Post-absorption Processing of Carbohydrates Flashcards
Which 3 sugars are absorbed from the GI tract?
- glucose
- galactose
- fructose
Where do glucose and fructose come from?
Glucose comes from starch and glycogen breakdown (animal products)
Fructose comes from sucrose (sugar)
Where does galactose come from?
Galactose is one of the monomers of lactose
Lactose comes from dairy products
Which metabolic pathway will fructose and galactose enter?
They are converted to compounds that will enter the same metabolic pathway as glucose
What are the 2 potential products with galactose and fructose metabolism?
How common are they?
- hereditary fructose intolerance occurs in 1 in 20,000 births
- galactosaemia occurs in 1 in 23,000 births
They are genetically inherited and are associated with an absence of enzymes
What are the 4 possible fates of glucose?
- metabolism to produce energy (ATP)
- conversion to glycogen for storage
- synthesis of other cellular components
- conversion to fat for storage
What are the other cellular components that glucose may be converted to?
It can be converted into ribose phosphate, which is used to make DNA and RNA
It can be converted into glycoproteins and glycolipids
Where will glucose be stored as glycogen after a meal?
In the liver and skeletal muscle
Some glucose is also stored as fat
At what concentration should blood glucose be maintained at and why?
Maintaining blood glucose at around 5 mM is crucial for survival
This is because the brain relies on glucose for ATP synthesis
What happens if blood glucose falls below 3 mM?
This leads to confusion and coma
What happens if blood glucose rises above 8 mM?
Why does this occur?
It leads to long term vascular damage
Damage to the vascular system occurs through protein glycation
What must glucose be converted to before it can be used to produce energy?
Glucose and fatty acids are converted to acetyl CoA
Glucose must be first converted to pyruvate, then acetyl CoA
What happens once glucose (and fatty acids) are converted to acetyl CoA?
- Acetyl CoA enters the Krebs cycle
- The Krebs cycle produces reduced coenzymes (e.g. NADH)
- NADH carries high energy electrons to the IMM and passes them to the electron transport chain
Why is glucose a universal metabolic fuel?
It is used by all cells
Where does glycolysis take place?
What is significant about when glycolysis can generate ATP?
It takes place in the cytosol of ALL cells
Glycolysis can generate ATP in the presence or absence of oxygen
What are the 2 phases of glycolysis?
- preparative phase
2. generating phase
What does the preparative phase require?
Where does it run to?
It requires ATP
It runs from glucose to the generation of fructose 1,6-bisphosphate
Where does the generating phase run to?
What does it generate?
It runs from fructose 1,6-bisphosphate to pyruvate
It generates ATP and NADH
What is the overall equation for glycolysis?
glucose + 2 ADP + 2 Pi + 2 ATP + 2 NAD+
————>
2 pyruvate + 2 NADH + 4ATP + 2 H+ + 2 H2O
How many molecules of ATP are produced per molecule of glucose during glycolysis?
4 molecules of ATP are generated per glucose molecule
2 ATP are consumed during the preparative phase
The net production is 2 ATP
Under anaerobic conditions, how much ATP is generated per glucose molecule?
What is this process?
2 molecules of ATP are generated per molecule of glucose via glycolysis
This process is substrate level phosphorylation
Under aerobic conditions, how many molecules of ATP are generated per glucose and why?
Under aerobic conditions, ATP is used to generate a further 3-5 molecules of ATP through oxidative phosphorylation
Aerobic glycolysis generates 5-7 ATP molecules per glucose molecule
How many molecules of ATP are produced per glucose molecule after complete oxidation of glucose via the Krebs cycle?
This yields 30 - 32 molecules of ATP per glucose molecule
What is the first reaction in glycolysis which requires ATP?
Why is this reaction important?
Conversion of glucose to glucose-6-phosphate
This involves hexokinase and glucokinase
It prevents glucose from leaving the cell
What is the second reaction in glycolysis which requires ATP?
Which enzymes are involved?
Conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
This involves phosphofructokinase-1
What is significant about the ATP-requiring reactions in glycolysis?
Most reactions in glycolysis are reversible
These reactions are IRREVERSIBLE so allow for control of the pathway
What are the 3 key control points in glycolysis?
- Hexokinase/glucose
- Phosphofructokinase-1
- Pyruvate kinase
Why does the hexokinase/glucose stage act as a control point in glycolysis?
It converts glucose to glucose-6-phosphate so it is only performed when it is needed
Why is phosphofructokinase-1 the main control step of glycolysis?
It involves splitting a 6 carbon molecule into 2 3-carbon units
This is the start of the generating phase
Why does the generating phase run twice per molecule of glucose?
