Lecture 25- carbohydrate metabolism Flashcards

1
Q

Glycolysis overview

A

Employed by all tissues for glucose oxidation to provide energy (ATP)

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2
Q

Anaerobic glycolysis

A

No oxygen or mitochondria
Pyruvate is reduced to lactate as NADH reoxidised

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3
Q

How is glucose transported?

A

Can’t diffuse so…
1. Na+ independent facilitated diffusion transport
2. ATP-dependent NA+ monosaccharide transport

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4
Q

Na+ independent facilitated diffusion transport

A

Glucose moves via concentration gradient
GLUT 1 to 14
these transports exhibit tissue-specific expression
LUT 4 is common in muscle & adipose

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5
Q

ATP depended NA+ monosaccharide transport system

A

Co-transport system
Transports glucose against a gradient
Found in intestinal epithelial cells

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6
Q

2 stages of conversion of glucose to pyruvate

A

Energy investment phase- phosphorylated form created using ATP
Energy generation phase

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7
Q

Location of glycolytic reactions

A

Phosphorylated sugar molecules don’t cross cell membranes easily
Irreversible phosphorylation of glucose traps it in cytosol and commits it

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8
Q

Glycolytic reaction (No.1)

A

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

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9
Q

Glucokinase (hexokinase IV)

A

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

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10
Q

Isomersation (No.2)

A

rearrangement in 3D space
Isomerisation of glucose 6-phosphate to fructose 6-phosphate
Catalysed by phosphoglucose isomerise
Rapidly reversible and not rate limiting

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11
Q

Another phosphorylation (No.3)

A

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

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12
Q

Fructose 1,6-bisphosphate cleavage (No. 4&5)

A

Broken into two
Aldolase cleaves fructose 1,6-bisphosphate to DHAP & glyceraldehyde 3-phosphate
Reversible & unregulated reaction

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13
Q

Reaction No.6 & No.7

A

The 1st oxidation-reduction reaction of glycolysis
No.7- Synthesis of 3-phosphoglycerate, produces ATP
Catalysed by the physiologically reversible enzyme

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14
Q

Reaction No.8

A

Phosphoglycerate mutate shifts the phosphate from carbon 3 to 2- reversible reaction

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15
Q

Reaction No.9

A

Enolase then desistributes the energy within the molecule by dehydration- reversible, high energy intermediate

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16
Q

Reaction No.10

A

Pyruvate formation linked to ATP production- catalysed by pyruvate kinase

17
Q

haemolytic anemia

A

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

18
Q

Pyruvate fate

A

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

19
Q

The tricarboxylic acid cycle

A

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

20
Q

Before TCA reactions…

A

Pyruvate must enter mitochondria from cytosol by transporter
Then converted to acetyl CoA by pyruvate dehydrogenase complex

21
Q

Leigh syndrome

A

Mutations in PDH complex

22
Q

TCA reaction 1

A

Oxaloacetate is condensed with an acetyl group from acetyl CoA
Citrate is synthesised by citrate synthase

23
Q

TCA reaction 2

A

Citrate is isomerised (isocitrate) by aconitase

24
Q

TCA rection 3

A

Isocitrate is oxidised & decarboxylated by isocitrate dehydrogenase
Irreversible decarboxylation (rate-limiting)
Yields NADH
Releases CO₂

25
Q

TCA reaction 4

A

α-ketogluterate is oxidatively decarboxylated by α-ketogluterare dehydrogenase complex
Produces second NADh & CO₂

26
Q

TCA reaction 5

A

Succinylcholine Coenzyme A is cleaved at the high-energy thirster bond by succinate thiokinase
GTP is convertible with ATP

27
Q

TCA reaction 6

A

Succinate is oxidised to numerate by succinate dehydrogenase as FAD is reduced

28
Q

TCA reaction 7

A

Fumerate is hydrated to malate by fumerase
Reversible reaction

29
Q

TCA reaction 8

A

Malate is oxidised to oxaloacetate by malate dehydrogenase
Produces final NADH
ΔG⁰ is endergonic but citrate synthase reaction is very exergonic

30
Q

TCA output

A

2 CO₂
3NADH
1FADH₂
GTP

31
Q

TCA regulation

A

Controlled by enzymes:
citrate synthase
isocitrate dehydrogenase
α-ketogluterate dehydrogenase complex