Metabolism 5, 6 & 7

Question 1

What is the concept of metabolic problems: carbohydrates (4)

Answer 1

• Diseases involving the Krebs cycle reactions are rarely seen
• Diseases due to altered glycolysis are more common which causes RBCs to be severely affected
• This can be a deficiency of one or more enzymes in glycolysis that can destroy RBCs → haemolytic anaemia
• Pyruvate kinase deficiency is most common (accumulation of 3-phosphoglycerate)

Question 2

What is an example of a metabolic problem involving carbohydrates (3)

Answer 2

1. McArdle’s syndrome: autosomal recessive genetic disorder
   
   1. Defect in glycogen phosphorylase gene – inability to break down glycogen (to glucose) in muscle
   2. the patient should avoid intensive/excessive exercise

Question 3

How are fatty acids metabolised (beta-oxidation) (3)

Answer 3

• Fatty acids are first joined to coenzyme A (CoA), requiring energy (ATP → AMP)
• Fatty acid catabolism is a four-step cycle which is repeated until the long-chain fatty acid is broken down to units of acetyl-CoA
• One cycle of beta-oxidation results in a fatty acid shortened by two carbons and one molecule of acetyl-CoA

Question 4

What problems may occur with excess fatty acids (4)

Answer 4

• If consumed in excess of usage, surplus stored as triglycerides within the adipose tissue
• Some can be deposited within vessels of the CV system, which can cause atherosclerosis and heart disease
• Excess fat also linked to increased risk of cancer (breast and colon)
• If intake of lipids is low, risk of deficiency disease

Question 5

What are the beta-oxidation reactions (4)

Answer 5

1. Oxidation by FAD (FAD → FADH2)
2. Hydration
3. Oxidation NAD- (NAD- → NADH)
4. Cleavage of acetyl CoA

Question 6

How many molecules of acetyl-CoA are produced by catabolism of Palmitic acid, CH3(CH2)14CO2H, and how many cycles of the b-oxidation pathway are needed? (3)

Answer 6

1. Palamic acid has 16 carbons
2. Each round of beta-oxidation removes 2 carbons from the fatty acid chain as one acetyl-CoA molecule
3. The 16 chain carbon chain will go through 7 rounds (as the final cycle splits the remaining 4 carbons into two acetyl-CoA) of beta -oxidation, producing 8 molecules of acetyl-CoA

Question 7

How many molecules of acetyl-CoA are produced by catabolism of Arachidic acid, CH3(CH2)18CO2H, and how many cycles of the beta-oxidation pathway are needed? (2)

Answer 7

1. Arachidic is has 20 carbons
2. Each round of beta-oxidation removes 2 carbons from the fatty acid chain as one acetyl-CoA molecule
3. The 20 chain carbon chain will go through 9 rounds (as the final cycle splits the remaining 4 carbons into two acetyl-CoA) of beta -oxidation, producing 10 molecules of acetyl-CoA

Question 8

How do you work out how many molecules of acetyl-CoA are produced by the catabolism of an acid, and how many cycles of the beta-oxidation pathway are needed (2)

Answer 8

1. Molecules of acetyl-CoA produced = number of carbons / 2
2. Cycles of the beta-oxidation pathway needed = Molecules of acetyl-CoA - 1 or ((number of carbons / 2) - 1)

Question 9

What conditions are there for the Krebs cycle to take place (2)

Answer 9

• Acetyl-CoA enters Krebs cycle if there is a balance between fats and carbohydrates
• Must be sufficient oxaloacetate from carbohydrate catabolism to combine with the acetyl-CoA

Question 10

How does fasting conditions or diseases such as diabetes affect the krebs cycle (4)

Answer 10

• Oxaloacetate used to produce glucose via gluconeogenesis
• Acetyl-CoA cannot enter Krebs cycle as there is no oxaloacetate to combine with
• Instead forms acetoacetate and 3-hydroxybutyrate – collectively known as ketone bodies
• Acetoacetate is slowly decarboxylated to acetone which can be detected in the breath and urine

Question 11

What is diabetes and what are the different types of diabetes? (3)

Answer 11

Diabetes occurs when the body doesnt produce enough insulin or the body’s cells dont respond to insulin properly causing high levels of blood sugar, or blood glucose.

