
ATP + H2O = ADP + Pi (inorganic Phosphate)
-(delta)G7.3kcal.mol^-1 amount of energy released
What enzyme catalyses ATP breakdown?
Adenosine triphosphatase (ATPase)
What can happen to ADP to release more energy?
A further phosphate group can be cleaved releasing more energy
Catalyzed by adenosine diphosphatase
This leaves adenosine monophosphate - AMP
Is a rare occurrencre as turnover of ATP (hydrolysis-re synthesis) is so effective
So only used in exhaustive situations
What does the enzyme adenylate kinase do?
Catalyse ATP regeneration from ADP
2ADP = ATP + AMP
Most important at beginning of exercise
Does ATP hydrolysis require oxygen?
No, Oxygen would take too lung too get to cells
Why haven’t human evolved to store more ATP instead of relying on re synthesis?
It would be too heavy, and therefore inefficient
How much ATP stored in the body at any given time?
80-100g
3mmol of ATP per kg wet weight muscle tissue
How is instant replenisment of ATP achieved?
PCr - phosphate phosphocreatine
Provides Phosphate group
Formula for ATP being used for biological work?
ATP = ADP + Pi + Energy
Catalysed by ATPase
Formula for ADP being turned into ATP?
PCr + ADP = Cr + ATP
Catalysed by creatine kinase
Where is Creatine Kinase found in abundance?
Locations of ATP hydrolysis and regeneration
How long does it take for PCr to theoretically deplete?
8-12 sec
What does PCr creating a buffer mean?
Gives time for other energy pathways to get going
What is the stimulus for Creatine Kinase activity?
Increase in ADP concentration (thus ATP Hydrolysis)
Describe the PCR shuttle?
Made in centre of Mitochondria
ATP leaves inner mitochondrial membrane, and binds to MiCK (mitochondrial creatine Kinase) in the inter membrane space
Then outside the mitochondrial membrane MMCK (muscle machinery Creatine Kinase) gives a Cr to MiCK, then PCr goes to MMCK,
Which then goes to ATPase and then the myofibril for contraction
The ATP has turned into ADP and returned inside the mitochondrial membrane to be re-synthesised into ATP
This reduces the distance ADP and ATP have to travel as they are very heavy, and Cr and PCr are lighter
What are the 3 macronutrients?
Carbs
Protein
Fat
What are the important 3 micronutrients?
Vitamins
Water
Minerals
Order from smallest to largest of energy production per gram?
Carbs
Protein
Lipid
Features of carbohydrate molecules?
Only Carbon Hydrogen and Oxygen
Has a Carbonyl group CHO, and a carbon skeleton
Isomers have same molecular formula and mass (C6H12O6)
Will either be mono, di or polysaccharides
Why do carbs provide energy?
We strip hydrogens from them and then strip electrons for electron transport chain
General formula for Carb?
Cn(H2O)n
Examples of monosachharides
Glucose
galactose
fructose
Example of a disaccharide?
Glucose + fructose = sucrose
Glucose + glucose = maltose
Example of polysaccharide?
Starch in plants, amylose and amylopectin
Glycogen in animals
Features of blood glucose?
Regulated by hormones
Primary cerebral fuel
Storage of carbs
What are the 3 storages of glycogen?
Blood glucose
Liver glycogen
Muscle glycogen
What’s glycogenenis?
Synthesis of glycogen from sugar molecules
What’s glyconeogenesis?
Formation of glycogen from amino acids, fats and other non carbohydrates
What’s glycogenolysis?
Breakdown of glycogen into glucose, to use it for energy transfer
Catalysed by glycogen phosphorylase
3 stages of extraction of energy from carbs?
Glycolysis
TCA cycle (Krebs)
Oxidative phosphorylation
Features of glycolysis?
Oxidation of glucose Start product can also be glycogen Takes place in the cytoplasm Aerobic glycolysis produces pyruvate Anaerobic glycolysis produces lactate
What does glycolysis require?
