Carbohydrates, Glycolysis and Gluconeogenesis Flashcards

1
Q

Describe carbohydrates AND how they are used by the body (functions)!

A
  • “hydrates of carbon”
  • they all have the same basic formula (monosaccharides); isomers provide the variation from the simple formula
  • two monosaccharides are connected through glycosidic bonds (ether bonds)

Functions:
- SOURCE of energy and STORE of energy
- glucose storage molecules; glycogen (mammals), starch (plants), cellulose
- component of mammal cell membranes (e.g ur blood type shows what carbs are present)
- cell wall component in bacteria,
- cellulose in plants
- insect exoskeleton

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2
Q

What is the structure of monosaccharides?

A
  • CH2O
  • can be aldoses or ketoses
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3
Q

What is the bond that joins monosaccharides to form larger molecules?

A

Glycosidic bonds (ether bond between the two sugar molecules)

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4
Q

Glycogen, starch and cellulose and what type of bond is present?

A

All glucose storage molecules

Glycogen in mammals. Starch in plants. Both have alpha-1,4 glycosidic bonds.

Cellulose has B-1,4 glycosidic bonds. We lack enzyme to break these thus fibre pass through undigested.

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5
Q

Describe the process of carbohydrate digestion.

A

Large ones must be broken down to be absorbed.

Starts in the mouth with salivary a-amylase which cuts up the 1,4-glycosidic bonds to make smaller molecules.

Then they go into the small intestine which has disaccharide specific brush border enzymes that are MADE by pancreatic a-amylase. These include maltase, lactase, and sucrase.

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6
Q

Does amylase from the pancreas digest disaccharides?

A

No. It makes the disaccharides that do!

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7
Q

What is disaccharide intolerance in digestion + an example?

A

Disaccharide intolerance arises when one of the enzymes is not active.

Example, lactose intolerance:
- due to lack of lactase brush border cells
- lactose travels through the small intestine to large intestine where it’s instead broken down by bacteria which is what results in the uncomfort for lactose intolerant ppl

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8
Q

Where does glycolysis occur, what does it produce and what is it used in?

A

Cytoplasm

Glucose -> pyruvate

Used in all cells to provide ATP and intermediates for other pathways (energy is released)

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9
Q

Why do red blood cells rely on glycolysis?

A

They depend on glycolysis for energy bc they don’t have mitochondria

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10
Q

Glycolysis is ___________ glucose to release energy:

a) reducing
b) oxidizing

A

oxidizing

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11
Q

What is the energy generation phase and what does it produce?

A

Final 5 steps of glycolysis

Generates 4 ATP, 2 NADH and 2 molecules of pyruvate

NADH and pyruvate both can go on to be further oxidized in TCA and ETC which produces more ATP.

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12
Q

What is the energy investment phase and what is consumed in this process?

A

First 5 rxns of glycolysis

2 molecules of ATP are invested (consumed)

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13
Q

Why is NAD+ super important?

A

It’s required for glycolysis to continue

Activated carrier of electrons

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14
Q

What does anaerobic glycolysis rely on to regenerate NAD+?

A

lactic acid fermentation

(strenous exercise produces lactate because you’re outgoing anaerobic glycolysis)

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15
Q

What is the energy yield of glycolysis? Aerobic and anaerobic

A

Aerobic:
Glucose + 2Pi + (2NAD+) + 2ADP –> 2 pyruvate + 2 ATP + 2 NADH + (2H+) + 2H2O
- Net gain 2 ATP per glucose
- requires oxidation of NADH by ETC producing 3 ATPs for each NADH entering the ETC

Anaerobic:
Glucose + 2Pi + 2ADP –> 2 lactate + 2ADP + 2H2O
- Net gain of 2 ATP per glucose
- NO net production or consumption of NADH

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16
Q

What is the net production/consumption of NADH in anaerobic glycolysis?

A

NO net production or consumption of NADH

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17
Q

Describe the process of glycolysis with emphasis on the 3 key regulatory enzymes and the net energy produced by the pathway.

A

Glycolysis plays two roles:
1. degrade glucose to generate ATP
2. provide building blocks for other pathways

The rate of glycolysis is tightly controlled by 3 regulatory enzymes:
1. Hexokinase (glucokinase in the liver):
- P from ATP added to glucose to form glucose-6-phosphate
- Traps glucose in the cell (once the glucose has a P it cannot be transported out of the cell)
- hexokinase is inhibited by it’s product G-6P

  1. PFK-1
    - P from ATP is added to fructose 6-P by PFK to form fructose 1,6-bisphosphate
    - committed step for glycolysis
  2. Pyruvate kinase:
    - transfers a P from PEP to ADP, which forms ATP and pyruvate

ALL ARE IRREVERSIBLE!!! (need another enzyme in order to be reversible)

18
Q

Describe the regulation of glycolysis in muscles!

