Flashcards in Metabolism Session 4 - Energy Storage Deck (76):
Describe the major energy stores in a 70kg man
Type of Fuel
Energy Content (kJ)
Where is glycogen stored, and in what quantities?
Stored in granules in
Liver – up to 100g
Skeletal muscle – up to 300g
Give the four reactions involved in glycogen synthesis, and the enzymes which catalyse them
1.Glucose + ATP --> Glucose 6-Phosphte + ADP (catalysed by hexokinase)
2.Glucose 6-Phosphate --> Glucose 1-Phosphate (catalysed by phosphoglucomutase)
3.Glucose 1-Phosphate + UTP + H2O --> UDP-Glucose + 2 Pi
4.Glycogen (n residues) + UDP-Glucose --> Glycogen (n+1 residues) + UDP
Glycogen synthase (a1,4 glycosidic bonds) and branching enzyme (a1,6 glycosidic bonds)
What else is UDP-glucose used in?
Interconversion of glucose to galactose via epimerase
Give the equation for the completed degradation of glycogen
Glycogen (n residues) + nPi 0.9n Glucose 6-Phosphate + 0.1n Glucose
Why can't you completely degrade glycogen?
A small amount of primer is always preserved
Give first step of glycogen breakdown and enzyme used
1.Glycogen (n residues) + Pi --> Glucose 1-Phosphate + Glycogen (n-1 residues)
glycogen phosphorylase and debranching enzyme
What does glycogen phosphorylase do?
Attacks the a1,4 bonds on glycogen and releases glucose residues as G1P
What does debranching enzyme do?
Attacks glycogen at a1,6 branch points, releasing free glucose
Give second and third steps of glycogen degradation
2.Glucose 1-Phosphate --> Glucose 6-Phosphate (catalysed by phosphoglucomutase)
3.Glucose 6-phosphate + H2O --> Glucose + Pi (catalysed by glucose 6-phosphatase)
Why isn't Glucose 6-phosphatase enzyme present in muscle cells?
Because G 6-P enters glycolysis in muscle cells directly, so it is not required to remove its phosphate. G 6-P converted to glucose in liver cells for distribution round body.
Name all the enzymes used in the degradation of glycogen
How is glycogen metabolism regulated?
Glycogen synthase and glycogen phosphorylase allostericly controlled by high and low energy signals.
Glycogen synthase and glycogen phosphorylase also undergo covalent modification in response to changes in hormones. Glycogen synthase inhibited by phosphorylation and activated by de-phosphorylation, and vice versa for glycogen phosphorylase.
Compare the functions of liver and muscle glycogen
Liver Glycogen – Glucose store for all tissues of the body
Muscle Glycogen – Glucose 6-phosphate store, only used by muscle cells
What do glycogen storage diseases stem from?
An abnormality in one or other key enzymes
3.Glucose 6-phosphatase (liver)
What can glycogen storage diseases cause?
Increased/Decreased amounts of glycogen
- Tissue damage if excessive storage
- Fasting hypoglycaemia (low blood glucose)
- Poor exercise tolerance
Glycogen structure may be abnormal
Usually liver and/or muscle are affected
Clinical severity depends on what enzyme/tissue is affected.
What does gluconeogenesis allow?
the production of glucose when carbohydrates are absent.
When does gluconeogenesis occur?
After 8-10 hours of fasting
Where is the main site of gluconeogenesis?
Give five possible substrates for gluconeogenesis
Pyruvate, lactate and glycerol can be converted to glucose
Essential and non-essential amino acids whose metabolism involves pyruvate or intermediates if the TCA cycle can be converted to glucose
Why can't acetyl co-A be used for gluconeogenesis?
PDH is irreversible
Explain the steps used in gluconeogenesis
Reversible steps of glycolysis are used in gluconeogenesis and irreversible bypassed.
How are steps 1&3 of glycolysis bypassed in the process of gluconeogenesis? Outline reactions and give the enzymes that are used?
Steps 1 & 3 are by-passed by thermodynamically spontaneous reactions catalysed by phosphatases (glucose 6-phosphatase and fructose 1,6-bisphophatase):
Glucose 6-phosphate + H2O --> Glucose + Pi G = -ve
Fructose 1,6-phosphate + H2O --> Fructose 6-phosphate + Pi G = -ve
How is step 10 of glycolysis bypassed in the process of gluconeogenesis? Give reactions and enzymes used.
