Lecture 8 - Metabolism Flashcards
What are the products of catabolism from Carbohydrates, fats & proteins?
CO2, H2O, NH3
What are the products of anabolism of amino acids, sugars, fatty acids and nitrogenous bases?
Proteins, polysaccharides, lipids and nucleic acids
What process breaks down simple sugars into energy?
- Glycolysis
- Krebs (TCA)
- Oxidative phosphorylation
Describe how many ATPs are produced in the process of breaking down simple sugars
- Glycolysis does produce ATP (2x ATP)
- BUT pyruvate to TCA (krebs) to oxidative phosphorylation gives a big payoff in terms of ATP
- approx 30 ATP
What is needed to metabolise molecules to get energy?
Energy carrier (ATP adenosine triphosphate)
ATP hydrolysis drives thermodynamically unfavourable reactions
How is ATP generated?
- oxidation of glucose
- oxidation of fatty acids
- oxidation of amino acids
What are common intermediates in ATP generation?
- Pyruvate
- Acetyl CoA
What are electron carriers?
NADH and FADH2
What is oxidation?
- GAIN of oxygen
- LOSS of hydrogen
- LOSS of electrons
What is reduction?
- LOSS of oxygen
- GAIN of hydrogen
- GAIN of electrons
What is glycolysis?
Degradation of glucose to pyruvate
- process results in formation of ATP and NADH
- 10 reactions (9 main ones + 1)
What are 2 phases of glycolysis?
- Preparation Phase
- Payoff Phase
What is preparation phase?
- conversion of one 6-Carbon (glucose) molecule into two 3-Carbon molecules of glyceraldehyde 3-phosphate (G3P)
- consume 2 molecules of ATP
What is payoff phase?
- conversion of glyceraldehyde 3-phosphate to pyruvate
- produces 4 molecules of ATP and 2 molecules
What is the net production from glycolysis?
Produces 2 ATP and 2 NADH molecules
How is glycolysis controlled?
Pyruvate Kinase
- inhibited by ATP and Acetyl CoA (high energy state)
- activated by fructose 1,6 biphosphate (low energy state)
Describe the positive and negative feedback used in controlling glycolysis?
Starting reactants PROMOTE conversion to Acetyl CoA (positive feedback)
BUT products INHIBIT conversion to Acetyl CoA (negative feedback)
How many carbons feed into the TCA (krebs cycle)?
2 (and 2 are pulled off in the oxidation phase)
Describe the products from one cycle of the krebs cycle
2 - CO2
1 - GTP or ATP
1 - FADH2
3 - NADH + H+
Glucose (6C) is split into 2x 3C of glyceraldehyde 3-phosphate
Products of 2 cycles:
4 - CO2
2 - GTP or ATP
2 - FADH2
6 - NADH + H+
What else supplies the Krebs cycle??
- proteins (amino acids)
- polysaccharides (glucose + other sugars)
- fats (fatty acids)
What is fat a combination of?
glycerol + fatty acid
Describe the breakdown of molecules
- involves 4 enzymes
- end result is the serial breakdown of the molecule in 2 carbon sections
- the acetyl-CoA produced enters the Krebs cycle
What can a fatty acid be turned into?
- only ATP (not glucose)
- glycerol (glucose - gluconeogenesis (6-8%)
What is a key point of amino acids in the krebs cycle?
Amino acids feeds into Krebs at different points
What occurs when when NADH+ & FADH2 are converted to NAD & FAD?
- they feed into the electron transport chain
achieved by means of 4 membrane protein complexes - electrons feed into complex 1 from NADH and complex 2 from FADH2
- process also establishes a protein gradient across the inner mitochondrial membrane - drives ATP synthase to produce ATP.
Generates a proton gradient between the inner and outer membranes
What is the purpose of oxygen in the electron transport chain?
Acts as the final electron acceptor - electrons convert oxygen to water
Describe how regulation occurs across the electron transport system
ADP/ATP levels are an important determinate of the rate of electron transfer
- At rest, the PROTON MOTIVE FORCE (PMF) is high, but due to high ATP levels, there is minimal flow of protons through the synthase, and low transfer of electrons.
- during exercise, ATP is consumed, ADP levels will rise, lead to proton movement through synthase, discharging the PMF.
- results in increased electron transfer to regenerate the PMF.
What are different functions of inhibitors?
- Electron transport inhibitor
- Uncoupling agent
- Inhibits ATP synthase
What type of inhibitor has the biggest effect?
- disruption of complex IV has the biggest effect. Carbon monoxide has a bigger effect on haemoglobin and therefore reducing O2 carrying capacity of blood.
- uncouplers - bodybuilders - very dangerous
- H+ gradient dissipated - therefore for the same amount of ATP, electron transport has to work much harder.
- generates lots of heat, it does work but can get out of control and you boil.