A

Since we moving theres increase in glycolysis (we need more energy!!)

The ratio of ATP/AMP indicates energy level in cells. If we have more ATP then less glycolysis is required cuz we good.

In muscles the primary role of glycolysis is to provide ATP

19
Q

What does the ratio of ATP/AMP show?

A

The ratio of ATP/AMP indicates energy level in cells. If we have more ATP then less glycolysis is required cuz we good.

20
Q

3 key regulatory enzymes in glycolysis inhibited by what? And what happens when they are?

A

PFK inhibited by high levels of ATP!!! Activated by AMP!!!

Hexokinase is inhibited by its product, G-6P. High concentrations of glucose 6-phosphate signal that the cell no longer requires glucose for energy, so no more glucose needs to be broken down. When PFK is inhibited, we have more AMP, therefore PFK inhibition also leads to hexokinase inhibition!

Pyruvate kinase is allosterically inhibited by ATP (lots of ATP = bye bye). It is activated by Fructose 1-6-bisphosphate (a product of PFK)

21
Q

Describe the regulation of glycolysis in the liver.

A

Liver is a more biochemically diverse tissue: more complex tissue leads to more complex regulation

Liver maintains blood glucose concentrations
- Stores glucose as glycogen
- Synthesizes new glucose via gluconeogenesis
- Uses glucose to make building blocks for other molecules

PFK: Regulated by ATP like the muscle, however less ATP since the liver does not experience the sudden ATP needs that a contracting muscle does, so less significant regulation

Liver also produces carbon skeletons for biosynthesis, thus availability of these molecules regulates PFK
* Citrate – first intermediate of citric acid cycle – inhibits: In the liver, phosphofructokinase is inhibited by citrate, an early intermediate in the citric acid cycle. A high level of citrate in the cytoplasm means that biosynthetic precursors are abundant, so there is no need to degrade additional glucose for this purpose. In this way, citrate enhances the inhibitory effect of ATP on phosphofructokinase.

22
Q

What are isozymes?

A

enzymes, encoded by the different genes, that catalyze the same reaction

23
Q

Why does glucose uptake into the cell membrane require a glucose transporter?

A

Glucose is hydrophilic, so it can’t cross the membrane without a glucose transporter

24
Q

IN MUSCLES
Enzyme, activated by, inhibited by?

Hexokinase, _________, ___________

PFK-1, ___________, ____________

Pyruvate kinase, __________, ___________

A

Hexokinase
Activated by:
Inhibited by: Its product (glucose 6-P)

PFK-1
Activated by: AMP
Inhibited by: high levels of ATP

Pyruvate kinase
Activated by: Fructose 1,6-bisphosphate (product of PFK)
Inhibited by: high levels of ATP

25
Q

IN LIVER
Enzyme, activated by, inhibited by?

Hexokinase, _________, ___________

PFK-1, ___________, ____________

Pyruvate kinase, __________, ___________

A

Hexokinase
Activated by:
Inhibited by: Its product (glucose 6-P)

PFK-1
Activated by: AMP
Inhibited by: high levels of ATP

Pyruvate kinase
Activated by: Fructose 1,6-bisphosphate (product of PFK)
Inhibited by: high levels of ATP

26
Q

Where does gluconeogenesis occur?

A

Mitochondria and cytoplasm of kidney and livers

Liver is most important cuz it’s responsible for blood glucose levels

27
Q

Describe gluconeogenesis and how it differs from a simple reversal of glycolysis (4 reactions).

A

Glycolysis is the first stage of extracting energy from the sugar glucose. The end result is pyruvate, which can also be produced from other simple sugars and is the fuel for the next stage, the citric acid cycle. There are eight steps in glycolysis, of them, three are irreversible: the initial phosphorylation of the sugar, a second phosphorylation (third step), and the removal of the last phosphate to yield pyruvate.

In theory gluconeogenesis is the reverse process of glycolysis, some steps are irreversible steps. Hence, it requires additional intermediate or energy.

Gluconeogenesis is the formation of glucose from pyruvate to provide energy reserves for the cell. At the three one-way points in glycolysis, gluconeogenesis involves different enzymes. The reactions are different, but two pyruvate molecules are eventually combined as glucose. The other steps are the same in reverse order; they run back and forth in either process until equilibrium is reached.

