8 - Carbohydrates + Glycolysis Flashcards
What are two important intermediates from glycolysis?
- Glycerol Phosphate (from oxidation of DHAP) - Triglyceride and phospholipid biosynthesis in liver and adipose.
- 2-3 Bisphosphoglycerate (from 1,3 BPG) - Regulator of haemoglobin’s O2 affinity as makes it rigid
Why is lactate dehydrogenase important in RBC?
RBC have no mitochondrial stage of metabolism so have no way of oxidising NADH back to NAD to be used for more ATP synthesis. LDH allows NAD to be produced so glycolysis can continue
What is normal lactate production and how can this vary?
40 - 50g a day from RBC and skeletal muscle
Can increase when:
— Exercising e.g 30g in 5 mins
— Hearty eating
— Shock
— Congestive Heart Disease
— Thyamine deficiency
— Liver disease
Why would thiamine deficiency lead to lactate acidosis?
Thiamine (Vitamin B) is cofactor in converting pyruvate to acetyl coA. If no thiamine, pyruvate converted to lactate instead
How does LDH work?
Reduces pyruvate to lactate using NADH which oxidises NADH back to NAD to be used in glycolysis. Allows glycolysis to keep occurring
Explain how LDH works as a cycle?
- Lactate released into blood by muscle and RBC
- Metabolised by liver and heart
What does plasma lactate concentration depend on?
- Production
- Utilisation (heart, kidney, lungs)
- Disposal (kidney)
What is hyperlactaemia and lactic acidosis?
- Normal 1mM/L
- Hyper is 2-5 mM/L, no change in blood pH as blood buffers it
- Acidosis is above 5mM/L and blood pH is lowered as above renal threshold to buffer. Sign of critically ill patient
How is fructose (and galactose) metabolised?
In liver
What are two issues with fructose metabolism and what are the consequences?
- Essential fructosuria: Fructokinase missing so fructose builds up and excreted. No major issue just not efficient metabolism
- Fructose Intolerance: Aldolase missing. Fructose-1-p build up in liver causes damage. Remove fructose from diet
What is galactosemia?
Genetic disorder that prevents metabolism of galactose.
Due to lack of 1 of 3 enzymes:
- Galactokinase
- Uridyl transferase
- UDP-galactose-epimerase
What paths can the metabolism of galactose take?
Glycolysis or Glycogenesis
How can galactosemia be caused?
- Galactokinase deficiency (rare) - Galactose accumaltes but just excreted
- Transferase deficiency (common) - Galactose and galactose 1-p accumulate. Galactose enters other pathways it shouldn’t (galactitol) and uses NADPH so cataracts. Galactose 1-p damages liver, kidney, brain
- Treatment: No lactose in diet
What are the symptoms of galactosemia and causes of the symptoms?
- Cataracts - Depleted NADPH levels. NADPH usually prevents disulphide bridges forming between proteins, without NADPH aggregates of proteins can form on lens of eye.
- Glaucoma - Build up of galactose and galactitol causes intra-ocular pressure and can lead to blindness
- Liver, Heart, Kidney, Brain damage - Accumulation of galactose-1-p
Explain the diagram of all three monosaccharides entering glycolysis.
What is the pentose phosphate pathway?
1. Oxidative decarboxylation: G-6-P converted to C5 sugar and CO2, producing NADPH for biosynthesis. Uses enzyme G6PDH
2. Rearrangement for glycotic intermediates: 3 unused C5 sugars converted to 2 F-6P and 1 G3P to enter glycolysis
- No ATP
- CO2 produced so irreversible
- Controlled by NADP/NADPH ratio at G6PDH enzyme
What is the point of the pentose phosphate pathway?
- NADPH production : Biosynthesis and prevent disulphide bonds forming
- C5 sugars for nucleotide synthesis: Therefore, high activity of cycle in dividing tissues, e.g bone marrow
What happens if you have a G6PDH deficiency?
Common inherited defect
- Haemolytic Anaemia
- Cataracts