Week 3 (carbohydrate metabolism) Flashcards
What is metabolism?
The chemical processes that occur in living organisms, resulting in growth, production of energy, and elimination of waster.
Define catabolism
The break down of complex molecules, releasing energy
Define synthesis (anabolism)
Formation of complex molecules from simple starting materials
What are metabolic pathways?
A series of reactions connected together.
What is direction and speed of a pathway determined by?
The relative concentrations of each substrate.
Enzymes
Explain the rate limiting step in metabolic pathways
The rate limiting step controls how quickly the initial substrate is converted into the end product. The slowest step determines the speed of all reactions in the pathway.
What is Gibbs free energy and state its equation
Is a measure of available chemical energy.
G = H - TS
H: enthalpy (heat content)
T: temperature (Kelvins)
S: entropy (heat loss)
What type of reaction will be:
1. spontaneous
2. not spontaneous
- exergonic
- endergonic
Describe enzymes
Protein
Catalyse reactions in metabolism
Very specific
Act as control points in metabolism
What is enzyme action affected by?
Substrate concentration
Enzyme activity and concentration
Inhibition
Co-enzymes and co-factors
What do enzymes have binding sites for?
Substrate
Co-enzymes
Co-factors
Inhibitors
Explain competitive inhibitors
Prevent the substrate from binding
Competes for active site
Explain non-competitive inhibitors
Does not prevent substrate binding
Alters shape of enzyme
Explain allosteric enzymes
Usually contain 2 or more subunits.
Binding of the substrate alters the shape of enzyme.
Substrate binding increases the affinity for further substrates.
What does the first part of an enzymes name represent?
Substrate
What does the second part of an enzymes name represent?
Reaction
List the actions of enzymes and explain what happens
Kinase: add/removes phosphate group.
Dehydrogenase: removed H (oxidisation)
Decarboxylase: add/remove carboxyl group
Isomerase/mutase: rearranges (forms isomers)
Transferase: transfers functional groups
Hydrolase/lipase: adds water (hydrolysis)
Explain the role of enzymes in reversible reactions
The reactions in both directions is catalysed by the same enzyme.
Explain the role of enzymes in irreversible reactions
The reaction in each direction will be catalysed by different enzymes.
What is energy needed for in the body?
Synthesis of complex molecule
Active transport of molecules and ions
Muscular contraction
Cellular movement
What is ATP?
The energy currency of the body
What happens to ATP in anabolism/synthesis?
It is used up
What happens to ATP in catabolism?
Produces ATP
What happens to carbohydrates. lipids and alcohol during metabolism?
Broken down or stored for energy
Synthesis of body molecules
What happens to proteins during metabolism?
Synthesis of body molecules
Can be used for energy
What happens to minerals in metabolism?
Act as co-factors
Important for nervous and muscle action
What happens to vitamins during metabolism?
Act as co-enzymes and antioxidants
Name the key carbohydrates that are supplied in the diet
Monosaccharides
Disaccharides
Polysaccharides
Name the 4 monosaccharides that naturally occur in food
Glucose
Fructose
Galactose
Ribose
Name the 3 disaccharides and state what monosaccharides they are made from
Sucrose = glucose +fructose
Maltose = glucose + glucose
Lactose = glucose + galactose
Name and explain the two polysaccharides that make up starch
Amylose (15-30%): long, largely unbranched chains of D-glucose.
Amylopectin (70-85%): branched chains of D-glucose.
What is glycogen?
Mammalian storage polysaccharide of glucose.
What is cellulose?
The main polysaccharide found in plant cell walls.
A non-starch polysaccharide.
Major component of dietary fibre.
Individual chains are bound to each other through hydrogen bonding to form cellulose microfibrils.
Provide strength to cell walls in all directions.
What are non-starch polysaccharides?
Isomers of glucose joined together
What state is a carbohydrate in when it is absorbed?
Monosaccharide
What is carbohydrate metabolism actually representing?
Glucose metabolism
What is glycolysis?