Glucose
Enzymes
Co enzymes
ADP
What does glycolysis produce?
Pyruvate
NADH
ATP
Does glycolysis require oxygen?
No but further stages do
1-3 steps of glycolysis?
Energy investment to recouped later:
- Catalysed by the enzyme hexokinase
- Catalysed by phosphofructokinase
ONLY STEP 3 REQUIRES ATP WHEN GLYCOGEN IS USED AS A SUBSTRATE
What is the primary regulator of the speed of glycolysis?
Phosphofructokinase
Steps 4-5 of glycolysis?
Cleavage of 6-carbon sugar to 2 3-Carbon sugars:
So rest of reactions will occur in duplicate
Steps 6-7 of glycolysis?
Energy generation: (remember all these steps are occurring in duplicate now)
- If the metabolic rate is high, the NAD+ can become saturated with H+, so that there is not enough free NAD+ available. This can cause a bottleneck at step 6 which will slow the rate of glycolysis
Steps 8-10
Remember all still in duplicate
Energy generation:
- pyruvate + ATP formed, catalysed by the enzyme pyruvate kinase
Net result of glycolysis?
1 molecule of glucose is turned into 2 pyruvate (or 2 lactate)
2ADP goes to 2 ATP (will be 3 for glycogen)
2NAD+ goes to 2NADH + H+
What can happen to pyruvate once it’s formed?
Can be turned into lactate, which also produces NAD+, which can then be used in step 6 of glycolysis
Can turn into Acetyl-CoA, produces NADH + H+, which can then be used in the mitochondrial electron transport chain
So what is made depends on if there is high NAD+ in the cell (Acetly-coA is made) or if there is high NADH + H+ in the cell (Lactate is made)
Overall energy yield of glycolysis?
2 ATPs
In glycolysis what are the rate limiting steps?
PFK at step 4
NAD+ in step 6
What are the ATP generating steps in glycolysis?
7 and 10
TCA cycle=
Krebs cycle
What happens directly after glycolysis?
If fatigued
Pyruvate turned into lactate, via lactate dehydrogenase
If not fatigued, pyruvate turned into Acetly-CoA + CO2, which then goes into the TCA cycle
Add more notes
Why do we make lactate when fatigued?
Glycolysis is faster than TCA and ETC
When metabolic rate is high NADH availability is high and NAD+ availability is low
This favours pyruvate to lactate
NAD+ produced will help maintain the glycolysis rate
H+ ions are released though, increasing acidity effecting enzymes can denature early ones in glycolysis
When is Acetly-CoA made?
When metabolic rate low and O2 availability high and so is NAD+
Favours the transport of of pyruvate to the mitochondrion where it is converted to Acetyl-CoA
Location of carbohydrate metabolism in a cell?
Cytosol for glycolysis, and therefore substrate level phosphorylation (Phosphocreatine hydrolysis and glycolysis)
TCA cycle and oxidative phosphorylation occurs in mitochondrion
Features of the TCA cycle?
Occur in mitochondrial matrix
Starts off with acetly-CoA
A cyclical process of 8 steps
Main purpose is to oxidise acety-CoA groups and strip off their electrons
Finishes with oxaloacetate
What’s cristae?
Folds in the mitochondrial matrix
Key steps of TCA cycle?
Step 1. Oxaloacetate reacts with acetyl CoA to form a 6-carbon molecule citrate
Step 3 produces CO2 and NADH
Step 4 produces CO2 and NADH
Step 5 produces one GTP
Step 6 produces one FADH2
Step 8 produces one NADH and regenerates oxaloacetate
What is net yield from one molecule of glucose?
36 ATP
Glycolysis 2
TCA 2
ETC 32
Ways to generate ATP and features of it?
PCr
Low capacity
Fast rate
Glycolysis
Intermediate capacity
Intermediate rate
Oxidative phosphorylation = etc
High capacity
Low rate
What are the differences between substrate level phosphorylation and oxidative phosphorylation?
