Define cell metabolism
The highly integrated network of chemical reactions that occur within the cells
In which states are physiological changes to blood concentration of cell nutrients and their waste products seen?
- After meals
In which states are pathological changes to blood concentration of cell nutrients and their waste products seen?
- Certain enzyme deficiency states
Where do cell nutrients circulating in the blood come from?
- The diet
- Synthesis in body tissue from precursors (not essential fatty acids or amino acids)
- Released from storage in body tissue
Cell nutrients undergo various chemical transformations in body tissues. What are they?
- Degradation to release energy - all tissues -
- Synthesis of cell components - all tissues except mature RBCs
- Storage - Liver, adipose tissue, skeletal muscle - Interconversion to other nutrients - Liver, adipose tissue, kidney cortex
- Excretion - Liver, kidney, lungs
What is oxidation?
Addition of oxygen or removal of a hydrogen ion
Loss of electron
What is reduction?
Removal of oxygen or addition of hydrogen ion
Gain of electron
What are the major carrier molecules in their oxidised states?
What are the major carrier molecules in their reduced states?
NADH + H+
NADPH + H+
Does exergonic or endogenic reactions occur spontaneously?
ATP acts as a _____ of free energy, not a ______
List high energy signals
ATP NADH, NADPH and FAD2H
List low energy signals
ADP NAD+, NADP+ and FAD
Describe CNS metabolism
- Energy from glucose (also ketone bodies under certain conditions)
- No fuel storage, therefore requires continuous supply of feels and oxygen
Describe heart muscle metabolism
- Energy from glucose, lactate, fatty acids or ketone bodies
- No fuel storage, therefore requires continuous supply of fuels and oxygen
Describe skeletal muscle metabolism
- Energy from glucose, fatty acids or ketone bodies
- Stores glucose as glycogen and some triacylglycerol
- Muscle protein can be used in emergency
- Can oxidise glucose to lactate under anaerobic conditions
Describe liver metabolism
- Energy from fatty acids, amino acids or alcohol. Can use galactose and fructose
- Stores glucose as glycogen
- Makes glucose from lactate, glycerol and amino acids
- Makes ketone bodies, cholesterol and triacylglycerol
Describe adipose tissue metabolism
- Energy from glucose or fatty acids
- Stores fuel in the form of triacylglycerol
Outline why cardiac arrest affects the heart and central nervous system more rapidly than it affects skeletal muscle
- Cardiac muscle and CNS are highly specialised tissue and do not contain significant stores of fuel or oxygen
- They have limited capacity for anaerobic metabolism
- Skeletal muscle has significant stores of fuel (glycogen) and oxygen (myoglobin)
- Skeletal muscle has limited capacity for anaerobic metabolism (~5minutes)
Why can humans digest glycogen but not cellulose?
- Humans do not produce an enzyme that can break 1-4β linkages (found in cellulose)
- We can degrade glycogen as we produce enzymes that degrade 1-4α and 1-6α linkages
Under anaerobic conditions, pyruvate produced by glycolysis in skeletal muscle may be reduced to lactate. What advantage is this to muscle cells?
- There is a fixed amount of NAD+ and NADH in the cell - The reactions of glycolysis requires presence of NAD+
- If all NAD+ is converted to NADH, glycolysis will stop due to lack of NAD+
- This does not normally happen under aerobic conditions
- NADH is converted back to NAD+ by the electron transport chain - Under anaerobic conditions, pyruvate is converted to lactate via the enzyme lactic dehydrogenase using NADH which is oxidised to NAD+
- This allows glycolysis to continue so it can provide the cell with ATP via substrate level phosphorylation
What are the possible fates of lactate produced by skeletal muscle under anaerobic conditions?
- Lactate released from muscle cells and then carried to the liver and heart muscle
- In both tissues it is converted to pyruvate by lactic dehydrogenase
- In heart muscle pyruvate is converted to acetyl-CoA that is subsequently oxidised in the TCA Cycle to provide energy
In the liver 3 things can occur
1) May also be oxidised to provide energy
2) Most will be converted to glucose via the gluconeogenic pathway
3) Oxidation to acetyl CoA which may be used for lipid biosynthesis (fatty acids, ketone bodies or cholesterol)
Define lactic acidosis
An elevation of plasma lactate that affects the buffering capacity of the plasma
Monosaccharide units are linked by _______ ________ and loss of ______ to form polysaccharides
Glycogen contains ______ and _______ bonds linking glucose molecule together
1-4α and 1-6α
What breaks down dietary polysaccharides?