The breakdown of glucose to liberate energy in the form of ATP.
Takes places in the cytosol.
1 6 carbon glucose is split into 2 3 carbon pyruvate.
Name the two stages of glycolysis
Investment stage (uses ATP)
Pay off stage (creates ATP)
Explain step 1 of glycolysis: phosphorylation of glucose
Irreversibly ‘traps’ glucose in the cell.
Lowers (glucose) in the cell.
Highly thermodynamically favourable.
Uses ATP.
Under substrate level control.
Hexokinase
Explain step 2 of glycolysis: isomerisation of G-6-P
Changing toa pentagonal ketose allows easier further phosphorylation. Allows for creation of potentially symmetrical molecule.
Reversible
Direction and rate = under substrate level control.
Isomerisation of G-6-P.
Explain step 2 of glycolysis: phosphorylation of F-6-P
Irreversible
The committed step of glycolysis.
Uses ATP.
Requires magnesium as a cofactor.
Phosphofructokinase-1 (PFK-1) is a key enzyme of control.
ATP = powerful inhibitor.
Produces a ‘symmetrical’ molecule for splitting.
Explain step 4 of glycolysis: splitting
Reversible
Two halves are not quite the same = DHAP + GAP.
Need to have both halves in the form of GAP.
Aldolase
Explain step 5 of glycolysis: triose phosphate interconversion
Reversible
Allows for continual breakdown using one pathway.
End of the investment stage.
Triose phosphate isomerase.
Explain step 6 of glycolysis: oxidation of GAP
Reversible
First energy yielding step of glycolysis.
NAD+ to reduced to NADH.
Generates a high energy phosphate compound (1,3BisPG)
Allows for ATP production in subsequent steps.
Glyceraldehyde 3-phosphate dehydrogenase.
Explain step 7 of glycolysis: first ATP production
Reversible
Substrate level phosphorylation of ADP.
1,3 BisPG donates phosphate to form ATP.
Phosphoglycerate kinase.
Explain step 8 of glycolysis: rearrangement
Phosphoglucomutase
Reversible
Explain step 9 of glycolysis: dehydration
Enolase
Reversible
Releases water
Explain step 10 of glycolysis: second ATP production
Irreversible
Substrate level phosphorylation of ADP.
Loss of phosphate from PEP leads to tautomerisation which helps drive the reaction.
Pyruvate kinase (PK) requires magnesium as a co-factor.
PK = highly regulated enzyme
Describes hexokinase
Has allosteric enzyme kinetics.
Ensures glucose is only irreversibly entered into glycolysis at high glucose.
Ensures carbohydrate utilisation in muscle and adipose tissue influenced by glucose availability.
Describes glucokinase
Ensures utilisation of glucose even at low glucose.
Key for glucose uptake from portal system.
Key to regulating glucose metabolism and supply.
Give the chemical equation for glycolysis
Glucose + 2NAD+ + 2ADP + 2Pi –> 2 pyruvate + 2 NADH + 2ATP
What is the net gain of ATP during glycolysis?
2 ATP
What is anaerobic catabolism?
2 ATP can be generated per glucose, without oxygen but needs to recycle NAD+ used in the conversion of glyceraldehyde 3-phosphate to 1,3 Bisphosphoglycerate.
This is achieved by dehydration reaction forming lactate.
What is the chemical equation for anaerobic catabolism?
Glucose + 2Pi + 2ADP <–> 2 lactate + 2ATP + 2H2O
What is involved in the Cori cycle?
Lactate can be recycled back to glucose in the liver by gluconeogenesis.
Name the 3 key enzymes that are involved in irreversible reactions
Hexokinase
Phosphofructokinase (PFK-1)
Pyruvate kinase
What is enzyme activity controlled by?
Hormones
Other metabolites
What is phosphofructokinase?
The key enzyme in control of glycolysis
What is inhibition reversed by?
Insulin
AMP
Fructose 6-phosphate
Catecholamines (in muscle)
What is inhibition enhanced by?
