Session 2: Energy Production (Carbohydrates) Flashcards
What is the general formula for carbohydrates?
(CH2O)n
What are the functions of carbohydrates? (5)
- Energy production
- Energy storage
- Building macromolecules
- Dietary fibres
- Sparring use of proteins for energy
Why are cells within RBCs and the lens of the eye dependent on glycolysis?
They lack mitochondria so unable to synthesise ATP through metabolic reactions so must rely on glucose (and the process of glycolysis) to generate ATP since glycolysis occurs in the cytosol rather than mitochondria
Where in the cell does glycolysis occur?
Cytosol of all tissue
Why are cells within neutrophils and innermost cells of the kidney medulla dependent on glucose?
They are within low O2 environment so they are unable to use mitochondria to synthesise ATP so must rely on glycolysis to produce ATP as it does not require O2 to synthesise ATP
What is sucrose?
Disaccharide made up of glucose and fructose
What is lactose?
Disaccharide made up of glucose and galactose
What is maltose?
Disaccharide made up of glucose and glucose
What is starch?
A carbohydrate storage molecule in plants, it is a polymer of glucose
What is glucagon?
A carbohydrate storage molecule in animals, it is a polymer of glucose
Why is cellulose (β1-4 bonds) not digested? What does it become instead?
The body doesn’t produce enzymes to break down the β1-4 bonds => forms a major component of dietary fibre
Which glucose transporter is regulated by insulin?
GLUT 4 - it is responsible for insulin-regulated glucose intake
Which enzymes are key in glycolysis?
Hexokinase (glucokinase in liver) & phosphofructokinase-1
What is the net synthesis of ATP to glucose molecules and why?
Net total is 2 ATP per glucose
4 ATP molecules produced per glucose molecule but 2 ATP is required for investment phase of glycolysis so 4ATP-2ATP = 2ATP per glucose
What are the key features of glycolysis (7)?
- Occurs in cystole of all tissues
- Irreversible
- Exergonic and oxidative
- Central pathway of carbohydrate catabolism
- Does not require oxygen to produce ATP
- Provides biosynthetic precursors for FA, AA and nucleotides
- 2 molecules of NADH produced per glucose molecule
What does the phosphorylation of glucose (glucose to glucose-6-phosphate) cause?
Glucose becomes negatively charged and so cannot go back across the plasma membrane - commits glucose to metabolism
Why are there so many steps to glycolysis?
- Efficient energy conservation
- Can be controlled more easily
- Gives versatility
Where is 2,3-Bisphosphoglycerate produced and why is it an important intermediate?
Produced in RBCs
Regulator of haemoglobin-O2 affinity (facilitates supply of oxygen to tissues by binding to haemoglobin)
Where is glycerol phosphate produced and why is it an important intermediate (function)?
Produced in adipose tissue and liver
Important for triglyceride and phospholipid biosynthesis
Why is glucose phosphate important for lipid synthesis in adipose tissue?
Lipid synthesis requires glycolysis
What is metabolism?
Set of processes which derive energy and raw materials from diet and use them to support repair, growth and activity of the body to sustain life.
Describe catabolic pathways.
Breakdown larger molecules into smaller ones (intermediary metabolites)
Release a lot of free energy
Oxidative - releases H atoms - reducing power
Describe anabolic pathways.
Synthesise of larger molecules from intermediary metabolites
Use energy released from catabolism (ATP)
Reductive - use H released in catabolism
Why do some organic precursors feedback in metabolism pathways?
To form more building block material
Why can humans not use heat energy for work?
Because humans are isothermal
What is an exergonic reaction?
Exergonic - release energy
Only reactions that occur spontaneously
-ve ∆ G => energy is released so products have low energy
What is an endergonic reaction?
Reaction that requires energy, energy is put in do +ve ∆ G
How are chemical bond energy of fuel molecules released?
By oxidation reactions
What are the function of H-carrier molecules/co-enzymes/co-factors and what are they synthesised from?
Act as carriers for reducing power for ATP production (NADH + H+, FADH2) and biosynthesis (NADPH)
When fuel molecules are oxidised, electrons and protons are transferred to carrier molecules
Synthesised from vitamins
How are H-carrier/co-enzymes/co-factors molecules converted to their reduced forms?
By adding two H atoms (H+ + e-)
How does the absence of galactose-1-P- uridyl transferase affect glycolysis?
Converts galactose-1-P to glucose-1-P for glycolysis so absence would reduce rate of glycolysis
Which is more problematic in galactosaemia, transferase deficiency or galactokinase deficiency?
