PHR912 Carbohydrate Metabolism 2

What is the universal fuel?

Glucose

Glycolysis can occur in every what?

Cell type

Where does glycolysis occur?

Cytosol

Does glycolysis involve O2?

NO

What kind of phosphate intermediates does glycolysis prodvide?

High energy phosphate intermediates

What does glycolysis produce?

• 2 ATP

• 2NADH/H

  • Pyruvate

In anaerobic cells, what does pyruvate get reduced to?

Lactate to regenerate NADH

How much ATP is generated in the anaerobic pathway of glycolysis?

2 ATP per mol glucose

What are some anerobic conditions where glycolysis will take place?

RBC and muscles under heavy stress and exercise and in cancer cells

What can provide a precursor for lipid biosynthesis in liver and adipose tissue?

Glycolysis

What regulates glycolysis in the liver and adipose tissue?

Insulin and glucagon

Glycolysis provides precursors to what molecules?

Amino acids: 5 carbon sugars

Pentoses: pentose phosphate pathway

What is the preparative phase of glycolysis:

Glycose → Fructose-1,6-Bisphosphate

How much ATP gets consumed during the preparative phase?

2 ATP

What is the ATP-generating phase of glycolysis?

Triosephosphates to pyurvate

All intermediates between glucose and pyruvate are what?

Phosphorylated

Dihydroxyacetone phosphate can lead to the synthesis of what?

Backbone of lipids

Kinases do what?

Phosphorylating enzymes

Kinases use what for the energy and phosphate source?

ATP

What is the first step of glycolysis?

Glucose → Glucose-6-Phosphate

What catalyzes the first reaction of glycolysis?

First reaction:

Hexokinase (Glucokinase)

Which OH is the most reactive group in glucose?

The 6-position

What is the 3rd enzyme of the glycolytic pathway?

Phosphofructokinase

What reaction does phosphofructokinase catalyze?

Fructose-6-phosphate → fructose-1,6-bisphosphate

What is the rate limiting step of glycolysis?

Phosphofructokinase

What are the ATP-generating phases of glycolysis?

From fructose-1,6-bisphosphate (FBP) → Pyruvate

What does pyruvate kinase catalyze?

PEP → Pyruvate

What does glycolysis begin with?

Glucose

What does glycolysis end with?

Pyruvate

Some intermediates of glycolysis are highly energetic and can generate what through substrate level phosphorylation.

ATP

In addition to ATP, what else can get produced?

NADH

How much NADH/H gets produced in glycolysis?

2

What does the reduced form of NADH carry?

2 protons + 2 electrons

How much energy equivalent of ATP does NADH have?

3 ATP

What does NAD stand for?

Nicotineamide-Adenine-Diuncleotide

Aerobic metabolism of each glucsose molecule yields how much ATP?

36-38

How do the reduced co-factors reach the inner mitochondria?

Shuttle SystemsW

What are the shuttle systems in glycolysis?

Malate-Aspartate Shuttle

Glycerol-3-P shuttle

If both NADH molecules generated in glycolysis are

shuttled into the mitochondrial matrix via the glycerol-3-P

shuttle, how many ATPs are generated in the aerobic

breakdown of glucose (glycolysis/TCA/ETC)?

36

What is the main job of the pryuvate dehydrogenase complex?

The link between glycolysis and TCA cycle.

Converting pyruvate into acetyl-CoA

Where is the PDH located?

Mitochondrial matrix

How much NADH does the PDH yield per pyruvate molecule?

1

How many subunits are in the PDH?

3 subunits

What special transporter brings pyruvate into the mitochondrial membranes for the PDH complex?

Pyruvate/H+-symporter

The PDH is overall what kind of reaction?

Oxidation

How many co-enzymes of PDH?

5

What does co-enzyme Thiamine Pyrophosphate do in the PDH complex?

Binds the aldehyde generated from the decarboxylation of pyruvate

What does co-enzyme Lipoic Acid do in the PDH complex?

Acts as transferring crane arm between TPP and co-enzyme A

Transfering the acetyl-residue from TPP to co-enzyme A

Generates energy in form of NADH/H and the reactive acetyl-CoA

What does co-enzyme FAD do in the PDH complex?

Takes over the 2H+ and 2 electrons from dihydroliopic acid

What does co-enzyme NAD do in PDH?

Takes over the 2H+ and 2 electrons from the previous FAD enzyme

What does co-enzyme A do in the PDH?

Forms the final energy-rich thioester bond with the product of the reaction, to become acetyl-CoA.

