What form is glucose stored as?
Glycogen
Where are the major sites of storage for glycogen?
Liver and skeletal muscle
What is the difference between glycogen that is released by the liver compared to by the skeletal muscles?
Skeletal muscle tends to keep the the glucose for itself whereas the liver releases it into the bloodstream
Describe the structure of glycogen
A very large branched polymer of glucose and is formed mostly by alpha1,4-glycosodic bonds between glucose residues
What happens every 10 residues of glucose in glycogen?
There is an alpha1,6-glycosidic bonds which causes a branching point
What makes glycogen pellets soluble in the cell cytoplasm?
The OH groups
Give an example of an enzyme that synthesises and degrades glycogen
Synthesis: glycogen synthase
Degradation: glycogen phosphorylase
What enables a molecule of glucose to be trapped in the cell for glycogen synthesis?
Phosphorylation by hexokinase or glucokinase to form glucose-6-phosphate
What is the role of phosphoglucomutase in glycogen synthesis?
To move the phosphate group from the 6 position to the 1 position, forming glucose-1-phosphate and making it committed to glycogen synthesis
What does glucose-1-phosphate react with in glycogen synthesis and what does it form?
UTP and forms UFP-glucose
Describe what happens in the formation of UDP-glucose
2 phosphate groups from UTP are removed and the glucose-1-phosphate group is added to the remaining molecule
How is a glucose unit from UDP-glucose added onto a glycogen chain of more than 4 units?
Glycogen synthase adds the glycosyl residue onto the OH group at the C4 terminus of glycogen to form a alpha1,4 glycosidic linkage and liberate UDP
What happens to UDP after is has been removed from the glycosyl unit in glycogen synthesis?
It is converted into UTP by nucleoside diphosphatase in the presence of ATP and can then be used again
What is the name of the bonds between each glucose unit in glycogen?
alpha1,4 glycosidic bonds
What is the name of the primer for glycogen synthesis?
Glycogenin
When is glycogenin required?
If the glycogen chain is not 4 units long
Describe the structure of glycogenin
A protein containing a short oligosaccharide of alpha1,4 glucose units attached to the phenolic oxygen atom of a tyrosine amino acid
Why is branching important in glycogen?
It increases the solubility of the glycogen pellet
It creates a large number of termini where lots of glycogen synthesis and degradation an occur
How long must the glycogen chain be in order for it to be cleaved by branching enzyme?
11 residues long
Describe the cleaving of a glycogen chain when it is branched
The branching enzyme cleaves the chain at leave 4 units from the start and reattaches it to the 6th position making it an alpha1,6 glycocidic link, glucose will continue to be added to the ends of both branches
What hormone is released by the pancreas to signal to the liver to breakdown glycogen into glucose units in the liver?
Glucagon
What cleaves glycogen molecules to individual glucose molecules?
Glycogen phosphorylase in the presence of orthophosphate (free phosphate groups)
What hormone is released to signal the breakdown of glycogen in the skeletal muscle?
Adrenaline released from adrenal glands
What is produced during the cleaving of a glycogen?
Glucose-1-phosphate and the glycogen residue
At what point does glycogen phosphorylase stop cleaving glycogen?
When it is 4 units away from a branch point
Describe the debranching process
4-alpha-glucotransferase transfers 3 units out of the 4 left of the branch and adds it onto the main stem, alpha1,6 glucosidase then hydrolyses the alpha1,6 bonds on the remaining glucose unit, releasing the glucose
What happens to the glucose-1-phosphates after they have been cleaved off?
Phosphoglucomutase converts it to glucose-6-phosphate
After glycogen degradation, what happens to the glucose-6-phopshate in the liver?
Glucose-6-phosphatase removes the phosphate group so that the glucose can diffuse out of the cell and into the blood
What happens to the glucose-6-phosphate after glycogen degradation in skeletal muscle?
It is converted into pyruvate and used in glycolysis in the Krebs cycle to generate ATP
What is Type 5 McArdle’s disease?
When a person doesn’t have glycogen phosphorylase in the muscle and therefore cannot break down glycogen to G-1-P leading to decreased energy production from TCA
What are the symptoms of Type 5 McArdle’s disease?
Muscle cramps and fatigue
What is Type VI McArdle’s disease and why is it more dangerous?
The patient doesn’t have glycogen phosphorylase in the liver causing the liver to enlarge due to increased glycogen, it causes hypoglycaemia. During fasting the body struggles to maintain blood glucose
What are the 3 requirements for fatty acid synthesis?
ATP for energy
NADPH as an electron donor
Acetyl-CoA for the carbon backbone of the fatty acid
Where is ATP generated for fatty acid synthesis?
In the mitochondria by oxidative phosphorylation which is transferred via a transporter to the cytosol
Where is the NADPH generated for fatty acid synthesis?
In the cytosol by the pentose phosphate pathway
Describe what happens in the pentose phosphate pathway
Glucose-6-phosphatte is converted to 6-phosphogluconolactone by G-6-P dehydrogenase and this reduces NADP to NADPH.
Where is the acetyl-CoA generated for fatty acid synthesis?