Transferase because the build up of galactose-1-P is very damaging
What tissue is responsible for the major part of galactose metabolism?
Liver
What 3 enzymes are involved in the initial stages of galactose metabolism?
Galactokinase
Galactose-1-P uridyl transferase
UDP-galactose 4’ - epimerase
How would you determine which enzyme is missing or defective in a patient with galactosaemia?
Enzyme assay
What is galactitol and how is it formed?
Reduced alcohol form of galactose. Forms when galactose is not metabolised properly so it enters different pathways
Why is the pentose phosphate pathway an important metabolic pathway in some tissues?
Produces NADPH required for:
maintenance of GSH levels, fatty acid biosynthesis, steroid synthesis & detoxification reactions
Produces C5-sugar ribose required for the synthesis of:
Nucleotides and DNA & RNA
Why do galactosaemic patients develop cataracts?
- Increased build-up of galactose within the lens triggers an increase in aldose reductase activity to convert galactose to galactitol.
- Lens membranes are semipermeable.
- Galactitol accumulation creates a hypertonic condition
- Water is drawn into the lens causing swelling & damage to the lens
How do low levels of NADPH affect RBCs
Low levels of NADH means that low levels of GSH which protects cells from oxidative stress
disulphide bonds form between haemoglobin & other proteins -> insoluble aggregated proteins (Heinz bodies) -> haemolysis
Can RBCs get NADH from other pathways?
No only from pentose phosphate pathway
What is the rate-limiting factor in the pentose phosphate pathway?
glucose 6-phosphate dehydrogenase
Describe the features of the pentose phosphate pathway (5).
- starts from glucose-6-phosphate
- important source of NADPH
- produces C5-sugar ribose
- no ATP synthesised, CO2 produced
- rate-limiting enzyme glucose 6-phosphate dehydrogenase
What is the difference between essential fructosuria and fructose intolerance?
in essential fructosuria, fructokinase is missing causing a build-up of fructose
in fructose intolerance, aldolase is missing causing build-up of fructose-1-P => leads to liver damage & death
How is fructose intolerance managed?
Fructose & sucrose are removed from diet
How is glycolysis continued when there is a requirement for NAD+?
Lactate dehydrogenase occurs to regenerate NAD+
Pyruvate is reduced to lactate
NAD+ is regenerated and so glycolysis proceeds & ATP can be synthesised
Why do some cells need lactate dehydrogenase to occur?
- some cells eg (RBCs & eye lens) have no mitochondria so cannot undergo stage 3 or 4 metabolism
- Stage 4 metabolism needs O2 which may be insufficient (eg in anaerobic conditions - exercising skeletal muscles)
so glycolysis proceeds & ATP can be synthesised & cells can continue to function
How many moles of NADH are produce per mole of glucose in glycolysis?
2
Where is NAD+ usually regenerated from?
NADH
What is lactate produced from? How?
glucose & alanine produce pyruvate which is reduced to lactate by lactate dehydrogenase
- w/o major exercise (40-50g/24hrs)
- strenuous exercise (30g/5min)
- pathological situations eg shock, congestive heart disease
What is lactic acidosis?
plasma lactate above 5mM
above renal threshold
blood pH lowered => causes proteins to denature causing altering protein function
What is hyperlactatemia?
plasma lactate 2-5mM
below renal threshold
no change in blood pH (buffering capacity)
What is plasma lactate concentration determined by?
- rate of production
- rate of utilisation by tissue eg liver, heart, muscle
- rate of disposal = lactate levels really high = begin to be cleared by kidney (excreted)
What happens if there is a higher rate of production but lower rates of utilisation & disposal
hyperlactatemia
Which enzymes regulate glycolysis?
hexokinase & phosphofructokinase (PFK)
How does phosphofructokinase (PFK) work?
using ATP converts fructose-6-phosphate to fructose-1,6-bisphosphate
How is phosphofructokinase (PFK) stimulated?
stimulated by high AMP & high F2,6,BP (low energy signals)
How is phosphofructokinase (PFK) inhibited?
inhibited by high ATP & high citrate (high energy signals)
What actually regulates the activity of enzymes? (muscle & hormonal ratio)
the ratio of AMP:ATP
the ratio of insulin:glucagon
What type of feedback is used in PFK enzyme regulation? Explain how it works.
Negative feedback
ATP = inhibitor => high ATP = inhibit & return to normal so could stimulate AMP (?)
AMP = stimulator
How does hexokinase work?
catalyses the phosphorylation of glucose which helps to prepare the compound for cleavage in a later step.
