Lecture 2: Carbs 2 Flashcards

0
Q

Key regulation mechanisms: 4 of them

A
  1. substrate/ product (stimulation or inhibition)
  2. Km (concentration if substrate that gets you to half max) or Vmax. Good example are GLUT transporters, 1 and 3 had low infinity.
  3. allosteric effectors: is any substance that will effect the rate of activity of an enzyme by binding to it other than its active site. It changes its affinity, ie increase or decrease.
  4. covalent modulation: an enzyme that you can regulate the activity of an enzyme by phosphorylating it, you change its activity so it can work better or slower on a substrate.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q
Definitions: life will be a lot easier if you remember these 
Enzyme names: 
Kinase
Phosphorylase 
Phosphatase
A

Definitions:
Enzyme names:
Kinase eg protein kinase: so it adds a phosphate to a protein
-any enzyme that adds phosphate using ATP as the phosphate donor. Another ex, pyruvate kinase➡ adds phosphate group to pyruvate.
Phosphorylase eg glycogen phosphorylase
-any enzyme that’s adds phosphate using inorganic phosphate (Pi) as the phosphate donor. Doesn’t need ATP, just grabs it from free floating phosphates.
Phosphatase eg protein phosphatase
-any enzyme that removes phosphate as inorganic phosphate (Pi)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Glycolysis

A

Major pathways for cabo metabolism.
Function: catabolism of carbs as glucose to produce energy in form of ATP.
Unique features:
-reactions proceed through phosphorylated intermediates.
-substrate level phosphorylation
Location: it occurs in soluble cytoplasm.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When is glycolysis important for ATP production?

A

High glucose intake- very important
Stress
Exercise
Availability of glucose is a major driver for glycolysis.
When availability is high it is very important.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Tissue dependant on glycolysis

A
  1. Brain- only uses glucose
  2. Erythrocytes, rely on anaerobic glycolysis only
  3. Type 2 muscles
  4. Foetus
  5. Renal medulla
  6. Retina
  7. Skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The glycolytic pathway

A

-6 carbon substrates going in. This 6 carb goes to two 3 carb substrate.
Total energy generated:
Investment phase- 2 ATP
Pay off phase: 4 ATP
Nett: 2 ATP
Hexo(means 6) kinase (phosphorylates using ATP)
-Hexokinase phosphorylated glucose to 2 glucose-6-phosphate using ATP (phosphate added)
-phosphofructokinase make fructose 6-phosphate to fructose 1,6-biophosphatase using ATP
Etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Regulation of glycolysis

A

Regulatory steps

  • 3 parts can’t go backwards
  • they are allosterically regulated.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Hexokinase- anchors glucose

A

He phosphorylates (adds phosphate) glucose. This phosphate group makes it stay in the cell, the glucose would run away.

  • hexokinase has very low Km (high affinity enzyme for hexoses) low vmax. Slow Vmax can be a problem when you have bulk glucose! Doesn’t go fast enough to anchor the glucose.
  • found in all cells
  • controlled allosterically by product glucose 6-P
  • not specific for glucose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Glucokinase (liver in humans)

A

Km= 10 mM, higher Vmax.
It phosphorylates glucose
-specific for glucose
-not in liver of ruminants coz they have low glucose absorption.
-the additional activity of glucokinase enables liver to phosphorylate heaps of glucose to decrease glucose concentration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Phosphofructokinase

Th most important rate regulator!

A

It works on fructose-6-phosphate. Hence the fructo part of the name, and its a kinase so its going to use ATP and add a phosphate group onto it, so you end up with a fructose 1-6 biphosphate.
It’s controlled by a few things
Inhibition:
-ATP inhibits it, when glycolysis has been moving too fast. Thus ATP feeds back and slows glycolysis down by inhibiting this enzyme.
-citrate
-H+: when? After excercise, it becomes acidic and inhibits this enzyme.

Stimulators:
Fructose 2, 6-bisphosphate (single most potent effector of this enzyme) it goes in and allosterically regulates PFK1-phosphofructokinase. It is made by fructose 2,6-bisPase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pyruvate kinase:
Inhibitors
Stimulators

A
Inhibitors: 
Allosteric- ATP, alanine 
Covalent- glucagon, switches on an enzyme which adds a phosphate to pyruvate kinase, by doing that it will slow it down and inhibit it. 
-around during (low sugar) starvation
-slows down glycolysis 

Stimulation:
Allosteric: fructose 1,6-bis phosphatase (feed-foreword control)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why do you get lactic acid?

A

So you can recycle NADH so glycolysis can proceed.

There is only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Anaerobic glycolysis

Lactate dehydrogenase

A

Can make lactic acid from pyruvate and pyruvate from lactic acid. Slide ?
Essential additional enzyme for this anaerobic scenario

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Aerobic glycolysis.
Oxygen as the final electron acceptor
What enzyme enables pyruvate to be converted to acetyl coA?

A

Pyruvate can be fed into aerobic glycolysis called TCA cycle.
Pyruvate dehydrogenase catalysed this reaction. It converts pyruvate to acetyleCoA. You can reverse this step.
You can’t convert acetyleCoA back to glucose.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pyruvate dehydrogenase is regulated by?

A
  1. End product inhibition
  2. Covalent modulation
    If you have high levels of pyruvate it will slow this enzyme down
    If you have high levels of acetyleCoA you will speed this enzyme up. So will
    -NADH (like when your metabolising fat) which generates heaps of NADH, acytlecoa which switches off kinase which switches off dehydrogenase.
    -the enzyme reaction if controlled by the phosphorylation status of pyruvate dehydrogenase
    -inhibited when phosphorylated this the oxidation of acetyleCoA can’t proceed
    Look at pg 9
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How is glycolysis regulated?

A
  1. Regulatory enzymes -allosteric enzymes. Each of these regulatory enzymes is irreversible under physiological conditions
    A) PFK1- most important phosphofructokinase 1-turns fructose6-P to fructose 1,6-bisphosphate using an ATP
    Allosteric affectors affecting this enzyme.
    Negative(inhibit activity): ATP, H+ and citrate
    Positive (stimulate activity): AMP and fructose 2,6bisP (is produced by the bifunctional enzyme PFK2)

B) Pyruvate kinase (turns phosphoenolpyruvate to pyruvate)
Inhibited by: ATP, amino acid alanine
Stimulated by: fructose 1,6 bisP in feed forward mechanism
Glucagon inhibits it by phosphorylation and subsequent inhibition of pyruvate kinase.

C) Hexokinase: glucose➡ glucose 6P
-inhibited by product glucose 6P

  1. Substrate availability:
    Limiting glycolysis: glucose and NAD+
    -the supply of NAD+ is controlled through removal of the product NADH+ and H+
  2. Product removal
    - NADH+ H+ is recycles to NAD+ through action of lactate dehydrogenase during anaerobic glycolysis
31
Q

Aerobic glycolysis -essential for the brain and nervous tissue. The production of ATP through aerobic glycolysis proceeds through the irreversible mitochondrial enzyme _____

A

Pyruvate dehydrogenase
The enzyme reaction is controlled by the phosphorylation status of pyruvate dehydrogenase which is inhibited when phosphorylated. Therefore the oxidation of pyruvate to AcetyleCoA Can’t proceed.
2 regulatory enzymes:
1. Pyruvate dehydrogenase kinase-phosphorylates it
-positive activator
ATP, acetyleCoA and NADH
Negative inhibitor: Ca2+
2. Pyruvate dehydrogenase phosphatase- removes phosphate group
Positive: Ca2+,’ Mg2+ and insulin

Therefore the controls of this step is linked to the energy supply and demand of the cell