Each 3 carbon unit produced by phosphofructokinase enters the generating phase
Per glucose molecule, 2 3C units are produced
What is involved in the pyruvate kinase control step?
This converts phosphoenolpyruvate into pyruvate
It generates 1 ATP
What is the other reaction in the generating phase that generates a molecule of ATP?
Conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate
This is catalysed by phosphoglycerate kinase
What happens to pyruvate in the absence of oxygen?
It is NOT converted to acetyl CoA to enter the Krebs cycle
It is converted to lactate and NAD+ is regenerated
During the process of converting pyruvate to lactate, how much ATP is produced?
2 molecules of ATP are produced per molecule of glucose
Why is the conversion of pyruvate to lactate important for maintaining the rate of glycolysis?
It prevents the build-up of pyruvate at the end of the metabolic pathway by removing it
Build-up of pyruvate would slow down glycolysis
Why is the conversion of pyruvate to lactate important in maintaining NAD+ levels?
There is a requirement to regenerate NAD+
If NADH builds up, NAD+ levels fall
This also leads to a slowing down of glycolysis
What is meant by the Warburg effect?
High lactate production under aerobic conditions can be diagnostic of cancer
What type of glycolysis is used by tumour cells?
Tumour cells absorb glucose more rapidly than normal cells
They use anaerobic glycolysis in preference to oxidative phosphorylation, even in the presence of oxygen
Why do tumour cells use anaerobic glycolysis?
It aids the growth of the tumour in the absence of a good blood supply
As the tumour grows, it outstrips its own blood supply and it takes time for new blood vessels to grow
What type of scan can be used to identify tumours?
How does this work?
Positron emission tomography (PET) scans using 2-18F-deoxyglucose
It does this by identifying the increased glucose uptake and glycolysis of the tumour
What can glucose be converted into for storage?
- glycogen
2. fatty acids which are then converted into lipids
Where is glycogen found in the body?
Every cell contains a small amount of glycogen
It is mainly found in the liver and skeletal muscle
What is the structure of glycogen and what types of linkages does it contain?
It has a branched structure
a-1,4 linkages form the main body of the molecule
a-1,6 linkages form the branch points
Why is the branched structure of glycogen beneficial?
The branched effect allows glucose to be rapidly added to glycogen, and rapidly released when it is needed
What is the role of glycogen within the liver?
How does it achieve this?
The role of glycogen is to maintain blood glucose levels
Glycogen is broken down in the liver to release glucose into the bloodstream
How do glycogen levels in the liver fluctuate?
Glycogen levels fluctuate a lot
Liver glycogen levels are particularly low in the morning before food is consumed - this can lead to fainting
What is the first stage in glycogen synthesis?
What enzyme is required?
glucose-6-phosphate is converted to glucose-1-phosphate
This is performed by phosphoglucomutase
What happens to the glucose-1-phosphate that is formed in glycogen synthesis?
UTP and glucose-1-phosphate come together to form UDP-glucose and phosphate
UDP acts as a carrier
What is the role of UDP in glycogen synthesis?
UDP transfers glucose-1-phosphate to glycogenin
Glycogenin attaches to the hydroxyl group of a tyrosine residue
What factor limits the amount of glycogen that can be stored?
The amount of glycogenin present limits storage of glycogen
What happens once glucose-1-phosphate has joined to glycogenin?
The glycogen chain is elongated and branch points are added
The key control enzyme is glycogen synthase
What is glycogenolysis?
The breakdown of glycogen
What is the enzyme involved in the first stage of glycogenolysis?
What does it do?
Glycogen phosphorylase removes glucose units from glycogen
The glucose-1-phosphate is then converted to glucose-6-phosphate
Where will the glucose-6-phosphate be converted to glucose during glycogenolysis?
The glucose-6-phosphate is only converted to glucose in the liver and kidneys
This is due to the presence of the necessary enzyme
What happens to the glucose-6-phosphate produced in glycogenolysis in muscles?
In muscle cells, the glucose-6-phosphate goes straight into glycolysis
What are the 2 main effects of athletic training on muscles?
- increased numbers of mitochondria allow for more aerobic respiration
- increased muscle glycogen content
What type of energy do long-distance runners rely on?
What is “glycogen loading”?
They rely on fat metabolism for energy, but the ‘final push’ at the end requires glycogen
“glycogen loading” involves eating high carbohydrate diets in preparation for racing to increase glycogen stores
Why do long distance runners often collapse?
Exhaustion and collapse are caused by the depletion of glycogen
The muscles have run out of energy
What happens once glycogen storage is saturated?
