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
What happens during phase 2?
Complex reactions convert any unused C5 sugar phosphates into intermediates of glycolysis
- 2 fructose-6-phosphates
- 1 Glyceraldehyde-3-phosphate
No ATP produced
Loss of CO2 therefore irreversible
Controlled by NADP+/NADPH ratio at G6P dehydrogenase
What is NADPH used for?
Biosynthetic reducing power
- e.g. lipid synthesis (high activity in liver and adipose tissue)
Maintain free -SH (cysteine) groups on certain proteins
- Prevent oxidation to S-S bonds (disulphide bonds)
Detoxification process
What are C5 sugars required for?
Needed for nucleic acid synthesis for DNA and RNA
High activity in dividing tissues
What is the rate limiting enzyme in the pentose phosphate pathways?
Glucose-6 phosphate dehydrogenase
What is glucose-6-phosphate dehydrogenase deficiency?
Common inherited disorder
Deficiency in enzyme G6PDH
Important for production of NADPH
Maintain -SH and prevent disulphide bond formation
Deficiency means function and structure of proteins is altered
↓G6PDH in RBC → ↓NADPH→ disulphide bonds formation→ aggregated proteins → Heinz bodies → haemolysis (destruction of RBC)→ lens of eye→ cataracts
