MCBG Session 6 - Catabolic Pathways (Part 1)

Question 1

What is catabolism?

Answer 1

The conversion of biological molecules into smaller ones (intermediary metabolites)

Question 2

Give a brief overview of the 4 major stages of catabolism (of glucose)

Answer 2

1) Breakdown of macromolecules (carbs, proteins, fats, alcohol) into building block molecules.
2) Degradation of building block molecules into smaller precursors (e.g.: pyruvate) - AKA: Glycolysis
3) TCA cycle (Krebs) - oxidation of acetyl CoA into CO2 and production of NADH/FADH2
4) Electron transport & oxidative phosphorylation to produce large amounts of ATP.

Question 3

• What is the general formula of carbohydrates?
• What 4 different kinds of carbohydrate can you get (give an example of each)
• What are the 3 kinds of monosaccharide sugars?

Answer 3

• (CH2O)n
• Monosaccharide (glucose), Disaccharide (lactose), Oligosaccharide (dextrin), Polysaccharide (starch)
• Triose, Pentose & Hexose sugars

Question 4

What are the constituents of lactose, sucrose + maltose

What is the normal blood glucose concentration?

Answer 4

Lactose = Glucose + Galactose
Sucrose = Glucose + Fructose
Maltose = Glucose + Glucose
- 5mM

Question 5

How are carbohydrates initially digested?

Answer 5

• In the mouth, salivary amylase break polysaccharides into dextrins.
• Pancreatic amylase breaks down polysaccharides into monosaccharides
• Small intestine - disaccharides attached to brush border of epithelial cells broken down by respective enzymes, e.g.: lactase for lactose (breaking a-1,4 glycosidic linkages)

Question 6

Why is cellulose not digested in the human GIT?

Answer 6

• Humans do not contain enzymes required to break down B1,4-glycosidic linkages present in cellulose.

Question 7

• What is the biochemical basis of lactose intolerance?

- What leads to the symptoms?

Answer 7

• Lack of lactase enzyme - can be primary (absence of lactase persistance allele), secondary (damage to SI epithelium) or congenital (autosomal recessive defect in lactase gene).
• Lactose not broken down, remains in GIT as osmolyte, draws water into GIT, leads to bloating, flatulence, Diarrhoea, Vomiting etc.

Question 8

• Which 4 tissues need glucose as an absolute requirement?

- How much glucose does the brain use per day?

Answer 8

• RBC’s, Neutrophils, Innermost cells of the kidney medulla & Lens of the eye (approx 40g glucose/day)
• 140g per day

Question 9

How is glucose absorbed into the blood stream from the GIT?

Answer 9

1) Glucose taken up from apical side into intestinal epithelial cell via active transport from SGLT1.
2) Glucose moves into capillary/blood stream via passive diffusion through glucose (GLUT) transporters
3) Can be GLUT1-5 - GLUT2 in GIT

Question 10

What are the 4 main functions of glycolysis?

Answer 10

1) Oxidation of glucose to 2 x 3C pyruvate molecules
2) Production of NADH (2 per glucose)
3) Synthesis of ATP from ADP (4 produced, 2 used therefore net of 2xATP per glucose)
4) Produces 6C and 3C intermediates

Question 11

• Where does glycolysis occur?
• What type of reactions occur in glycolysis?
• Is there any loss of CO2?
• Is it a reversible or irreversible pathway?

Answer 11

• Glycolysis is cytosolic
• Oxidative (exothermic) reactions
• 6C molecules –> 2 x 3C molecules (so no loss of CO2)
• Irreversible

Question 12

What are the 3 irreversible steps in glycolysis + the enzymes that catalyse them? (and the steps therefore subject to regulation)

Answer 12

1) Step 1 - phosphokinase (PK)
2) Step 3 - phosphofructokinase-1 (PFK1) - key control enzyme
3) Step 10 - Pyruvate kinase

Question 13

What 2 important intermediate metabolites can be produced during glycolysis
What is the committing step in glycolysis?

Answer 13

1) Glycerol Phosphate (from DHAP via glycerol-3-phosphate dehydrogenase) - important in triglyceride and phospholipid synthesis,
2) 2,3-BPG (from 1,3-BPG via bisphosphoglycerate mutase) - regulates Hb O2 affinity (makes it favour oxygen release)
- Step 3 - The step that commits glucose to metabolism via glycolysis.

Question 14

What is the role of Lactate Dehydrogenase (LDH) in glucose metabolism?

Answer 14

• In low O2 conditions, NADH must be re-oxidised to NAD+ for ATP synthesis in glycolysis to occur (Step 6 in particular)
• LDH catalyses the reaction of NADH, protons + pyruvate to reform NAD+.
• However this also produces lactate, which is converted back into pyruvate in the liver - also by LDH.

Question 15

• What is the normal blood conc of lactate?

- What is the blood conc for hyperlactaemia + lactic acidosis

Answer 15

• <1mM lactate
• 2-5 mM
• > 5mM - critical marker of acutely unwell patient

Question 16

How is fructose metabolised in the body?

Answer 16

1) Fructose to Fructose-1P via fructokinase
2) Fructose 1P to glyceraldehyde via aldolase
3) Glyceraldehyde to glyceraldehyde-3P via triose kinase

G3P is then used in glycolyis.

Question 17

How is galactose metabolised in the body?

Answer 17

1) Galactose to Galactose-1P via galactokinase
2) Galactose-1P to Glucose-6P via uridyl transferase
3) OR Galactose-1P to UDP-glucose via UDP-galactose epimerase

Question 18

What is galactosaemia + what is it caused by?

Answer 18

• Inability to breakdown galactose, due to a deficiency in one of the three enzymes involved.
• Uridyl transferase deficiency most common so get accumulation of galactose and G-1-P.

Question 19

How does galactosaemia lead to cateracts?

Answer 19

• Build up of galactose converted to galactitol via aldose reductase
• This converts NADPH to NADP+, depletes NADPH which maintains free sulphydryl (SH) groups on proteins
• Leads to inappropriate disulphide bond formation, loss of structural integrity of certain proteins
• E.g.: lens of the eye, leading to cateracts

Question 20

What is the clinical treatment for galactosaemia?

Answer 20

• Remove lactose from diet (as it is a disaccharide of glucose + galactose).