Session 4 Flashcards
What is Glycogen synthesis called?
Glycogenesis
What enzyme catalyses the first step in Glycogenesis?
Hexokinase
What enzyme catalyses the second step in Glycogenesis?
Phosphoglucomutase
What enzyme catalyses the fourth step in Glycogenesis?
Glycogen synthase & Branching enzyme
What enzyme catalyses the first step in Glycogen breakdown?
Glycogen phosphorylase attacks the alpha 1,4 bonds & Debranching enzyme attacks alpha 1,6
What enzyme catalyses the second step in Glycogen breakdown?
Phosphoglucomutase
What enzyme catalyses the third step in Glycogen breakdown?
Glucose 6-phosphatase
Contrast the Glycogen stores in Muscles and the Liver
Muscle - G6P, muscle only
Liver - Glucose for all tissues of the body
Explain the clinical consequences of Glycogen storage disease
Abnormality in enzymes of Glycogen metabolism; Tissue damage if excessive storage Fasting hypoglycaemia Poor exercise tolerance Glycogen structure may be abnormal
Define Gluconeogenesis
The process where Glucose is produced when there are no Carbohydrates.
Liver is the main site
Reversible steps of glycolysis used in gluconeogenesis, irreversible bypassed.
Name some of the substrates for Gluconeogenesis
Pyruvate Lactate Glucerol AA NOT Acetyl CoA
WHat 3 steps of Glycolysis are bypassed in Gluconeogenesis?
1, 3 & 10
How are steps 1 & 3 of Glycolysis bypassed in Gluconeogenesis?
Thermodynamically spontaneous reactions catalysed by glucose 6-phosphatase and fructose 1,6-bisphophatase
How is step 10 of Glycolgysis bypassed in Gluconeogenesis?
2 reactions catalysed by pyruvate carboxylase and PEPCK (Use ATP)
Which reaction provides a ‘link’ between the Krebs cycle and Gluconeogenesis?
Step 10 reaction enables products of AA catabolism (intermediates of TCA cycle) to synthesise glucose.
How is Gluconeogenesis regulated?
Hormonal control on PEPCK and Fructose 1,6-bisphosphonate
Increased by Glucagon, decreased by Insulin
What controls Triacylglycerol storage?
Promoted by Insulin
Depleted by anti insulin hormones (Glucagon, Adrenaline, Cortisol, Thyroxine, GH)
How are Fatty acids degraded?
Beta oxidation. 2C removed at a time (As Acetyl CoA) until only 2 left.
Needs NAD+, FAD & O2
How are fatty acids synthesised?
Lipogenesis - Synthesised from Acetyl CoA using ATP and NADPH
Fatty acid synthase complex adds 2Cs at a time by adding 3Cs and having CO2 lost
How is Lipogenesis controlled?
Acetyl~CoA carboxylase enzyme (Converts Acetyl CoA to 3C compound)
Allosteric regulation - citrate activates and AMP inhibits
Regulation by covalent modification - Insulin activates by promoting dephosphorylation. Glucagon & Adrenaline inhibit the enzyme by promoting phosphorylation
How are Amino acids catabolised?
Each has its own pathway;
Amino group removed –> Urea (Deamination/Transamination)
Remaining C skeleton reused
What are Ketogenic Amino acids?
Ones that can produce Acetyl CoA as it goes on to make Ketone bodies
What are Glucogenic Amino acids?
Ones that produce molecules which can be used for Glucose synthesis in Gluconeogenesis
What enzymes are used in Transamination?
Aminotransferases
What enzymes are used in Deamination?
L & D-amino acid oxidases (Convert AA to Keto acids)
D amino acids must NOT be used in protein synthesis as proteins would be structurally abnormal & non functional
Define Phenylketonuria (PKU)
Inherited disorder
Urine contains large amounts of phenylketones produced from phenylalanine
Which enzyme is usually defective in PKU?
Phenylalanine hydroxylase. (Oxidises Phenylalanine to Tyrosine)
Results in high levels of Phenylalanine - metabolised by other pathways to produce various products including phenylpyruvate - excreted in the urine.
How is PKU diagnosed?
Detection of phenylketones in the urine or high phenylalanine blood concn (normal is <0.1mM).
How is PKU treated?
A diet low in Phenylalanine
Left untreated can inhibit brain development due to inhibition of pyruvate uptake by phenylpyruvate
Define Homocystinuria
Autosomal recessive defect in methionine metabolism
Type 1 - deficiency in CBS enzyme
How is Homocystinuria detected?
Elevated levels of homocysteine and methionine in plasma (and homocystine – the oxidised form of homocysteine in the urine)
What are the consequences of Homocystinuria?
Chronic elevated plasma levels of homocysteine cause disorders of connective tissue, muscle, CNS and the cardiovascular system - Easily confused with Marfan’s syndrome in children
Why do you measure blood and urine Creatinine?
Breakdown product of Creatine.
Produced at constant rate by spontaneous muscle atrophy
Amount of excretion in 24hrs is proportional to the muscle mass of the individual. - measure of muscle mass.
Why is Ammonia metabolised by the body?
Toxic - rapidly detoxified & removed. Peripheral blood concentration is normally kept very low (25-40microM)
Why is Ammonia toxic?
CNS very sensitive.
Involves reaction with alpha-ketoglutarate to form glutamate in mitochondria via glutamate dehydrogenase removing alpha¬-ketoglutarate from the TCA cycle- disrupting energy to brain cells.
Affects pH in cells of CNS & interferes with neurotransmitter synthesis/release.
What are the signs of Hyperammonaemia?
Blurred vision, tremors, coma & death
Seen in Liver disease
How can Ammonia be detoxified?
Synthesis of N-compounds such as glutamine (Requires ATP and glutamine synthetase) or by conversion to urea
Glutamine is transported to Kidneys - hydrolysed by glutaminase releasing ammonia - disposed of in the urine
Why is Urea beneficial?
Very soluble in water
It is non-toxic, metabolically inert and has a high nitrogen-content (47%)
Good way of disposing of nitrogen
How is Urea synthesis regulated?
NOT feedback inhibition because the function of the cycle is to dispose.
Enzymes are inducible by a high-protein diet, and repressed by low-protein/starvation.
What is important to remember when treating people who have suffered starvation?
Gradual re-introduction of protein to prevent hyperammonaemia as the enzymes can slowly be reactivated
What do diseases of the Urea cycle cause?
Hyperammonaemia
High concentration/excretion of the urea cycle intermediates.
Usually mental retardation
Can cause death
How do you treat diseases of the Urea cycle?
Low protein diet and replacing essential AA with keto acids that use NH4+ when converted to amino acids, so lowers NH4+ concentration