- Hydrolysed by glycosidases
- This releases glucose, maltose and smaller polysaccharides (dextrin)
Where is the major site of fructose and galactose metabolism?
What steps are irreversible in glycolysis and what enzymes catalyse them?
1 - Hexokinase (glucokinase in some tissue such as the liver and brain)
3 - Phosphofuctokinase
10 - Pyruvate Kinase
Outline the key features of glycolysis
- Consists of 10 enzyme-catalysed steps that occur in the cell cytoplasm
- Active in all cells
- NADH produced from NAD+
- There is no loss of carbon dioxide
- Only pathway to generate ATP anaerobically
- Net gain of 2 ATP
Where does glycolysis occur?
Explain how blood concentration of lactate is controlled
- Normally the amount of lactate produced = the amount of lactate utilised, normally 1mM
- The concentration can increase under certain conditions E.g Strenuous Exercise
- When 5mM is reached, it surpasses the renal threshold and it begins to affect the buffering capacity of the plasma causing lactic acidosis
Outline lactose intolerance
- Low activity of the enzyme lactase
- Unhydrolysed lactose is fermented by gut bacteria to form various organic acids that irritate the GI tract
In Galactosaemia, individuals are unable to utilise galactose obtained from the diet because a lack of _____ OR _________ ________ ____ _______
Galactose 1-phosphate uridyl transferase
Which of galactokinase or galactose 1-phosphate uridyl transferase deficiency is more severe?
Galactose 1-phosphate uridyl transferase
Leads to accumulation of galactose and galactose 1-phosphate (which is toxic to the liver) accumulates in the tissue
Only galactose accumulate in the rarer galactokinase deficiency
Outline the effects of galactose accumulation
- Accumulation leads to its reduction to galactitol by the activity of the enzyme aldose reductase
- This reaction depletes NADPH
- Leads to cross-linking of lens proteins by disulphide bonds - cataracts
- Glycation of lens proteins due to high levels of galactose
- Increased galactose + galactitol leads to raised into-occular pressure (glaucoma), if untreated = blindness
- Accumulation of galactose 1-phosphate in tissue leads to damage to the liver. kidney and brain
Name the three most common types of monosaccharide
Triose, pentose and hexose
Name the two types of hexose monosaccharide
Aldose and ketose
In what isomer form are monosaccharide found?
Name the three most common types of polysaccharide
Starch, glycogen and cellulose
What are dextrins?
Small polysaccharides produces during initial stages of digestion
Where does the digestion of carbohydrates begin and where does it continue next?
- Mouth with the release of salivary amylase
- Continues in the duodenum with the release of pancreatic amylase and then the jejunum
Where are glycosidase enzymes located?
Glycoprotein complexes on the brush border membranes of epithelial cells in the duodenum and jejunum
What are the main glycosidase enzymes involved in carbohydrate digestion?
Lactase, glycoamylase and sucrase
Which body tissues are glucose dependent?
Kidney, lens of the eye, CNS and RBCs
Which enzyme, hexokinase of glucokinase, has a higher affinity for glucose?
Hexokinase is found in the skeletal muscle where there is a lower glucose concentration and increased glucose requirement resulting in higher affinity. Glucokinase is found in the liver and so has a lower affinity for glucose as there is higher availability
What are the products of glycolysis
Net 2 ATP, 2 Pyruvate, 2 NADPH, 2 H+ and 2H20 (water)
Name two important intermediates in glycolysis
2,3-bisphosphoglycerate and Dihydroxyacetone phosphate (DHAP)
2,3-bisphosphoglycerate is an intermediate produced in glycolysis. Why is it important?
Allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin, thus enhancing the ability of RBCs to release oxygen near tissues that need it most. 2,3-BPG is thus an allosteric effector
Glycerol phosphate (from DHAP) is an intermediate produced in glycolysis. Why is it important?
Involved in triglyceride synthesis
What are the symptoms of lactose intolerance?
Bloating - production of carbon dioxide and methane by colonic bacteria
Diarrhoea - increased osmotic pressure due to lactose build up in lumen of colon