Session 2: Energy Production from Carbohydrates (2)

Question 1

What are some regulatory mechanisms of glycolysis?

Answer 1

Substrate availability, product inhibition, feedback inhibition (allosteric), allostery, covalent modification of enzymes.

Question 2

What is the name of the lactic acid cycle?

Answer 2

Cori cycle

Question 3

Summarise what happens in the lactic acid cycle (Cori cycle).

Answer 3

Lactate released into the blood is taken up by the liver, oxidised to pyruvate, and converted to glucose via gluconeogenesis.

Question 4

How do you define the Cori cycle?

Answer 4

The cycling of lactate and glucose between peripheral tissues (muscle) and liver.

Question 5

In what scenarios is lactate utilisation impaired?

Answer 5

Liver disease, vitamin deficiencies (e.g. thiamine), high alcohol intake, enzyme deficiencies.

Question 6

How much lactate is produced without exercise every day (g)?

Answer 6

40-50g/day

Question 7

How much lactate is produced WITH exercise every day (g)?

Answer 7

30g/5 minutes

Question 8

What are some examples of fructose metabolism disorders and what are the causes?

Answer 8

Essential fructosuria = caused by fructokinase deficiency; fructose intolerance = caused by aldolase deficiency.

Question 9

What are the products of sucrose metabolism?

Answer 9

Fructose + glucose

Question 10

What are the products of lactose metabolism?

Answer 10

Galactose + glucose

Question 11

What are some causes of Galactosaemia (deficiency of galactose)?

Answer 11

Galactokinase deficiency = non-classic galactosaemia; GALT deficiency = classic galactosaemia.

Question 12

What are symptoms of galactosaemia?

Answer 12

Poor feeding, vomiting, diarrhoea.

Question 13

What is the clinical presentation of Glucose-Phosphate Dehydrogenase Deficiency (G6PDH deficiency)?

Answer 13

Haemolytic anaemia, fatigue, pale colour of skin, shortness of breath, jaundice.

Question 14

What are the names given to the insoluble aggregates that attach to RBC membranes in G6PDH deficiency?

Answer 14

Heinz bodies

Question 15

What is the consequence of attachment of Heinz bodies to RBC membranes?

Answer 15

This leads to destruction of RBCs and causes haemolysis by the spleen.

Question 16

What are some common triggers of G6PDH deficiency?

Answer 16

Certain chemicals in medications (e.g. antimalarials such as primaquine), antibiotics, certain foods (fava beans), and infections.

Question 17

Why is there a need for regeneration of NAD+ that isn’t reliant on oxidative phosphorylation?

Answer 17

RBCs have no mitochondria; kidney medulla, lens & cornea have fewer mitochondria; absence of oxygen during vigorous exercise or poorly oxygenated tissues.

Question 18

The rate of lactate production = the rate of lactate __________.

Answer 18

utilisation

Question 19

What are plasma lactate concentrations determined by?

Answer 19

Production of lactate, utilisation of lactate, disposal of lactate (by kidneys).

Question 20

What is considered high lactate (lactic acidosis) in the blood?

Answer 20

> 5mM

Question 21

What are the major enzymes involved in fructose metabolism?

Answer 21

Fructokinase, aldolase.

Question 22

Where is fructose metabolised?

Answer 22

In the liver.

Question 23

What is the process of fructose metabolism?

Answer 23

Fructose is phosphorylated to fructose-1-P by fructokinase enzyme.
Fructose-1-P is cleaved by aldolase enzyme into 2 constituents…
1) Glyceraldehyde = this is converted to glyceraldehyde-3-phosphate
2) DHAP = this is converted to glyceraldehyde-3-phosphate
Glyceraldehyde-3-phosphate then enters glycolysis

Question 24

Cause/pathogenesis of fructose intolerance?

Answer 24

Aldolase deficiency leads to fructose 1,6-bisphosphate accumulation in the liver, causing liver damage and hypoglycaemia.

Question 25

What are the symptoms of fructose intolerance?

Answer 25

Poor feeding in babies, nausea, vomiting, abdominal pain.

Question 26

What is the standard treatment for fructose metabolism disorders?