Oxaloacetate is an intermediate that is not present in the process of glycolysis, but in gluconeogenesis

28
Q

What are the contributors (beginning) of gluconeogenesis?

A

Lactic acid (from muscles)

Glycerol (from triglycerides)

Amino Acids

29
Q

What are the hormones involved in gluconeogenesis?

A

Glucagon (made by pancreatic a-cells)

Epinephrine

Cortisol

Thyroid hormone

Growth hormone

30
Q

Describe the two catalytic domains of Fructose 2-6-bisphosphate (PFK-2/FBPase 2)

A

PFK-2 (kinase domain) adds P
- Activator of PFK/glycolysis

FBPase 2 (phosphatase domain) removes P
- Inhibits glycolysis
- ACTIVATES gluconeogenesis

When one domain is active, the other is inactive

31
Q

When blood glucose is low, PFK-2 is:

a) phosphorylated and inhibited
b) phosphorylated and activated
c) dephosphorylated and activated
d) none

A

a) phosphorylated and inhibited

32
Q

Where is glycogen stored? And what is the difference in how its used for where its stored?

A

The liver and muscle

Muscle is selfish, stores it only for itself

Liver for everything else

33
Q

Describe the degradation of glycogen, what does it require, and what are the products?

A

It requires two enzymes:
1. Glycogen phosphorylase
- this cleaves a(1-4)linkages
- produces glucose 1-phosphate

  1. Debranching enzyme
    - removes the outer 3 of 4 glucose molecules from the branch to the straight chain forming a new a(1-4) bond
    - the remaining glucose is removed by another enzyme
    - Products are: Glucose 1-phosphate and glucose
34
Q

What is glycogen? (structure)

A

It is a branched chain homopolysaccharide (all glucose)

It is made up of a-D-glucose

Primary glycosidic bond is an a(1,6) linkage. This is basically when C1 is bound to C4 of the next molecule.

After 8-10 glucoses, there is a branch formed by an a(1,6) linkage. This allows for more glucose to be formed in the same amount of space and to add glucose to both ends of the molecule.

35
Q

Describe the importance of reciprocal regulation in glycolysis and gluconeogenesis.

A

If one is on, the other needs to be turned off: “reciprocal regulation”

The regulatory molecules that activate one pathway inhibit the imposing

36
Q

Describe the synthesis of glycogen.

A

Substrate: UDP-Glucose (an activated form of glucose)

Requires: 2 enzymes
1. Glycogen synthase. This catalyzes the transfer of glucose from UDP-glucose to the growing chain
2. Branching enzyme. This introduces the a(1,6) linkages. It also increases the number of active sites to bind to, speeding up the process.(

37
Q

Talk about the reciprocal regulation of glycogen synthesis and degradation.

A

An important control mechanism prevents glycogen from being synthesized at the same time it is being broken down.

The same glucagon and epinephrine triggered cAMP cascades that initiate glycogen breakdown in the liver and muscle, respectively, also shut off glycogen synthesis.

Protein phosphatase 1 reverses
the regulatory effects of kinases
on glycogen metabolism.

After exercise, muscle must shift from a glycogen degrading mode to one of glycogen replenishment. A first step in this metabolic task is to shut down the phosphorylated proteins that stimulate glycogen breakdown.

38
Q

Is it possible to have high glucose but low ATP?

A

Yes, glucose and ATP are two different types of energy. You can have high glucose and low ATP for example when you just ate and are running.

39
Q

Describe the reciprocal regulation of glycogen synthesis and degradation. Mention what each is stimulated by.

A

Synthesis is stimulated by high levels of glucose and ATP (well-fed state)

Breakdown is stimulated by low glucose and energy levels (fasted state)

Regulation of glycogen synthase (synthesis) and phosphorylase (breakdown) at two levels:
1. allosteric factors (primarily glucose 6-phosphate)
2. hormonal factors (elevated insulin levels increase glycogen synthesis, elevated glucagon increase degreadation)

40
Q

Which ones are increased in glycogen synthesis

Glucose 6-P

ATP

Insulin

Glucagon

A

Glucose 6-P: INCREASED

ATP: INCREASED

Insulin: INCREASED

Glucagon: DECREASED

41
Q

Which ones are increased in glycogen degradation

Glucose 6-P

ATP

Insulin

Glucagon

A

Glucose 6-P: DECREASED

ATP: DECREASED

Insulin: DECREASED

Glucagon: INCREASED