Glucose can be broken down into acetyl CoA, which is converted to fatty acids
What will fatty acids be converted to for storage?
Fatty acids are converted to triacylglycerols for storage
In which cells does fatty acid synthesis occur?
It occurs in the cell cytosol of:
- mainly in the liver
- in adipose tissue
- in breast tissue during lactation
What happens to acetyl CoA produced from glucose?
It cannot get out of the mitochondria
High levels of acetyl CoA in the mitochondria leads to the synthesis of citrate
What happens to citrate that is formed when there are high levels of acetyl CoA in the mitochondria?
- Acetyl CoA carboxylase adds carbon dioxide to citrate
This produces malonyl CoA (3C molecule)
- This reaction is repeated many times, adding 2 carbons each time, until palmitate is produced
What is palmitate?
What happens once palmitate is formed?
Palmitate is a 16 carbon molecule
From palmitate, double bonds can be inserted into the chain and longer-chain fatty acids can be made
How can weight be gained from a low-fat diet?
If more sugar is taken in than required, this leads to the synthesis of fat
This process results in palmitate and longer chain fatty acids
Where does triacylglycerol synthesis occur?
What is involved in this process?
Occurs in the endoplasmic reticulum
This involves the addition of 3 fatty acids to a molecule of glycerol-3-phosphate
Where are triacylglycerols stored?
What happens to triacylglycerols in the liver?
They are stored in the cytosol of adipose tissue
In the liver, they are packaged to form VLDL, which is secreted into the blood
Where are the VLDLs produced in the liver transported to?
- adipose tissue for storage
2. other peripheral tissues for use as an energy source
What are the 2 main reasons why control of metabolism is needed?
It is needed to ensure that cells and the whole body can:
- work efficiently to utilise the materials it has to create the metabolites it needs
- adapt to different conditions
How does control of metabolism occur within the cell?
Cells respond to energy availability and the need for specific metabolites
How does control of metabolism occur on a whole body level?
hormonal signalling allows the body to adapt to the environment
What is meant by product inhibition as a way of controlling reaction rates?
If an enzyme is producing a lot of a product which is not being used, this will slow the reaction rate
How may covalent modification affect reaction rate?
Covalent modification can activate or inhibit an enzyme through the addition or removal of phosphate groups
How may hormones affect reaction rate?
Some hormones control the amount of enzyme that is present through controlling the rate of synthesis or degradation
Why are ATP levels not used to monitor energy status/
What is used instead?
ATP levels fluctuate quite quickly as it is constantly being produced and broken down
Levels of AMP are a sensitive monitor of energy status
What is the role of AMP-activated protein kinase?
It phosphorylates key enzymes involved in energy metabolism in the heart, adipose tissue, liver and muscle
What are the overall effects of AMP-activated protein kinase?
- it increases energy-providing pathways
2. it inhibits anabolic/synthetic pathways
What happens to levels of insulin after eating?
What is the result of this?
Levels of insulin are raised after eating
Transporters for glucose are moved into the membrane of the muscle, allowing more glucose to enter the cell
What will hexokinase be inhibited by?
It is inhibited by product inhibition
The retention of glucose-6-phosphate inhibits hexokinase
What controls the rate of glycogen synthesis and break down?
Phosphorylation
Phosphorylating glycogen phosphorylase speeds up glycogen breakdown
Phosphorylating glycogen synthase slows it down so there is less glycogen synthesis
What does high glucagon levels lead to?
high glycogen means that blood glucose levels are low
this leads to the breakdown of glycogen to release glucose
Why will high ATP inhibit the breakdown of glucose?
It signals that no more ATP is needed
How do energy levels influence the synthesis of fatty acids from glucose?
Low energy levels inhibit fatty acid synthesis from glucose
This is activated by the presence of insulin
When there is lots of food, excess energy will be stored
what is the role of insulin?
- increases expression of genes which code for enzymes of glycolysis
- decreases expression of genes which code for enzymes of gluconeogenesis
What is gluconeogenesis?
The process of making new glucose
What will high levels of insulin stimulate?
Glycolysis
What is signalled by high levels of glucagon?
A lack of energy
What is the role of glucagon?
It regulates the level of fructose-2,6-bisphosphate
This will activate glycolysis and inhibit gluconeogenesis
What happens when glucagon levels are high?
High glucagon will phosphorylate an enzyme, leading to degradation of fructose-2,6-bisphosphate
This decreases glycolysis
What happens when glucagon levels are low?
Low glucagon dephosphorylates an enzyme, leading to synthesis of fructose-2,6-bisphosphate
This increases glycolysis