Answer 26

Elimination of sucrose and fructose from diet.

Question 27

Where is galactose metabolised?

Answer 27

In the liver.

Question 28

What are the main enzymes involved in galactose metabolism?

Answer 28

Galactokinase, galactose-1-phosphate uridyl transferase (GALT).

Question 29

What is the process of galactose metabolism?

Answer 29

Galactose is phosphorylated by Galactokinase into galactose-1-phosphate, which is converted to glucose-1-phosphate by GALT. Then, converted to glucose-6-phosphate

Question 30

What is non-classic galactosaemia?

Answer 30

Galactokinase deficiency leading to accumulation of galactose and galactitol.

Question 31

What is classic galactosaemia?

Answer 31

GALT deficiency leading to accumulation of galactose-1-phosphate and galactitol.

Question 32

What are the pathological consequences of galactose metabolism disorders?

Answer 32

Cataracts due to galactitol accumulation; brain and liver damage.

Question 33

What is the standard treatment for galactose metabolism disorders?

Answer 33

Dietary restrictions of lactose and galactose.

Question 34

What are the two phases of the pentose phosphate pathway?

Answer 34

**Oxidative phase:** Glucose-6-phosphate oxidised to ribulose-5-phosphate. This is catalysed by glucose-6-dehydrogenase enzyme **Non-oxidative phase:** Rearrangement of glycolic intermediates Ribulose-5-phosphate converted to either F-6-P (Fructose-6-phosphate) or G-3-P (Glyceraldehyde-3-phosphate)

Question 35

What is the major enzyme involved in pentose phosphate pathway catalysis?

Answer 35

Glucose-6-dehydrogenase enzyme.

Question 36

What are the primary functions of the pentose phosphate pathway?

Answer 36

Production of NADPH+ and H+, intermediates for glycolysis, and C5 sugars for nucleotides.

Question 37

What is the importance of the pentose phosphate pathway?

Answer 37

Provides NADPH+ and H+ reducing power, maintains a reduced state in glutathione, protects cells from oxidative damage.

Question 38

What is G6PDH deficiency and its impact?

Answer 38

Glucose-6-phosphate dehydrogenase deficiency is a deficiency of the enzyme that catalyses the pentose phosphate pathway. Impact: - Reduced and low levels of NADPH+ and H+ produced (less reducing power) - RBCs most severely affected as pentose pathway in these cells is the ONLY way of generating ATP (no mitochondria - no oxidative phosphorylation). - Oxidative damage as glutathione is in an oxidised state (GSSG) - Haemoglobin and other proteins become cross-linked by disulphide bonds (bridges) which are formed by oxidised S atoms (S-S)Deficiency of glucose-6-phosphate dehydrogenase; leads to reduced NADPH+ and H+, oxidative damage, and haemolysis.

Question 39

What is the name of the insoluble aggregates formed from the cross-linking by disulphide bonds in RBCs (G6PDH deficiency)?

Answer 39

Heinz bodies.

Question 40

What happens when Heinz bodies attach to the RBC membrane?

Answer 40

Haemolysis by the spleen.

Question 41

What are the symptoms of G6PDH deficiency?

Answer 41

Asymptomatic unless triggered; symptoms include haemolytic anaemia, fatigue, pallor, dyspnea, jaundice.

Question 42

Where does the catabolism of galactose occur?

Answer 42

In the liver.

Question 43

Name the reduced form of galactose that accumulates in tissues in galactosaemia.

Answer 43

Galactitol.

Question 44

Name the metabolic pathway whose altering may lead to oxidative damage and the formation of Heinz bodies in erythrocytes.

Answer 44

Pentose phosphate pathway.

Question 45

What is bilirubin?

Answer 45

An orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile.

Question 46

What does abnormally high levels of bilirubin in the blood lead to?

Answer 46

Hyperbilirubinemia causes jaundice (yellow discolouration of the sclera and skin).

Question 47

Propose an explanation for the presence of Heinz bodies in a patient's erythrocytes.

Answer 47

Heinz bodies are produced from G6PDH deficiency, leading to oxidative damage and cross-linking of proteins.