In the mitochondria by pyruvate dehydrogenase
How does the Acetyl-CoA cross the mitochondrial membrane to get into the cytosol
It forms citrate in the first step of the TCA cycle which can then cross the inner mitochondrial membrane using a tricarboxylic acid transporter. In the cytosol, ATP-citrate lyase then convers citrate into acetyl-CoA and oxaloacetate using 1 x ATP
How many carbon chains are in a fatty acid molecule in humans (palmitate)
16
Before condensation reactions in fatty acid synthesis, what must happen to the acety-CoA and how does this happen?
They must be activated by carboxylating it with HCO3- to malonyl-CoA which is catalysed by Acetyl-CoA Carboxylase, it uses 1 x ATP
What does acetyl-CoA carboxylase being a regulatory enzyme mean?
Its activity determines the rate of fatty acid synthesis
What types of reactions grow the the carbon chain on fatty acids?
Condensation
How many carbons is malonyl-CoA made from?
3
What is the name of the multifunctional enzyme that forms fatty acids from malonyl-CoA?
Fatty acid synthase
What is ACP?
Acyl carrier protein, it transports the growing chain of fatty acid between the enzymes that are used to grow the chain
What is phosphopantetheine?
A coenzyme attached to ACP which forms a covalent bond with acetyl CoA from the malonyl-CoA
What is the primer for the condensation reactions in fatty acid synthesis?
Acetyl-CoA
What is the overall role of Acetyl transcylase (AT)
To put the primer into the condensing enzyme (CE)
What is the condensing enzyme in fatty acid synthesis?
Acyl-malonyl-ACP condensing enzyme (CE)
What part of phosphopantetheine does the malonyl bind to in fatty acid synthesis?
The sulphur atom
What enzyme transfers malonyl to phosphopantetheine?
Malonyl transacylase (MT)
What happens in the condensation reaction between malonyl-ACP and the growing chain on the CE
The CO2 is removed from malonyl, the remaining 2 carbon units condense with the growing chain/ primer on the CE, the products detaches from CE and remains attached to ACP
After condensation in fatty acid synthesis, what occurs next and why?
A series of reduction reactions to remove double bonds so that the chain is saturated
Removal of C=O, and C=C
Which part of the condensing enzyme in fatty acid synthesis do substrates bind to?
Onto the cysteine sulphur
After the fatty acid chain reaches 16 carbons long what happens?
Thiosterase cleaves off the palmitate group from ACP and transfers it to CoA to make palmitoyl-CoA
Which part of fatty acid synthesis requires energy and in what form?
The reduction of C=O to C-OH, uses NADPH
What makes fatty acid synthase a multifunctional enzyme rather than a multienzyme complex?
It is a single polypeptide chain and so is one enzyme
Describe the structure of fatty acid synthase
It is a dimer containing 2 identical polypeptide chains, each with 3 domains, the chains are aligned next to each other but at opposite ends
How many fatty acids does fatty acid synthase make at once>
2
Why is it beneficial for fatty acid synthase to be a dimer and contain 2 identical polypeptide chains?
ACP can reach the different domains by making use of both chains rather than having to move from one end to the other, 2 fatty acids can be made at once
What are the benefits of being able to synthesise a molecule within a multifunctional enzyme?
Intermediates are directly transferred between each domain, there is no dilution of substrate in the cytosol, there is no loss of substrate, quicker process
Where is triacylglycerol synthesised?
In adipose tissue or in the liver where it is then transferred to adipose tissue or other tissues
What is the name of the multienzyme complex that synthesises triiacylglycerol
Triacylglycerol synthetase
Where is triacylglycerol synthetase found?
It is bound to the cytosol side of the E R membrane
What are the 3 enzymes that make up triacylglycerol synthetase and their ratio
1:1:1, glycerol-3-phosphate acyltransferase (GPAT), lysophosphatidate acyl transferase (LPAT), diacylglycerol acyl transferase (DGAT)
What is the glycerol molecule used in triacylglycerol synthesis?
Glycerol-3-phosphate
What is the best store of enegry?
Fatty acids
What are the cells in adipose tissue called that are used to store fat?
Adipocytes
Describe the structure of an adipocyte
A cell containing a triacylglycerol droplet surrounded by a thin strip of cytosol containing the nucleus
Where is fat synthesised?
In the cytosol and then passed to the droplet of triacylglycerol
What transports fat synthesised by the liver into the adipose tissue?
Lipoproteins
What happens in times of starvation to the triacylglycerol?
It is hydrolysed (lipolysis) to release free fatty acids into the blood to make energy for beta oxidation
What happens in terms of fat storage in people who are obese?
Their bodies store too much fat as triacylglycerol in adipose tissue
What is the equation for BMI?
Body weight (kg)/height^2 (m)
How is obesity prevented or cured?
By reducing food intake and increasing exercise
What is orlistat?
An oral drug that inhibits the gastric lipases (digest fat) and uptake of dietary fat
What is leptin?
A hormone released by adipose tissue and the stomach that signals to the hypothalamus when to eat and when to stop eating, scientists are trying to mimic this hormone in drugs to help people reduce their food intake