Lecture 25- carbohydrate metabolism Flashcards
Glycolysis overview
Employed by all tissues for glucose oxidation to provide energy (ATP)
Anaerobic glycolysis
No oxygen or mitochondria
Pyruvate is reduced to lactate as NADH reoxidised
How is glucose transported?
Can’t diffuse so…
1. Na+ independent facilitated diffusion transport
2. ATP-dependent NA+ monosaccharide transport
Na+ independent facilitated diffusion transport
Glucose moves via concentration gradient
GLUT 1 to 14
these transports exhibit tissue-specific expression
LUT 4 is common in muscle & adipose
ATP depended NA+ monosaccharide transport system
Co-transport system
Transports glucose against a gradient
Found in intestinal epithelial cells
2 stages of conversion of glucose to pyruvate
Energy investment phase- phosphorylated form created using ATP
Energy generation phase
Location of glycolytic reactions
Phosphorylated sugar molecules don’t cross cell membranes easily
Irreversible phosphorylation of glucose traps it in cytosol and commits it
Glycolytic reaction (No.1)
Glucose phosphorylation catalysed by hexokinase in most tissues
1 of 3 regulatory enzymes of glycolysis
Low Km (high affinity for glucose)
Low Vmax means no overabundance of glucose 6-phosphate
Glucokinase (hexokinase IV)
In liver parenchymal cells/ beta cells
Higher Km so only active following consumption of carb rich meals
High Vmax allowing glucose delivered to liver to be maximally absorbed
Isomersation (No.2)
rearrangement in 3D space
Isomerisation of glucose 6-phosphate to fructose 6-phosphate
Catalysed by phosphoglucose isomerise
Rapidly reversible and not rate limiting
Another phosphorylation (No.3)
Fructose 6-phosphate phosphorylation
Irreversibe, rate limiting, catalysed by phosphofructokinase-1
The most important control point
Hight [ATP]=inhibition
High [AMP]=activation
Also inhibited by citrate
Fructose 1,6-bisphosphate cleavage (No. 4&5)
Broken into two
Aldolase cleaves fructose 1,6-bisphosphate to DHAP & glyceraldehyde 3-phosphate
Reversible & unregulated reaction
Reaction No.6 & No.7
The 1st oxidation-reduction reaction of glycolysis
No.7- Synthesis of 3-phosphoglycerate, produces ATP
Catalysed by the physiologically reversible enzyme
Reaction No.8
Phosphoglycerate mutate shifts the phosphate from carbon 3 to 2- reversible reaction
Reaction No.9
Enolase then desistributes the energy within the molecule by dehydration- reversible, high energy intermediate
Reaction No.10
Pyruvate formation linked to ATP production- catalysed by pyruvate kinase
haemolytic anemia
Mature red blood cells lack mitochondria
Dependent on glycolysis for ATP generation
Fuel ion pumps to maintain shape
Failure to generate ATP
Genetic defects of glycolytic enzymes lead to homiletic anaemia
Pyruvate fate
Reduced to lactate by lactate dehydrogenase- final product of anaerobic glycolysis
May be:
Oxidative decarboxylated into Acetyl CoA (pyruvate dehydrogenase)
Carboxylated to oxaloacetate (pyruvate carboxylase)
Reduced to ethanol
The tricarboxylic acid cycle
End point for oxidadative pathways
many roles: oxidative catabolism of carbohydrates, amino acids and fatty acids converge
Located in mitochondria
Allows oxidation of NADH & FADH₂ requires O₂
Before TCA reactions…
Pyruvate must enter mitochondria from cytosol by transporter
Then converted to acetyl CoA by pyruvate dehydrogenase complex
Leigh syndrome
Mutations in PDH complex
TCA reaction 1
Oxaloacetate is condensed with an acetyl group from acetyl CoA
Citrate is synthesised by citrate synthase
TCA reaction 2
Citrate is isomerised (isocitrate) by aconitase
TCA rection 3
Isocitrate is oxidised & decarboxylated by isocitrate dehydrogenase
Irreversible decarboxylation (rate-limiting)
Yields NADH
Releases CO₂
TCA reaction 4
α-ketogluterate is oxidatively decarboxylated by α-ketogluterare dehydrogenase complex
Produces second NADh & CO₂
TCA reaction 5
Succinylcholine Coenzyme A is cleaved at the high-energy thirster bond by succinate thiokinase
GTP is convertible with ATP
TCA reaction 6
Succinate is oxidised to numerate by succinate dehydrogenase as FAD is reduced
TCA reaction 7
Fumerate is hydrated to malate by fumerase
Reversible reaction
TCA reaction 8
Malate is oxidised to oxaloacetate by malate dehydrogenase
Produces final NADH
ΔG⁰ is endergonic but citrate synthase reaction is very exergonic
TCA output
2 CO₂
3NADH
1FADH₂
GTP
TCA regulation
Controlled by enzymes:
citrate synthase
isocitrate dehydrogenase
α-ketogluterate dehydrogenase complex
