Glycolysis (Catabolism of Glucose) Flashcards

1
Q

What is metabolism?

A

All chemical reactions that maintain the living state of cells and organisms

Anabolism + Catabolism

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2
Q

Define anabolism

A

Assimilation of molecules and complex structures from building blocks of life

Requires energy

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3
Q

Define catabolism

A

Breakdown of molecules to obtain the anabolic building blocks of life and substrates for energy

Yields energy

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4
Q

Where does out energy come from?***

A

From the sun

Plants photosynthesise macromolecules using sunlight as energy

Catabolic pathways oxidise macromolecules, creating ATP

ATP can be used to drive biosynthesic reactions

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5
Q

What are the redox reactions that take place in metabolism? ***

A
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6
Q

What cells types require glucose as an energy source?

A

Erythrocytes
Retina
Renal Medulla
Brain
All cancer cells (Warburg Effect)

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7
Q

Name 4 disaccharides

A

Lactose

Maltose

Sucrose

Cellobiose

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8
Q

What is the lactose bond?

A

galactose beta-1,4 glucose

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9
Q

What is the maltose bond?

A

glucose alpha–1,4 glucose

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10
Q

Sucrose

A

glucose alpha-1,2 fructose

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11
Q

What is the cellobiose bond?

A

glucose beta-1,4 glucose

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12
Q

What are the 4 fates of glucose?

A

Storage (glycogen, starch, surcose, conversion to LIPIDS)

Pyruvate by oxidation via aerobic glycolysis

Lactate by fermentation via anaerobic glycolysis

Ribose-5-P by oxidation through Pentose Phosphate Pathway

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13
Q

What is pyruvate needed for?

A

Effieicnt ATp production by oxidative metabolism

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14
Q

What is lactate needed for?

A

Rapid, inefficient ATP production

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15
Q

What is ribose-5-P needed for?

A

Precursor for nucleotide synthesis & DNA repair

Essential for growth

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16
Q

What are the intracellular stages of metabolism?*

A

Acetyl-CoA production

Acetyl-CoA oxidation

Electron transfer & oxidative phsophorylation

17
Q

How is glucose transported into cells?

A

Via Na+/glucose symporters
AND
Via passive facilitated diffusion glucose transporters (GLUT)

18
Q

What does low Km mean?

A

High affinity for glucose

19
Q

Where is GLUT1 found and what is it’s Km?

A

Brain
Low KM

Same as GLUT3

20
Q

Where is GLUT2 found and what is it’s Km?

A

Liver and beta-cells (pancreas)

High KM

Insulin-independent

21
Q

Where is GLUT3 found and what is it’s Km?

A

Brain
Low KM

Same as GLUT1

22
Q

Where is GLUT4 found?

A

Muscle & adipose

Insulin-indpendent

23
Q

What is GLUT5 and where is it found?

A

Fructose transport in GUT

24
Q

What are the 3 control points and why?

A

Enzymes catalyzing irreversible reactions

Hexokinase = substrate entry

Phosphofructokinase = rate of flow

Pyruvate Kinase = product exit

25
Q

What inhibits the 3 control points?

A

Hexokinase = product inhibition (G6P)

Phosphofuctokinase = ATP (shows enough energy already)

Pyruvate kinase = product inhibition (ATP)

26
Q

What is phosphofuctosekinase regulated by?

A

Activators = AMP and fructose-2,6-BP

Inhibitors = ATP, H+, citrate

27
Q

Why are AMP and fructose-2,6-BP activators of phosphofructokinase?

A

Increase glycolysis if energy is needed

28
Q

Why are ATP, H+, citrate inhibtors?

A

ATP will slow glycolysis if energy is abundant

H+ slows glycolysis if too much lactic acid

Citrate slows downstream pyruvate entry into TCA if energy is abundant

29
Q

What is energy charge?

A

ATP/AMP ratio = controls phosphofructokinase

30
Q

What does the cell being fully charged vs discharged mean?

A

Fully charged = all adenylate nucleotides are ATP

Discharged if the cell only has AMP and Pi

31
Q

What happen if mitochondrial metabolism is inhibited by lack of oxygen?

A

NADH is used to ferment pyruvate to lactate

NADH is regenerated by G3P dehydrogenase (start of stage 3)

32
Q

When is NADH regenerated?

A

NADH is regenerated by G3P dehydrogenase (start of stage 3)

33
Q

What is the Warburg Effect?

A

Upregulation of anaerobic glycolysis in cancer cells

34
Q

How do cancer cels produce energy?

A

ANAEROBIC glycolysis

High rate of GLUCOSE to LACTATE

35
Q

What relationship do cancer cells have with hexokinase?

A

Cancer cells have low KM hexokinase meaning they have HIGH affinity for glucose

36
Q

What are the advantages for anaerobic glycolysis in cancer cells?

A

Rapid energy production

Supports other pathways for nucleotide sythesis (needed for growth)

Supports rapid cell proliferation

37
Q

What are the disadvantages for anaerobic glycolysis in cancer cells?

A

Produces H+ and lactate

Very inefficient ATP synthesis

High glucose comsumption demand

Cancer patients lose weight

38
Q

How are they treating cancer by targeting glycolysis?

A

Competitive inhibtors

2-deoxy-glucose = blocks further metabolism of G6P

3-bromopyruvate = block production of 1,3-bisphosphoglycerate

AND

Dichloroacetate = promotes conversion of lactic acid to pyruvate

39
Q

How does dichloroacetate work? ***

A

Inhibits pyruvate dehydrogenase kinase

Promotes conversion of lactic acid to pyruvate

By re-engageing mitochondrial metabolism = slows glycolytic rate

Cells can no longer sustain nucleotide synthesis and so cannot grow