Step 10 is by-passed by two reactions driven by ATP and GTP hydrolysis and catalysed by pyruvate carboxylase and phosphoenolpyruvate caroxykinase (PEPCK) respectively:
Pyruvate + CO2 + ATP + H2O --> Oxaloacetate + ADP + Pi + 2 H+ G = -ve
Oxaloacetate + GTP + 2 H+ --> Phosphoenolpyruvate + GDP + CO2 G = -ve
What does reaction ten provide a link between? What does it enable?
The TCA cycle and gluconeogenesis. Enables the products of amino acid catabolism that are intermediates of the TCA cycle to be used to synthesise glucose.
What two enzymes are regulated in the process of gluconeogenesis?
PEPCK and Fructose 1,6-bisphosphonate.
How is PEPCK Kinase regulated in gluconeogenesis?
is increased by – Glucagon, Cortisol
is decreased by – Insulin
How is fructose 1,6 bisphosphonate activity regulated in process of gluconeogenesis?
is increased by – Glucagon
is decreased by – Insulin
How does gluconeogenesis contribute to hyperglycaemia in gluconeogenesis?
Low insulin/anti insulin ratio. Key enzymes in gluconeogenesis (PEPCK and Fructose 1,6-bisphosphonate) not inhibited, so continues unchecked.
Why are tags efficient energy stores?
Hydrophobic and stored in an anhydrous form. Highly reduced, so lots of energy.
Why are fats stored?
For prolonged aerobic exercise, stress situations (e.g. starvation, pregnancy)
How is storage of fats controlled? What promotes storage, and what 5 things deplete it?
Storage promotion by insulin
Storage depletion activated by glucagon, adrenaline, cortisol, growth hormone and thyroxine.
How is glycerol transported to adipose tissue?
What three things are required for the synthesis of fatty acids?
acetyl~CoA (from carbohydrates/amino acids), ATP and NADPH
Where is NADPH produced?
In the cytoplasm via the pentose phosphate pathway
What carries out the steps of fatty acid synthesis
a multi-enzyme complex known as the fatty acid synthase complex.
How are C2 units added to the fatty acid chain?
Via malonyl - CoA
How is malonyl A formed What is specific about the enzyme involved?
Via the addition of CO2, with help of enzyme acetyl - coA carboxylase (IS NOT part of fatty acid synthase complex). CO2 IS SUBSEQUENTLY LOST.
How is acetyl-CoA carboxylase important, and what regulates it?
Controls rate of fatty acid synthesis
Allosteric regulation (citrate activates and AMP inhibits)
Regulation by covalent modification of protein structure
Insulin activates by promoting dephosphorylation (removing bulky PO4)
Glucagon & Adrenaline inhibit the enzyme by promoting phosphorylation
Describe how fatty acid oxidation differs from fatty acid synthesis (11)
Fatty acid oxidation --> Fatty acid synthesis
Cycle of reactions that remove C2 --> Cycle of reactions that add C2
C2 atoms removed as acetyle CoA --> C2 atoms added a malonyl CoA
Produces acetyle CoA --> Consumes acetyle CoA
Occurs in mitochondria --> Occurs in cytoplasm
Enzymes separate in mitochondrial matrix --> Multi-enzyme complex in cytoplasm
Oxidative, produces NADH and FAD2H --> Reductive requires NADPH
Requires small amount of ATP to activate the fatty acid --> Requires large amount of ATP to drive the process
Intermediate are linked to CoA --> Intermediates are linked to fatty acid synthase by carrier protein
Regulated indirectly by availability of fatty acids in mitochondria --> Regulated directly by activity of acetyl - CoA carboxylase
Glucagon and adrenaline stimulate --> Glucagon and adrenaline inhibit
Insulin inhibits ---> Insulin Stimulats
Jesus, that took the piss to type.
Give two basic steps of amino acid catabolism
Conversion of C skeleton to useful intermediate
What is an early step of amino acid catabolism? What is produced?
when the (-NH2) amino group is removed – transamination/deamination. This is converted to urea (CO(NH2)2) and excreted in the urine.
What are aminoacids which produce acetyle CoA described as? Why?
Ketogenic, as acetyl CoA can be used to produce ketone bodies
What are amino acids that produce other products to acetyl coA known as, and why?
glucogenic as they can be used for glucose synthesis by gluconeogenesis.
What is the fricking point of transamination?
Creates glutamate, which can then be deaminated. Duh. Not like it took me two hours to work that out. Sarah/Carys, if you're reading this, the whole transamination thing nearly drove me crazy. Also, if you've reached this point in the flashcards, you're doing really well! :D
What enzymes are involved in transamination? What are they specific to?