Question 48

Can anaemia and jaundice be related - how?

Answer 48

Anaemia causes RBC degradation, leading to bilirubin accumulation and jaundice.

Question 49

What is the role of glucose-6-phosphate dehydrogenase enzyme?

Answer 49

Enzyme that catalyses the first step of the pentose phosphate pathway.

Question 50

Why can't people with glucose 6 phosphate dehydrogenase deficiency (G6PDH) take antimalarial drugs such as primaquine?

Answer 50

People with G6PDH deficiency struggle to produce enough NADPH in the Phosphate Pentose Pathway (PPP). NADPH is needed to maintain glutathione protein in a reduced state which protects the RBC from oxidative damage by ROS - that's what help keeps the structure of the RBC intact. Primaquine oxidises glutathione which leads to oxidative damage of the RBC - which leads to the production of Heinz bodies.

Question 51

Is galactose a normal constituent of urine?

Answer 51

No.

Question 52

How could you account for the presence of galactose in a patient's urine?

Answer 52

Blood concentration above renal threshold or kidney damage.

Question 53

What are the metabolic consequences of an absence of galactose-1-phosphate uridyl transferase enzyme?

Answer 53

Accumulation of galactose and galactose-1-phosphate, leading to abnormal metabolism.

Question 54

Why do galactosaemic patients develop cataracts?

Answer 54

Cross-linking of lens proteins leads to opacity (cataract).

Question 55

Are the metabolic consequences of an absence of galactokinase similar to those of an absence of galactose-1-phosphate uridyl transferase?

Answer 55

No, absence of galactokinase leads to less severe consequences.

Question 56

What is the standard treatment of a patient with galactosaemia?

Answer 56

Dietary restriction of galactose/lactose; replace with artificial milk.

Question 57

How much lactate is produced every day WITHOUT exercise?

Answer 57

40-50g/day.

Question 58

In what pathological situations is lactate production common?

Answer 58

Shock, congestive heart disease, arterial disease.

Question 59

Examples of situations in which production of lactate is elevated?

Answer 59

Strenuous exercise, hearty eating, shock, congestive heart disease, arterial disease.

Question 60

Examples of situations in which production of lactate is depleted?

Answer 60

Liver disease, vitamin deficiencies, high alcohol intake.

Question 61

What is hyperlactatemia?

Answer 61

2-5 mM in blood, below renal threshold, no change in blood pH.

Question 62

Which are the three regulatory steps of glycolysis?

Answer 62

Reactions 1, 3 and 10: Hexokinase, Phosphofructokinase, Pyruvate kinase.

Question 63

Define lactic acidosis and why it may occur

Answer 63

Lactic acidosis is the elevation of lactate that affects the buffering capacity of the plasma (i.e., there is a fall in plasma pH due to accumulation of lactic acid). Increased lactate can be due to increased lactate production during e.g., strenuous exercise (up to 10g/min), hearty eating, shock and congestive heart disease. Increased lactate can also be due to decreased utilisation of lactate which occurs during e.g., liver disease, enzyme deficiencies (thiamine deficiency), and increased alcohol intake

Question 64

Case study A male infant aged 4 weeks was admitted to hospital. He was a small, and lethargic baby with hepatomegaly and splenomegaly; jaundice was absent on admission, but had been observed the week prior. One week later urine and blood were positive for galactose. Galactose-1-phosphate uridyltransferase (GPT) were present in the blood at low levels. At 8 weeks ocular examinations revealed faint central opacity and a difference in light refraction in the left eye. What’s the diagnosis?

Answer 64

Galactosaemia

Question 65

Case study 21-year-old male, working as a tour guide was admitted to A&E because of severe jaundice. History revealed he had taken as a prophylactic measure, an antimalarial, Primaquine, to protect himself. The day after intake of Primaquine he noticed yellowish discolouration of his face progressing down to the lower extremities. Past history revealed a previous admission when he was 12 years old for the same complaint, when he was given Sulphonamides for a UTI. Laboratory examinations revealed low haemoglobin, RBC’s showed Heinz Bodies. What’s the diagnosis?

Answer 65

G6PDH deficiency