L6: Energy production- Carbohydrates II Flashcards
What are the important intermediate in glycolysis?
Glycerol phosphate
- Triglyceride and phospholipid biosynthesis
- Produced from DHAP in adipose and liver
- Lipid synthesis in liver requires glycolysis
2,3-bisphosphate
- Produced from 1,3-bisphophoglycerate in RBC
- Important regulator of O2 affinity in haemoglobin
- Present in RBCs at the same molar concentration as haemoglobin
Why is lactate dehydrogenase useful?
Allows glycolysis to continue when there is no O2
- RBC or anaerobic respiration
Produced from pyruvate
NADH + H+ + pyruvate → NAD+ + lactate
Then reconverted back to pyruvate in heart, liver and kidney
How do the lactate levels vary?
Without major exercise 40-50g/24hrs → RBC, skin, brain, skeletal msucle, GI tract Strenous exercise 30g/5 min → plasma levels x10 in 2-5 mins → back to normal after 90mins Pathological situations → shock, congestive heart disease
What determine the plasma lactate levels?
- Production
- Utilisation (liver, heart, muscle)
- Disposal (kidney)
What happens if lactate levels rise?
Hyperlactarmia
- 2-5mM
- Below renal threshold
- No change in blood pH due to buffering capacity
Lactic acidosis
- Above 5mM
- Above renal threshold
- Blood pH lowered, more H+ ions in the blood
- Critical marker in acutely unwell patient
What is fructose?
Monosaccharide found in fruit
Sucrose= fructose + glucose
Broken down by fructase
How is fructose metabolised?
In the liver
Catalysed by enzymes frucokinase and aldolase to glyceraldehyde-3-phosphate
Intermediate of glycolysis
What are some clinical complications associated with fructose metabolism?
Essential fructosuria → fructose in urine → No clinical signs → fructokinase enzyme missing Fructose intolerance → Fructose-1-phosphate accumulates in the liver → Aldolase enzyme missing → treatment- remove fructose from diet
What is galactose?
Monosaccharide
Lactose- disaccharide of galactose and glucose
Metabolised by lactase
How is galactose metabolised?
In liver Galactokinase Uridyl transferase UDP-galactose epimerase Galactose → Galactose-1-P → glucose-1P using enzymes galactokinase and uridyl transferase Glucose-1P can enter glycolysis OR Galactose-1-P → UDP-galactose using enzymes UDP-galactose epimerase
What is galactosemia?
Deficiency in transferase enzyme or kinase enzyme
Unable to utilise galactose
Galactokinase deficiency (rare)→ galactose accumulates
Transferase deficiency (common)→ galactose and galactose-1-P accumulates
What is the problem with galactosemia?
Galactose enters other pathways
Galactose → Galactitol
using enzyme aldose reductase and NADPH (coverted to NAD+)
Uses up NADPH stores→ prevents maintenance of free sulphydryl groups on proteins
Innappropriate disulphide bond formation
Eyes→ cataracts
In addition non-enzymatic glycosylation of less proteins due to high galactitol
Galactose-1P affect liver, kidney and brain
Increased galactose + galactitol→ raised intraoccular pressure→ glucoma → blindness
Treatment→ remove galactose from the diet
What is the pentose phosphate pathway for?
- Hexosemonophosphate shunt
- In high energy state (↑[ATP]) glucose-6-phosphate enters a different pathway
- Major function
→ NADPH production
→ production of C5 ribose sugars
No ATP or CO2 produced but it is oxidative
What are the two phases of the pentose phosphate pathway?
Phase 1- Oxidative decarboxylation
Phase 2- Rearrangement of glycolytic intermediates
What happens during phase 1?
6C is converted to 5C sugar with production of 2NADPH and 2H+ and CO2
Glucose-6P + 2NADP+ → C5 sugar phosphate + 2NADPH + 2H+ + CO2
Using enzyme glucose 6-phosphate dehydrogenase