Aminotransferases. Specific for individual amino acids/similarly structure groups
What is the most commonly used keto acid?
What happens when oxaloacetate is used as a keto acid?
It is converted to aspartate, an important intermediate in urea synthesis
What does cortisol do in transamination?
Trasnaminase synthesis in the liver
Give an example reaction of transamination
Amino acid2 + keto acid1 --> Amino acid1 + ketoacid2
What are L& D amino acid oxidases?
Low specificity enzymes that convert amino acids to keto acids and NH3.
Why do human liver cells have a high activity of D-amino acid oxidase?
Because D-amino acids must not be used for protein synthesis, as the proteins would be structrually abnormal and non-functional. The enzyme converts them to keto acids, which are not optically active
What is glutaminase?
A high specificity enzyme that converts glutamine to glutamate + NH3
What is deamination?
? Removal of an NH3 group from a molecule
Outline the reaction catalysed by glutamate dehydrogenase
Glutamate + NAD+ + H2O a-ketoglutarate + NH4+ + NADH + H+
What is PKU?
Phenylketonuria (PKU) is an inherited disorder in which the urine contains large amounts of phenylketones produced from phenylalanine.
What is the first step in the metabolism of phenyalanine, and defect is present?
The first step in the metabolism of phenylalanine is its oxidation to tyrosine by the enzyme phenylalanine hydroxylase. This enzyme is defective in most PKU cases.
What is the result of the defective phenylalanine hydroxylase enzyme in PKU?
Phenylalanine accumulates in tissues and blood. It is metabolised by other pathways to produce various products including phenylpyruvate that is excreted in the urine. Left untreated can inhibit brain development due to inhibition of pyruvate uptake by phenylpyruvate.
How is PKU diagnosed? How is it subsequently treated?
by the detection of phenylketones in the urine or high phenylalanine blood concn (normal is <0.1mM). The condition is treated with a diet low in phenylalanine.
What is homocystinuria?
a rare inherited autosomal recessive defect in methionine metabolism, in which Type 1 is caused by a deficiency in the cystathionine B-synthase (CBS) enzyme. Causes build up of homocysteine in blood and conversion of homocystein to methionine
What is the normal role of cystathionine B synthase enzyme?
Normally converts homocysteine to cystathionine, which is further converted to cysteine.
What negative effects occur in homocysteinuria, and why?
Chronic elevated plasma levels of homocysteine cause disorders of connective tissue, muscle, CNS and the cardiovascular system.
What are the symptoms of homocysteinuria similar to? What is the common biochemical link?
MARFANS SYNDROME (also known as lukeitis). In homocystinuria, the structure of fibrillin-1 in connective tissue is disrupted - a protein missing in Marfan's syndrome.
What is the clinical relevance of measuring creatinine?
Provides a measure of muscle mass. The amount of excretion of 24hrs is proportional to the muscle mass of the individual unless muscle is wasting (atrophy), or in a high protein diet.
Why are levels of ammonia so low in the blood?
It is very toxic and is thus removed quickly
What are the symptoms of hyperammonaemia?
blurred vision, tremors, slurred speech, coma and eventually death.
What casues toxic effect of ammonia?
its reaction with a-ketoglutarate to form glutamate in mitochondria via glutamate dehydrogenase removing -ketoglutarate from the TCA cycle, which slows, disrupting the energy supply to brain cells
Also affects pH inside cells of the CNS and interferes with neurotransmitter synthesis/release.
How is ammonia detoxified?
by synthesis of N-compounds such as glutamine
by conversion to urea.
Outline glutamine synthesis reaction.
NH4+ + Glutamate --> Glutamine
Glutamine synthetase + ATP
What happens to glutamine in the liver?
It is hydrolysed by glutaminase, releasing ammonia to be disposed of in kidnes.
Why is urea a good method of disposing of unwanted nitrogen?
non-toxic, metabolically inert and has a high nitrogen-content
How is urea synthesis regulated?
Induced by high protein diet and repressed by low-protein/starvation
What two things do inherited diseases of the urea cycle cause?
1.Hyperammonaemia (high blood NH4+ concentration)
2.Accumulation and/or excretion of a particular urea cycle intermediate(s)
How do you treat diseases of urea cycle?
low protein diet and replacing the essential amino acids with keto acids that use up NH4+ when converted to amino acids, therefore lowering NH4+ concentration.
Why might hyperannonaemia arise as a seconday consequence of liver disease?
Because the liver’s ability to remove NH3 from the portal blood is impaired.