Substrate level occurs in cytoplasm, PCR hydrolysis and glycolysis
Oxidative is in mitochondria energy comes from electron transport chain
Features of fat?
Composed of carbon , hydrogen and oxygen
Contain more hydrogen than carbohydrates
Types of fat?
Nuetral lipids - triglycerides
Compound lipids - phospholipids in cell membranes
Derived lipids cholesterol
More features of triglycerides?
Made up of 1 glycerol and 3 fatty acids
Hydrocarbon chain of fatty acid can vary - longer it is the more energy rich as more hydrogen and therefore more electrons
Where are triglycerides stored?
It's stored in adipose tissue: Subcutaneous fat (fat directly under the skin) Internal fat (Deposits internal organs)
In muscle cells
How are triglycerides made?
Condensation reaction releasing water between glycerol and fatty acid chain
Facilitated by substrate availability and hormonal regulation
Cells that form adipose tissue are?
adipocytes
Describe fat mobilisation?
Release of fatty acids from adipose tissue, triggered by hormone sensitive lipase (HSL)
Glycerol diffuses out
Free fatty acids travel in circulation bound to protein albumin
Triglycerides travel in lipoprotein complexes
What is lipolysis and what catalsyes it?
It’s the breakdown of triglycerides, catalysed by lipoprotein lipase
Equation for triglyceride catabolism?
Triglyceride + 3 H2O = Glycerol + 3 fatty acids
Describe how fats are used to generate ATP?
Catabolism occurs, glycerol and 3 fatty acids produced
Glycerol turned into Glyceraldehyde 3-phosphate, which is also the substrate in step 6 of glycolysis
Will then carry on the same path as glucose from there
The 3 Fatty acids are activated costing each an ATP
They then go into Beta- Oxidation producing 2 carbon Acyl groups which then react with CoA to form Acetly-CoA which is the substrate which goes into the TCA cycle so can just follow glucose from there
Also Beta Oxidation produces 2 H+ which will be used in the electron transport chain (transported by FAD and NAD+)
Features of Beta oxidation?
Occurs in mitochondrial matrix
Limiting rate of fatty acids entering TCA cycle?
There needs to be sufficient oxaloacetate to combine with the acetyl-CoA formed during Beta oxidation
What is Oxaloacetate regenerated from?
Pyruvate
What’s gluconeogenesis?
Glycerol, lactate and certain amino acids being converted to glucose in the liver
What’s the cori cycle?
2 lactate goes to 2 pyruvate goes to 1 glucose
Requires 6 ATP which is expensive so normally occurs resting after exercise
What’s lipogenesis?
Liver cells and adipose cells can synthesise lipids from glucose and amino acids
Can fatty acids be converted into pyruvate or oxaloacetate to synthesise glucose?
No
Protein functions?
There are Structural proteins - Actin and myosin in skeletal muscle
Transportation from the proteins haemoglobin and myoglobin as oxygen binds to them
Enzymes for all metabolic pathways
Hormones:
Neurotransmitters
Immune function
Structure of an amino acid?
alpha Carbon in middle
One side amino group (NH2)
Other side is carboxyl group (COOH)
Hydrogen above
Organic side chain bellow (C, O, H, N, S)
What happens when 2 amino acids bind together?
COOH terminal reacts with Amino terminal of other amino acid
Condensation reaction
Peptide bond formed
Describe Protein structure?
Primary:
Amino acid sequence
Secondary:
Hydrogen bonds between amino acids with the peptide chain
Alpha helices, beta sheets
Tertiary:
Attractions between a helices and beta sheets
Quaternary:
interactions between 2 or more peptide chains
Denaturation in protein?
Loss of structure and biological activity
However peptide bonds remain intact
Caused by temp or pH
Features of protein metabolism?
