Lecture 1 Glycolysis Flashcards

1
Q

What is AMP

A

AMP + P -> ADP, ADP + P = ATP

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2
Q

What is creatine phosphate

A

its high energy molecule stored in muscles used in the rapid production of ATP in times of high energy demand. creatine in the body makes creatine phosphate

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3
Q

Why is glycolysis a core metabolic pathway

A
  • Provides rapid energy in times of no oxygen
  • acts as intermediate for other processes
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4
Q

How should glycolysis enzymes balance?

A

Balance between energy needs of the cell and making precursors for other processes?

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5
Q

When should glycolysis be turned on and off?

A

To make other precursors?
- Not enough precursors: make more
- Enough precursors: glycolysis can slow down

Energy:
Low energy -> more glycolysis
AMP is the low energy status
ATP is the high energy status

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6
Q

What is the negative and postive control of regulatory step in step 1?

A

Negative regulator: Glucose 6-P (negative feedback)

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7
Q

What is the negative and postive control of regulatory step in step 3? Frutose-6-P -> Frutose 1-6 bisphosphate?

A

(+): F-2,6-BP
(+): AMP
(-): ATP
(-): Citrate
(-): H+

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8
Q

What is the negative and postive control of regulatory step in step 10? phosphoenol pyruvate -> pyruvate?

A

(+): F-1,6-BP (feedforward)
(-): ATP
(-): Alanine

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9
Q

How do regulators of control point affect the enzyme?

A

It affects the enzyme kinetics - making the reaction go slower or faster.

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10
Q

How do different tissues control the pathway differently?

A

Different tissues control the pathway in different ways

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11
Q

How is glycolysis in the muscles regulated?

How is phosphofructokinase regulated?
How is hexokinase regulated?
How is pyruvate kinase regulated?

A

It is regulated to meet energy needs.
Primary regulation is by ATP/AMP ratiods
Energy needs change rapidly

  • PFK is regulated by ATP and AMP
  • Hexokinase is regulated by negative feedback
  • Pyruvate kinase is regulated by ATP and feedforward activation
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12
Q

How is PFK controlled?

A

ATP and AMP compete for binding to the regulatory site

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13
Q

How does ATP/AMP binding affect PFK?

A
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14
Q

Glycolysis in muscles is tightly linked to

A

The need for ATP

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15
Q

When does Glycogen enter glycolysis

A

via Glucose-6-p

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16
Q

How is glycolysis in the liver regulated? How is PFK, Hexokinase/glycokinase regulatoed, pyruvate kninase

A

The Liver has more diverse biochemical functins than the muscle (detoxification, maintianing blood-glucose).

PFK, in addtion to ATP, is regulated by intermediates of other pathways.

Hexokinase and glucokinase (isoenzymes)

Pyruvate kinase in the liver is regulated allosterically and by covalent modification.

Regulation by metabolic intermedites, as well as hormonal regulation

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17
Q

How is glycolsyis in the liver regulated?

A

by other metabolic intermediates/hormal

18
Q

How is PFK regulated via ATP/AMP?

A

Allosteric binding

19
Q

Why does glycolsyis in liver control need to override ATP regulation?

A

Because it doesnt experience sudden changes in ATP/ADP

20
Q

How is pyruvate kinase regulation different in muscles vs. liver

A

pyruvate is regulated by ATP/AMP (allosteric). in the liver, it is also phosphorylated

20
Q

Difference between hexokinase and glucokinase

21
Q

Difference between Glucagon and Glycogen

A

Glucagon: is the hormone

Glycogen: stored sugar

22
Q

When is glucagon/insulin acgivated

A

Glucagon is activated when blood sugar is low. Liver releases glucose (from glycogen)

insulin is triggered when blood sugar is high. Triggers cells to Absorb some of the glucose from the blood. In the liver (glucose -> glycogen)

23
Q

How is PFK regulated in the liver

A

Liver: does not respond to ATP quickly -> regulate by metabolic intermeidates

Citrate (-): indicate we have enough precursors -> slows down glycolysis

F-2,6-BP (+): production of F-1,6-BP -> signals theres sugar in the blood -> glucose should speed up

24
Q

Write the full equation for glycoslysis

25
Q

What is Vmax

A

Maximum velocity of a reaction

26
Q

What is Km?

A

COncentration of substrate that permits an enzyme to achieve half of its Vmax. Its a measure of affinity. The higher the Km, the lower the affinity

27
Q

What does higher Km mean?

A

Lower affinity

28
Q

How is PFK regulated in the muscles

A

By allosteric modification of ATP/AMP.

High ATP -> ATP binds (reduces affinity of PFK for Fructose-6-P) _> slows down glycolysis

Low ATP -> AMP binds, does not inhibit -> displaccces ATP from binding -> speeds glycolysis up (cells need energy)

29
Q

How is hexokinase regulated in the muscles

A

Glucose-6-p (negative feedback)
so when glucose-6-p goes up -> slows down HK

30
Q

Pyruvate Kinase

A

(+) F-6-P -> activiates PK -> speeds glycolysis
(-) ATP -> slows down glycoslys

31
Q

What happens after a carbohydrate rich meal?

A

Glucose levels go up -> F-2,6-BP signals go up -»> push glycolysis.

But when theres a lot -> citrate build up -> (-) glycolysis

32
Q

How is pyruvate kinase in the liver regulated?

A

By phosphorylation.

So when glucose levels in the blood are low -> want to stop glycoslysi so brain can use it.

Phosphorylate the Pyruvate kynase -> slows down activity.

when glucose levels are high -> can phosphorylate it to speed up activyt

It is also regulated allostericall

33
Q

What is glucokinase? What is it responsible for? When is it active?

A

An isomer of hexokinase, mainly responsible for phosphorylating glucose in the liver. Active whne glucose levles are high

34
Q

Glucokinase vs. Hexokinase

A
  • Glucokinase has lower affinity than Hexokinase (only active at high concentrations of glucose)
  • GK has high specificity for glucose
  • Glucose is not inhibited by Glu-6-pi

When conc of Glu in the blood is high, having glucokinase in the liver can help remove the sugar from the blood and channeled into the liver

35
Q

Application of glucokinase/pharmaceutical-wise?

A

Allosteric enzymes which can increase affinity of glucokinase to help remove sugar from blood

36
Q

Are glucokinase/hexokinase allosteric enzymes?

37
Q

SLide 63

38
Q

How do hormones: glucagon and insulin coordinate metabolic pathways?

A

Insulin (pancreas): when blood sugar levels are high -> signals cells to absorb sugar frm the blood.
Liver: glucose -> glycogen

Glucagon (pancrease): when blood sugar levels are low ->secretes glucose. Liver: glycogen -> glucose

39
Q

How to control a regulatory step?

A

1.Amount of enzymes
Can be controlled by gene expression,
protein degradation, etc.
2. Enzyme catalytic activities
Allosteric control, reversible covalent
modification, hormonal regulation,
energy status of the cell.
3. Substrate availability and accessibility
Tissue, cellular compartment

40
Q

What is a regulatory step?

A

Rate determining step
Not reversible
first step that commits the flux into a psathay