Type 1 - autoimmune - pancreatic cells are attacked by the immune system, so the pancreas produces little or no insulin

Type 2 - the body becomes resistant to insulin or doesnt make enough insulin

Question 12

Why do ketone bodies form in diabetic patients? (4)

Answer 12

1. Insulin dediciency or ineffectiveness - prevents glucose from entering cells, leading to alternative fuel use
2. Shift to fat as an alternate energy source
3. Ketogenesis in the liver - produces ketone bodies as a byproduct of fat metabolism
4. Accumulation of ketones in the blood (ketosis) - without adequate insulin regulation high ketone levels results in ketosis and potentially ketoacidosis

Question 13

What are the symptoms of ketoacidosis? (8)

Answer 13

1. feeling thirsty
2. needing to pee more often
3. stomach pain, feeling sick or being sick
4. diarrhoea
5. breathing more deeply than usual
6. breath that smells fruity (like pear drop sweets or nail polish remover)
7. feeling tired, sleepy or confused
8. blurred vision

Question 14

Where does metabolism of proteins take place and what is produced (3)

Answer 14

• Amino acid catabolism usually takes place in the liver; some can occur in the muscle
• Amino acids from proteins can be converted into glucose
• Excess amino acids are converted to triacylglycerols and stored in the adipose tissue

Question 15

What are the steps of amino acid metabolism (4)

Answer 15

1. Amino group is removed using transaminase enzymes and transferred to an acceptor (e.g. alpha-ketoglutarate) to form glutamate
2. The acceptor is then oxidatively deaminated to form the ammonium cation (NH4+)
3. NH4+ is converted to urea for excretion
4. The remaining carbon skeleton metabolised by the formation of glucose, a Krebs cycle intermediate, or acetyl-CoA

Question 16

What are the fates of amino acid catabolism (4)

Answer 16

• The 20 common amino acids are degraded by different pathways to produce seven products
• The seven products are metabolic intermediates of either glycolysis or the Krebs cycle.

All amino acids are broken down to either:

• Fumarate, alpha-ketoglutarate, oxaloacetate, pyruvate or succinyl-CoA (glucogenic amino acids)
• Acetyl-CoA, acetoacetyl-CoA (ketogenic amino acids)

Question 17

What are the amino acid metabolic problems (7)

Answer 17

• Genetic disorders
• Alkaptonuria: defect in enzyme involved in tyrosine metabolism
  
  • Toxic by-product accumulates in the blood and is excreted in the urine which turns dark upon air oxidation
  • Also causes cartilage damage (→ osteoarthritis), coronary heart disease, and kidney stones
• Phenylketonuria: deficiency of enzyme which converts phenylalanine to tyrosine
  
  • Phenylalanine accumulates and converted to phenylpyruvate which is detected in the urine
  • Severe mental problems occur if defect not diagnosed soon after birth

Question 18

What is the electron transport chain (8)

Answer 18

• The part of aerobic respiration that uses free oxygen as the final electron acceptor of the electrons removed from intermediate compounds in glycolysis
• Composed of four large, multi-protein complexes embedded in the inner mitochondrial membrane and two small diffusible electron carriers shuttling electrons between them.
• Electrons are passed through a series of redox reactions, with a small amount of free energy to transport hydrogen ions across a membrane.
• This process contributes to the gradient used in chemiosmosis
• The electrons passing through the electron transport chain gradually lose energy
• High-energy electrons donated to the chain by either NADH or FADH2 complete the chain
• Low-energy electrons reduce oxygen molecules and form water.
• The end products of the electron transport chain are water and ATP.

Question 19

What is oxidative phosphorylation (2)

Answer 19

• The production of ATP using the process of chemiosmosis in mitochondria
• The addition of a phosphate to ADP, forming ATP, using the potential energy of the hydrogen ion gradient.