Unlike CHO and fats, protein is not stored as an energy substrate
Fast turnover rate
Rapid response to starvation and training
Regulated by hormones
Why is it difficult to determine energy yield of protein oxidation?
Nitrogen excretion requires ATP
Describe protein catabolism?
Amino acid is deaminated (removal of nitrogen)
Then will enter the TCA cycle at various stages:
- Pyruvate ( then go on to form acetyl-coA)
- Acetoacyl-coA ( then go on to form acetyl-coA)
- Acetyl-coA
- Intermediaries in the TCA cycle
Describe the process of nitrogen balance ?
Nitrogen removal from amino acids
Transported by alanine and glutamine
Urea cycle (ATP cost)
Dietary N input = N excetion to maintain balance
Negative Nitrogen balance means net loss of muscle mass
When we will protein contribute more to energy expenditure?
When CHO stores decrease
What is cellular oxidation?
Process aimed at providing energy to rynthesise ATP (oxidative phosphorylation) in the presence of Oxygen
Accomplished through the breakdown of CHO lipids and protein
What do we need for cellular oxidation?
Fuel Citric Acid cycle Co-enzymes (Cartier’s, NAD and FAD) The electron transport chain Oxygen
In the exam?
Describe electron transport?
Hydrogen atoms are stripped from CHO, lipids and protein (Citric acid cycle)
Co-enzymes NAD+ and FAD transport hydrogen to the ETC
Electrons are temporarily stripped from hydrogen and passed onto the ETC
The ETC is composed of 4 cytochromes (membrane bound proteins). Electrons are passed down them
At cytochrome 4 oxygen accepts the electrons and rejoins with H2 to form water
Describe ATP generation in ETC?
In 3 of 4 cytochromes the free energy release of electron transfer is accosiated with proton pumping from the matrix to the intermembrane space
This is a kind of active transport, as the protons accumulate outside the mitochondrial matrix
When they flow back down their concentration gradient, enough energy to phosphorylate ADP into ATP
(Happens in 1,3,4)
Where does FAD drop electrons?
Complex 2
So doesn’t help out at first complex
So net gain only 2ATP
Where does NAD drop electrons off?
First complex
Net gain is therefore 3 ATP
Equation for resynthesis of ATP?
NADH + H{+} + 3ADP + 3Pi + 1/2 O2. = NAD{+} + H2O + 3 ATP
What would happen if oxygen is limited in ETC?
Can no longer move electrons down the chain as C4 cannot be oxidised, so the rest will be backed up
NADH accumulates
NAD+ reduces
Flux through Krebs cycle is reduced
How do we continue exercise after O2 becomes limited?
Increase anaerobic energy turnover
Hydrogen removed from NADH by pyruvate resulting in lactate formation which generates more NAD+ which can be used in glycolysis and processes like this to generate more ATP, meaning pH will drop
Low pH is associated with reduced muscle function, so exercise tolerance is compromised
What’s an easy way to measure the rate of xeullar oxidation?
Consumption of oxygen
Explain the role of PCr hydrolysis at the onset of intense exercise?
Buffering - ATP replenishment
Signalling - early reactions involving PCr hydrolysis switch on glycolysis and oxidative phosphorylation1
How do kidneys regulate the acid-base balance?
Renal buffering is the only pathway to excrete H+ ions and thus neutralise acids other than the carbonic acid
Kidneys also facilitate the chemical buffering in the blood by releasing bicarbonate back into the back into circulation to mop up H+
Explain how ATP can be considered as an energy currency with 2 inconsistencies?
ATP simplifies the coupling of energy producing reactions to energy requiring actions
Unlike currency ATP can’t be accumulated or transfered
Credit is not permited, once ATP is gone cell function declines
What are the 4 main steps in the reciever donor cycle?
Extraction of potential energy from food
Conservation of this energy within ATP
Extraction of energy from ATP to perform biological work
ATP resynthesis via energy from food
