Session 1: Carbohydrates, glycolysis, pentose phosphate pathway Flashcards
What are the four stages of catabolism?
- Breakdown to building block molecules
- Breakdown to metabolic intermediates
- release of ‘reducing power’
- Breakdown to metabolic intermediates
- Kreb’s cycle
- Oxidative phosphorylation
- conversion of ‘reducing power’ into energy currency, ATP
- Oxidative phosphorylation
What happens in stage 1 of carbohydrate metabolism? (3)
- Salivary amylase - starch/glycogen -> dextrins (oligosaccharides)
2A. Pancreatic amylase - monosaccharides
2B. Small intestine - disaccharidases attached to brush border of epithelial cells (lactase, sucrase, pancreatic amylase, isomaltase)
How can lactose intolerance come about?
- Primary lactase deficiency - lactase allele not expressed in adulthood
- Secondary lactase deficiency - reversible injury to small intestine
- Congenital lactase deficiency - autosomal recessive
How do monosaccharides reach the bloodstream?
Active transport
- SGLT1 (gut to intestinal epithelial cells)
- GLUT2 from intestinal epithelial to blood)
How are monosaccharides taken up by cells from blood?
Facilitated diffusion - GLUT 1-5
Where is GLUT2 found? (4)
- Kidney
- Liver
- Pancreatic beta cells
- Small intestine
Where is GLUT4 found? What is characteristic of this transport protein?
- Adipose tissue
- Striated muscle
It is insulin-regulated
What is the average blood glucose level?
~5 mM
Which cells have an absolute requirement for glucose and why?
- RBCs - no mitochondria
- Neutrophils - use mt for oxidative burst
- Innermost cells of kidney medulla
- Lens of the eye - poor oxygen supply
Describe the CNS’ (brain’s) dependency on glucose.
Prefers glucose but can use ketone bodies for some energy requirements in times.
Concentration should meet or exceed Km for transporter to move glucose across BBB
What is produced in glycolysis?
Each glucose molecule produces:
- 2 pyruvates (3C intermediates)
- 2 NADH
- 2 ATP
- 6C intermediates
Where does glycolysis take place?
Cytosol
What are the 3 main enzymes involved in glycolysis?
- Hexokinase (glucokinase in liver)
- phosphofructokinase-1
- Pyruvate kinase
What is the committing step in glycolysis?
Fructose-6-P to fructose 1,6-bis-P
What is the main regulator of glycolysis?
PFK
What regulates PFK in the muscle?
High ATP - inhibits
High AMP - stimulates
What regulates PFK in the liver?
Insulin - stimulates
Glucagon - inhibits
Name all the regulators of glycolysis
- Insulin and glucagon
- ATP and AMP
- high NADH therefore low NAD+ inhibits
- G6-P product inhibition of hexokinase
- Insulin:glucagon ratio stimulates pyruvate kinase
What is the significance of fructose 1,6-bis phosphate being broken down to DHAP (and G3P)?
DHAP important to triglyceride and phospholipid biosynthesis - forms glycerol phosphate which forms the backbone of triacylglycerol
- produced in adipose and liver
Which enzyme is involved in converting DHAP to glycerol phosphate?
Glycerol 3-phosphate dehydrogenase
Which enzyme converts 1,3-bis phosphoglycerate to 2,3-bis phosphoglycerate?
Bisphosphoglycerate mutase
What is the significance of 2,3-BPG?
Produced in RBCs to regulate affinity of Hb for O2 - BPG reduces affinity
How is NAD+ regenerated in glucose metabolism? (2)
- Stage 4 - oxidative phosphorylation
2. Lactate dehydrogenase converts pyruvate to lactate and NAD+
Which parts of the body have troubles with regeneration of NAD+ and why?
- RBCs - no Kreb’s cycle or oxidative phosphorylation because no mitochondria
- Gut and muscle - oxidative phosphorylation needs O2 and these organs get reduced O2 supply sometimes
What happens to pyruvate in tissues with low O2 supply?
Lactate dehydrogenase reduces it to lactate using NADH, producing NAD+
What happens to lactate once anaerobic respiration occurs in tissues?
Travels in blood to heart, liver and kidney
What happens to lactate in the heart?
- Lactate dehydrogenase oxidises lactate to pyruvate using NAD+, producing NADH
- pyruvate is then oxidised to produce energy and CO2 (Kreb’s cycle)
What happens to lactate in the liver and kidney?
- lactate gets oxidised to pyruvate by lactate dehydrogenase
- pyruvate forms glucose through gluconeogenesis and is released back into blood
How does fructose enter glycolysis?
- Fructose -> Fructose-1P (Fructose kinase)
- Fructose-1P -> Glyceraldehyde + DHAP (Aldolase)
- Glyceraldehyde -> G3P (Triose kinase)
- DHAP -> G3P (TPI)
- G3P x 2 enters glycolysis
Which organ metabolises fructose?
Liver
What is essential fructosuria?
Which enzyme is missing?
Fructose in urine - fructokinase missing
Which enzyme is missing in patients with fructose intolerance? What happens as a result of this?
Aldolase is missing - fructose-1P accumulates in liver and leads to liver damage
Which molecules does the pentose phosphate pathway start from?
Glucose-6P
Which important molecules does the pentose phosphate pathway produce?
NADPH
Ribose-5P (ribose sugars)
What is NADPH required for? (3)
- Reducing power for biosynthesis (fatty acids, steroids)
- Maintenance of glutathione levels
- Detoxification reactions
What do C5 ribose sugars help synthesise?
Nucleotides
DNA and RNA
What is the rate-Iimiting enzyme in the pentose phosphate pathway?
Glucose-6P dehydrogenase
Where in the cell does the pentose phosphate pathway occur?
Cytosol
