Bke2 Biochemistry Exercises
Suggested answers to Group Excercise: Metabolism 2
The pentose-phosphate shunt
- What are the two most important products obtained from the pentose-phosphate shunt?
Answer:
Ribose 5-phosphate for incorporation into nucleotides and nucleic acids, and NADPH for the synthesis of for example fatty acids.
- In what way is the pentose-phosphate shunt coupled to glycolysis?
Answer:
Via transketolase and transaldolase in order to increase the NADPH-pool (Horton p. 417-423).
- What determines the speed of the pentose-phosphate shunt?
Answer:
The reaction glucose 6-phosphate to 6-phosphoglucono-d-lactone, is catalysed by the enzyme glucose 6-phosphate dehydrogenase. This is also the rate limiting step and serves as a control site, since glucose 6-phosphate dehydrogenase is allosterically inhibited by NADH.
- In which tissues are the pentose-phosphate shunt activities greatest?
Answer:
In adipose tissue ('fettvävnad'), mammary glands ('mjölk-körtlar') and in the liver.
Gluconeogenesis
- Explain the difference between glycolysis and gluconeogenesis.
Answer:
In glycolysis the following steps are irreversible:
a) Glucose to Glucose 6-phosphate
b) Fructose 6-phosphate to Fructose 1,6-bis-phosphate
c) Phosphoenolpyruvate to Pyruvate
In gluconeogenesis these three irreversible steps are bypassed by the following reactions:
a) Glucose 6-phosphate + H2O ----> glucose + Pi (catalysed by the enzyme glucose 6-phosphatase)
b) Fructose 1,6-bisphosfate + H2O ----> fructose 6-phosphate + Pi (catalysed by the enzyme fructose 1,6-bisphosphatase)
c) Pyruvate + CO2 + ATP + H2O ----> oxaloacetate + ADP + Pi + 2H+ (catalysed by the enzyme pyruvate carboxylase)
Oxaloacetate + GTP <==> phosphoenolpyruvate + GDP + CO2 (catalysed by the enzyme phosphoenol carboxykinase)
- Biotin (one of the B vitamins) plays a decisive role in gluconeogenesis - please elaborate.
Answer:
Pyruvate carboxylase contains a covalently attached prosthetic group, biotin, which serves as a carrier of activated CO2. If biotin is missing CO2 can not be transferred to pyruvate to form oxaloacetate.
- In contrast to glycolysis, there are certain enzymatic steps in gluconeogenesis that occur in mitochondria. Which steps?
Answer:
The transformation of pyruvate to oxaloacetate and further to malate takes place in mitochondria.
- What is the 'cost' in terms of ATP when synthesizing glucose from pyruvate?
Answer:
6 ATP equivalents (4 ATP and 2 GTP). Four ATP equivalents are needed to overcome the thermodynamic barrier to the formation of the energy-rich compound phosphoenolpyruvate from two molecules of pyruvate. Two ATP molecules are also required to carry out the reverse of the glycolytic reaction catalysed by phosphoglycerate kinase. (Horton p. 408-409).
- Gluconeogenesis and glycolysis are reciprocally regulated. Explain what this means and list the regulating molecules.
Answer:
The same set of molecules regulate the breakdown and the synthesis by inhibition and activation of the different reactions. For example, AMP and Fructose 2,6-bisphosphate stimulate glycolysis and inhibit gluconeogenesis, by acting as activators of the enzyme phosphofructokinase 1, and as inhibitors of the enzyme fructose 1,6-bisphosphatase.
- During strong muscular exertion some muscles work anaerobically, which results in the formation of lactic acid. How can lactate form glucose?
Answer:
Lactate is transported to the liver where lactate is transformed to glucose via gluconegenesis, and glucose is then transported back to the muscle (the Cori cycle).
Glycogen metabolism
- What is the structural difference between glycogen and glucose?
Answer:
Glycogen is a polymer of glucose residues.
- Why can't the glycogen present in skeletal muscles be used by other tissues in the body, in contrast to the case with the liver?
Answer:
In contrast to liver cells, skeletal muscle cells have no possibility to de-phosphorylate the glucose-6-phosphate molecule since the enzyme glucose 6-phosphatase is missing in the skeletal muscle cells.
- How are synthesis and degradation of glycogen regulated?
Answer:
Degradation and synthesis of glycogen is regulated through hormonal control. The hormones trigger a cascade mechanism (see Horton p. 406-407, figures 13.7 and 13.8)
Fatty acid metabolism
- What is meant by saturated and unsaturated fatty acids?
Answer:
Saturated fatty acids contain no double bonds. Unsaturated fatty acids contain one or more double bonds.
- In everyday speech, fat usually means the same as triacylglycerol. What does a molecule of this kind consist of?
Answer:
Triacylglycerol consists of three fatty acids and one molecule of glycerol. The fatty acids are bound by ester bonds to the three hydroxyl groups of glycerol.
- How can glycerol residues from fat be utilised as energy?
Answer:
Glycerol is phosphorylated to glycerol 3-phosphate by the enzyme glycerol kinase. Glycerol 3-phosphate is converted to dihydroxyacetone phosphate, catalysed by the enzyme glycerol phophate dehydrogenase. Dihydroxyacetone phosphate (an intermediate in glycolysis) is isomerised to 3-glyceraldehyde 3-phosphate which can be converted to pyruvate in the glycolytic pathway.
- How are fatty acids broken down for use as energy?
Answer:
Fatty acids are broken down into 2-carbon units, acetyl-CoA, by the b-oxidation pathway.
- Describe how fatty acids are transported into the mitochondrion for further oxidation.
Answer:
Fatty acids are activated on the outer mitochondrial membrane, where CoA is attached to the fatty acid. The acyl group is transfered from the sulphur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine. Acyl carnitine is then shuttled across the inner membrane by a translocase. Carnitine is returned back to the cytosolic side by the translocase in exchange for an incoming acyl carnitine.
Amino acids and urea metabolism
- How is a surplus of amino acids used by the body? Where does this take place in the body?
Answer:
A surplus of amino acids is used as fuel for producing energy, especially in the liver.
- Which enzymatic steps are included when the a-amino group in an amino acid is cleaved off?
Answer:
Transamination and/or oxidative deamination.
- Explain the function of pyridoxal phosphate in amino acid metabolism.
Answer:
Pyridoxal phophate is a coenzyme in all aminotransferases (Horton p. 212-215).
- How do terrestrial vertebrates handle a surplus of ammonium? Which organs metabolise ammonium?
Answer:
Ammonium is transported (as alanine or glutamine) to the liver and metabolised to urea by the urea cycle.
- In which way is the urea cycle linked to the citric acid cycle?
Answer:
The synthesis of fumarate in the urea cycle links the urea cycle with the citric acid cycle.
- What is meant by a glycogen and a ketogen amino acid?
Answer:
Ketogenic amino acids are degraded to acetyl-CoA or acetoacetyl-CoA. Pure ketogenic amino acids can not be used for synthesis of glucose. Glucogenic amino acids are degraded to intermediates which can be used for glucose synthesis in gluconeogenesis.
Exercise answers by Torbjörn Lundh
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