This participates in 100s reactions in cells

Pantothenate is what vitamin?

B5

What vitamin is thiamine?

Vitamin B1

What vitamin is riboflavin?

B2

What vitamin is Niacin?

B3

What co-enzyme comes from Pantothenate?

Co-enzyme A

What co-enzyme comes from thiamine?

Thiamine-PP

What is the co-enzyme from Riboflavin?

NAD+

What is the co-enzyme from Niacin?

NAD+

Does lipoic acid have a water-soluble enzyme?

NO

Where does lipoic acid get biosynthesized?

In our cells.

What are the correct sequences of co-factor involvement in the PDH and alpha-ketoglutarate DH complexes?

TPP → Lipoic acid → FAD → NAD → CoA

TPP → Lipoic acid → CoA → FAD → NAD

During anaerobic metabolism, NADH generated by glycolysis is re-oxidized by what enzyme to produce lactic acid?

Lactate dehydrogenase

What is the ONLY way RBC (erythrocytes) generate energy?

Anaerobic glycolysis producing 2 ATP

Under anaerobic metabolism of yeast, what does NADH generated by glycolysis get re-oxidized by?

Alcohol dehydrogenase

What is the intermediate pathway of anaerobic metabolism of yeast?

Pyruvic Acid → Acetaldehyde → Ethanol

What enzyme catalyzes the conversion of pyruvic acid to acetaldehyde in the anaerobic metabolism of yeast?

Pyruvate decarboxylase

What enzyme catalyzes the conversion of acetaldehyde to ethanol in the anaerobic metabolism of yeast?

alcohol dehydrogenase

What is the Cori-Cycle:

Cooperation between aerobic and anaerobic cells

How many points of regulation does glycolysis have?

4

Wht is the first point of regulation in glycolysis?

Glucokinase (Hexokinase)

What is the second point of regulation in glycolysis?

PFK-1

PFK-2

What is the 3rd point of regulation in glycolysis?

Pyruvate Kinase

What is the 4th point of regulation in glycolysis?

Pyruvate Dehydrogenase Complex

Why is hexokinase a good regulator of glycolysis?

The high K_M cannot support the reverse reaction of hexokinase

When is hexokinase the most active?

After meals, when glucose levels are high during the fed state

What is hexokinase induced by?

Insulin

What does PFK-1 cooperate with?

PFK-2

What does PFK-1 + PFK-2 synthesize together?

fructose-2,6-bisphosphate

What is PFK-1 ALLOSTERICALLY inhibited by?

ATP

Citrate

What is PFK-1 ALLOSTERICALLY stimulated by?

AMP

ADP

Fructose-2,6-bisphosphate

What triggers the stimulation of Pyruvate Kinase?

Insulin

Fructose-1,6-bisphosphate

What inhibits the sitmulation of pyruvate kinase?

Glucagon

Alanine

ATP

What does insulin do to Pyruvate Kinase?

Removes the phosphate from the pyruvate kinase

the dephosphorylated enzyme is now active

Glycolysis is induced

What does glucagon do to pyruvate kinase?

Triggers the phosphorylation of pyruvate kinase

The phosphorylated enzyme is inactive

Glycoloysis gets inhibited

What reaction does pyruvate kinase facilitate?

PEP → Pyruvate

Which enzymes involved in aerobic glucose breadkwon are alloserically controlled?

PFK-1

PDH

Pyruvate Kinase

Which enzymes of aerobic glucose breadown are hormonally (insulin/glucagon) controlled?

Pyruvate kinase and PDH

The heart muscle uses considerable amounts of lactate for what?

Energy

How does the body remove excess lactate from the body to prevent lactic acidosis?

The heart using up lactate

A major role of glycolysis is which of the following?

To produce energy

Starting with glyceraldehyde-3-phosphate and synthesizing one molecule of pytruvate, the net yield of ATP and NADH would be what?

2 ATP

1NADH

When glycogen is degraded, glucose 1-phosphate is formed. Glucose 1-phosphate can then be isomerized to glycose-6-phosphate. Starting with glucose 1-phosphate and ending with 2 molecules of pyruvate, what is the net yield of glycolysis in terms of ATP and NADH formed?

3 ATP, 2 NADH

Which of the following statements correctly describes an aspect of glycolysis?

Two molecules of ATP are used in the beginning pathway.

How many mols of ATP are generated by the complete aerobic oxidation of 1 mol of glucose to 6 mol of CO2?

30-32 because it has gone through the TCA chain to produce CO2