What is 2-4 dinitrophenol (DNP)?
Proton ionophore - a molecule that facilitates the movement of protons (H⁺) across a biological membrane.
Binds protons on one side of a membrane and moves to the opposite site where it loses the protons.
Highest probability to bind a proton where the H+ concentration is highest. It will dissipate the H+ gradient.
Is metabolism compartmentalized?
YES
What parts of metabolism occurs in the cytosol?
- glycolysis
- pentose phosphate
- fatty acid synthesis
What parts of metabolism occurs in the mitochondrial matrix?
- TCA
- Oxidative Phosphorylation
- B-ox of fatty acids
- Ketone body formation
What parts of metabolism occurs in the cytosol and the mitochondrial matrix?
- gluconeogenesis
- urea synthesis
What is ATP?
universal currency of energy
What different parts of the body is involved in metabolism?
- brain
- liver
- adipose tissue
- skeletal muscle
What occurs in the brain?
Uses glucose
What occurs in the liver?
- processes fats
- synthesises lipids, ketone bodies
- glucose
What occurs in the adipose tissue?
- synthesizes + mobilizes tricly-glycerols
What occurs in the skeletal muscle?
Uses ATP to do work
What is needed to move your muscles?
- your brain needs glucose
- your muscles needs ATP
Do all tissues use the same fuels to meet their metabolic needs?
Different tissues use different fuels to meet their metabolic needs
Describe how ATP is generated in the brain
Glucose and ketone bodies is converted to CO2.
What is used as a fuel for metabolism in the brain?
Glucose used in MOST conditions (even though ketone bodies are synthesized)
- except - ketone bodies replace glucose but only after several days.
What are ketone bodies?
contain ketone groups, produced from fatty acids by the liver
Describe metabolism in the kidney
- kidney produces urine - i.e. secrete waste products
- plasma is filtered 60x a day (water + glucose reabsorbed)
- starvation - major site of gluconeogenesis (1/2 of blood glucose)
Describe metabolism in muscle
Light activity:
- fatty acids
- ketone bodies
- blood glucose
These are converted into CO2
Heavy activity:
- muscle glycogen
This is converted to lactate
Describe exercise is muscle
1-2 mins - anaerobic - uses glycogen or serum glucose. Eventually switch to aerobic - oxidative phosphorylation
What is creatine is used as?
Creatine is used as a rapid energy supply to power the ATP-dependent motor that move your muscles.
- buys time for the glycogen stores to be mobilized
How is metabolism in the muscle and liver is linked?
The muscle needs the glucose produced from recycling the lactate
How does muscle get glucose?
Glycogen and from recycled lactate from the liver
Describe metabolic regulation on the FED state
Insulin - regulates the metabolism of carbohydrates, fats and protein. It promotes the absorption from the blood into liver, fat and skeletal muscle cells
Glucagon - increase the concentration of glucose ad fatty acids in the blood. Stimulates glucose production in the liver.
Describe the biological effects of insulin
Increase:
- glucose uptake
- glycogen synthesis
- protein synthesis
- fat synthesis
Decrease:
- gluconeogenesis
- glycogen mobilization
- lipid mobilization
- protein degradation
Describe the biological effects of glucagon
Increase:
- gluconeogenesis
- glycogen mobilization
- ketogenesis
- protein degradation
- uptake of amino acids
Decrease:
- glycogen synthesis
- protein synthesis
- fat synthesis
What does insulin do?
- signals to Glut-4 to uptake glucose
- GGLUT1,2,3 are insulin-independent
- controls amino-acid uptake and hence DNA-replication and protein synthesis
- numerous other effects on cells
Note where insulin-independent are located. All in tissues that need rapid glucose uptake (e.g. liver, erythrocytes and brain)
Where are GLUT4 glucose transporters found?
Skeletal muscle and adipose
Describe metabolic regulation in the early fasting state
As blood-glucose DROPS, insulin secretion DROPS and glucagon secretion rises.
In the liver, there are signals to breakdown glycogen, reduce glycolysis and increase gluconeogenesis
What occurs in the fed state?
glucose can be turned into fat in the liver and adipose (fat) tissue
What occurs in the fasted state?
When you fast, fats and glycerol and fatty acids are used to generate energy or glucose
- glucose made from fats (etc.) is used for muscle contraction
- BUT proteins can be broken into amino acids to make energy in the liver for example.
- FATTY ACIDS –> can be used in muscle to make Acetyl-CoA for aerobic metabolism
There is a complex interaction between liver and muscle to keep things going
Summarise metabolism
- different phases of metabolism produce different amounts of energy
- ‘starting’ reactants PROMOTE (positive feedback)
- products ‘INHIBIT’ conversion (negative feedback)
- metabolism is compartmentalized and different tissues metabolism interacts.
- Fed and fasting states involve interaction between different key tissues