Glucagon
Citrate
Catecholamines (in liver)
What is pyruvate kinase activated by?
Fructose 1,6 bisphosphate
Insulin (via counteracting glucagon)
What is pyruvate kinase inhibited by?
ATP
Glucagon
Alanine (signalling an abundance of building blocks)
What happens to pyruvate during:
1. anaerobic catabolism
2. aerobic catabolism
3. synthetic
4. gluconeogenic
- converted to lactate
- converted to acetyl CoA via the TCA cycle and oxidative phosphorylation.
- converted to alanine (amino acid)
- converted back to form glucose
What is PFK1 inhibited by?
ATP (energy availability)
What is the TCA cycle fed by?
The breakdown products of carbohydrates, lipids and proteins.
How is energy generated in the TCA cycle?
Through NADH, FADH2 and GTP
What is a by-product of the TCA cycle?
Carbon dioxide
What is pyruvate converted into?
Acetyl CoA
What is a MPC?
Mitochondrial pyruvate carrier
What does an NCP do?
Carries the pyruvate molecule through both the outer and inner mitochondrial membranes into the matrix, via facilitative diffusion.
Where does the TCA cycle occur?
Matrix of the mitochondria
Is the conversion of pyruvate into acetyl CoA an irreversible or reversible reaction?
Irreversible
A committal step in energy metabolism.
What 2 co-enzymes catalyse the conversion of pyruvate into acetyl CoA?
Pyruvate dehydrogenase
Riboflavin thiamin
What is acetyl CoA?
A 2 carbon skeleton derived from carbohydrates, fatty acids and amino acids.
It ‘feeds’ the TCA cycle.
Where does glycolysis and anaerobic catabolism of CHO happen?
In the cytosol
Describe the role of electron carriers in the TCA cycle
Act as proton and electron acceptors in reduction reactions.
Carry electrons to the respiratory chain.
Feed electrons to the respiratory chain.
Feeding electrons through the respiratory chain produces ATP.,
Name the steps of the TCA cycle
- Formation of citrate (entry of acetyl CoA)
- Formation of isocitrate
- Oxidation of isocitrate to a-ketoglutarate + carbon dioxide.
- Oxidation of alpha-ketoglutarate to succinyl CoA.
- Conversion of succinyl CoA to succinate.
- Oxidation of succinate to fumarate.
- Hydration of fumarate to malate.
- Oxidation of malate to oxaloacetate
What is the TCA cycle otherwise known as?
Krebs cycle
Citric acid cycle
What is oxidised during the TCA cycle?
Acetyl CoA to form carbon dioxide and water
What is reduced during the TCA cycle?
NAD+ and FAD+ pick up electrons and are reduced to NADH and FADH
How many molecules of acetyl CoA is produced in one revolution of the TCA cycle?
1
How many molecules of NADH are produced in one revolution of the TCA cycle?
3
How many molecules of FADH is produced in one revolution of the TCA cycle?
1
How many molecules of GTP are produced in one revolution of the TCA cycle?
1
How is the TCA cycle controlled?
The rate of the TCA cycle is adjusted to meet ATP demand, which is dependent on supply of acetyl CoA and the availability of NAD+ and FAD+.
It is specifically controlled by 3 irreversible reactions: citrate synthesis, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.
What happens during anaplerotic reactions?
Constant levels of TCA intermediates are maintained
What happens during cataplerotic reactions?
Utilisation of TCA intermediates for biosynthetic pathways.
How can oxaloacetate be regenerated?
Can be formed directly from pyruvate, by the enzyme pyruvate carboxylase.
Why is the regeneration of oxaloacetate important?
It keeps the TCA cycle operating when amino acids are synthesises.
It is an important step in gluconeogenesis.
What is the control of the TCA cycle dependent on?
The supply of acetyl CoA, NAD+ and FAD+.
Name the types of metabolism where the TCA cycle is a common pathway
CHO metabolism
Lipid metabolism
Alcohol metabolism
Amino acids metabolism
Ketone oxidation
