Glycolysis Flashcards

1
Q

What does glycolysis break down and produce?

A

Breaks down glucose and fructose to pyruvate

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2
Q

What happens to glycolysis when lacking oxygen, like ischemia?

A

Glycolysis persists because it does not require oxygen

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3
Q

Along with pyruvate, what does glycolysis produce per glucose?

A

2 ATP and 2NADH

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4
Q

What are the four steps in glycolysis?

A
  1. Hexokinase/Glucokinase
  2. Phosphofructokinase I
  3. GAPDH; PGK
  4. Pyruvate kinase
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5
Q

What is glycolysis most important for? Why?

A

Red blood cells - no mitochondria

Brain - can’t use fatty acids

Anaerobic environments - exercising muscles

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6
Q

What are other energy pathways besides glycolysis?

A

Mitochondrial fatty acid oxidation

Amino acid catabolism

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7
Q

Where does glycolysis occur?

A

Cytosol

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8
Q

What will a patient with a glycolytic disorder present with? Why?

A
  1. Hemolytic anemia - lysis of red blood cells
  2. Jaundice - degradation of hemoglobin released from red blood cells
  3. Enlarged spleen - removal of damaged RBCs
  4. Rare congenital disorders - pyruvate kinase deficiency

Why? Red blood cells rely exclusively on glycolysis

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9
Q

What steps of glycolysis require energy to be put in?

A

Hexokinase/Glucokinase converting glucose to glucose-6-phosphate

Phosphofructokinase I converting fructose 6-phosphate to fructose 1,6-bisphosphate

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10
Q

What steps of glycolysis create energy?

A

GAPDH converting glyceraldehyde 3P to 2 bisphosphoglycerate

2 bisphosphoglycerate being converted to 2 phosphoenolpyruvate by PGK

2 phosphoenolpyruvate to 2 pyruvate by pyruvate kinase

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11
Q

What regulates glycolysis?

A

Glucose availability and energy demand

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12
Q

When is glycolysis most active?

A

Glucose conc in blood high - high insulin/glucagon ration

Low energy - low ATP/AMP ratio

Unsaturated mitochondria - low citrate

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13
Q

What are the key regulatory points of glycolysis and why?

A

Hexokinase - entry of glucose

Phosphofructokinase I - committed step

Pyruvate kinase - exit point, entry to mitochondria

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14
Q

What is the main regulated step of glycolysis? What regulates it? x3

A

Phosphofructokinase I

3 main signals:
1. citrate - mitochondrial overload, repressor

  1. Insulin and glucagon - nutritional state via cAMP and F2,6BP
  2. ATP and AMP - energy state, repressed by high ATP
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15
Q

What signal integration goes through fructose 2,6 - bisphosphate?

A

Signals: insulin, glucagon, AMP, fructose 6P

No other function than to stimulate glucose catabolism

High F2,6 BP means high glucose catabolism

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16
Q

What step in glycolysis is often upregulated in cancer?

A

PFK II because it produces fructose 2,6 bisphosphate which stimulates glucose catabolism

17
Q

How does cAMP regulate carbohydrate metabolism?

A

Glucagon - low blood glucose - signals cAMP

cAMP activates PKA to produce glucose by reducing glucose consumption and increasing glucose production

18
Q

Glucose consumption

A

Increased glycolysis and increased glucose storage

19
Q

Glucose production

A

Increased gluconeogenesis and increased mobilization of glucose from storage

20
Q

What is a hallmark of starvation? How does this relate to insulin?

A

Phophorylation of metabolic enzymes to boost blood glucose

Insulin dephosphorylates to indicated well-fed state

21
Q

How does PGK and pyruvate kinase produce ATP?

A

Substrate level phosphorylation

22
Q

What does glyceraldehyde 3P dehydrogenase produce? What happens to that product?

A

NADH! Oxidized to NAD to continue glycolysis

23
Q

What activates and inhibits pyruvate kinase?

A

Activated by insulin and fructose 1,6-bisphosphate

Inhibited by ATP

24
Q

What are inherited errors of metabolism and what do they involve?

A

IEM are mutations in the genes that code for enzymes for glycolytic degradation. These enzymes are required by galactose and fructose.

Disorders are present at birth and manifest upon ingestion of substance

Impeded development and can cause disability

25
Q

How does fructose degradation differ between muscles and the liver?

A

Fructose in muscle –> Hexokinase yields F6P and is slow. Goes through normal glycolysis

Fructose in liver is degraded fast by fructokinase to yield F1P. Aldolase B is then required to cleave F1P so it can enter glycolysis

26
Q

How does fructose metabolism work in relation to insulin?

A

Fructose metabolism occurs in the liver and does not trigger insulin release. Not dependent on insulin. Blood fructose does not signal fed state

27
Q

Fructokinase deficiency, no accumulation of fructose in cells and fructose is excreted in urine, benign.

A

Essential fructosuria

28
Q

Hereditary Fructose Intolerance. What occurs? How to treat?

A

Aldolase B deficiency

Fructose-P accumulation in liver, which depletes liver phosphate pools and impairs glycogen mobilization - leads to hypoglycemia

Liver damage - accumulation of glycogen, lack of Pi –> jaundice

Treat by avoiding fructose and sucrose

29
Q

What enzymes degrade galactose to glucose?

A

Galactokinase

Galactose uridyltransferase

Epimerase

30
Q

What has to happen to galactose to become glucose?

A

Has to become a UDP-bound galactose

31
Q

Galactosemia. What are the possible causes? What do patients present with?

A

Galactose-1-phosphate uridyl transferase deficency – galactose P accumulates

UDP-galactose epimerase deficiency

Galactokinase deficiency

Newborns present with milk intolerance and sign of liver failure (jaundice)

32
Q

What happens to NADH during and after glycolysis?

A

Re-oxidized to NAD during glycolysis

Lactase dehydrogenase produce lactate with oxidation of NADH

Lactate oxidized back to pyruvate, liver converts lactate to glucose, brain can use lactate for energy

NADH can be used to shuttle electrons into mitochondria

33
Q

Cori Cycle

A

Lactate taken up by liver and converted to pyruvate

Pyruvate converted back to glucose

34
Q

Mitochondrial Shuttles

A

Glycerol phosphate shuttle - muscle and brain, oxidize NADH, reduce FAD –> FADH

Malate/Aspartate shuttle - liver and heart, efficient, oxidize NADH and then reduce NAD to –> mitosolic NADH