Download pdf - Glycolysis and Gluconeogenesis - كلية الطب...Page 3 Glycolysis and Gluconeogenesis اهايحأ نم و 6166/6102 Glucose is not found free in our muscle but its stored as

neogenesisGlycolysis and Gluco

الفريق الطبي األكاديمي

لكــية الطب البرشي

البلقاء التطبيقية / املركز

6102/6166أ حياها و من

Done By :- Renad Aburumman

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neogenesisGlycolysis and Gluco و من أحياها

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Biochemistry of Carbohydrates

The figure represent the overall carbohydrate metabolic

reaction that start glucose which glycolysis to pyruvate

Using 2 ATP,2NADH and in the presense of O2 they will

enter citric acid cycle (aerobic oxidation )and convert to

CO2 +H2O ,2NAD+, 30-38 ATP by the oxidative

phosphorylation, And without O2 (anaerobic)

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(fermentation) they will convert to Lactate in ANIMALS

but in yeast, bacteria they will convert to 2CO2+2Ethanol

and only 2ATP.

Therefore, what we notes here that there is from 15to

19 increasing in ATP aerobic oxidation (30-38) VS

anaerobic oxidation (2).

Which is better for losing weight, aerobic or anaerobic

oxidation? Anaerobic, because we are going to oxidize

a lot of Glucose to produce enough of ATP.

Glycolysis• The Breakdown of Glucose

• Primary Energy Source of Cells

• Central Metabolic Pathway

• All Reactions Occur in Cytoplasm

• Two Phases

• Produces 2Pyruvates, 2 ATP, 2 NADH

• Regulation

Phase 1

ATP Investment

ATP ADP

ATP ADP

Phase 2

Energy Production

2ADP 2ATP

2ADP 2ATP

2 NAD+ 2NADH

This pathway is important because it is the central

pathway to energy production.

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Glucose is not found free in our muscle but its stored as

glycogen, once your body need glucose the glycogen will

Be degrade and glucose will be produced immediately

although fatty acid will be oxidized they will provide

more energy than glucose because they are not

dissolved easily in blood to be transported to your

muscles like glucose.

Every cell must do glycolysis because it regulates

metabolism, and without it metabolism will stop.

All reactions of glycolysis occur in cytoplasm but other

pathways of citric acid cycle take place in mitochondria.

Other metabolic pathways such as gluconeogenesis,

which has two places, one in mitochondria and the

other one in cytoplasm.

Glycolytic pathway could be divided into two phases. In

Phase 1 the reactions require ATP in order to Start

oxidizing, (in glycolysis there is only one oxidation

reaction and it is completed when CO2 and H2O in citric

acid cycle).

In phase 2, there is ATP production.

The net production of the two phases is two ATP

molecules

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Glycolysis• Glucose

• Stored in Polymers (Amylose/Amylopectin/Glycogen)

• poison

• Readily Released

• Travels Easily in Blood

• Made from Simple Precursors (Gluconeogenesis)

Glycolysis: the oxidation of glucose.

Phase 1

• Regulated Step of Glycolysis

• ΔG°’ = -16.7 kJ/mol

Glucose

Hexokinase

Glucose-6-Phosphate (G6P)

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First reaction .

Hexokinase:

Hexo= Work on substrate of six carbon atoms.

Kinase = phosphorylation.

Phosphorylation---> Glucose, fructose, galactose

Inhibited by G6P.

Low Km.

Phosphorylation is important because you are trapping

glucose in cell and preventing it from going back to blood

cycle.

Phosphate group will be transferred into the Carbon

number 6.

Glycolysis

Hexokinase

• Found in Virtually All Cells

• Hexokinase is Not Specific for Glucose

• Glucokinase - Higher Km

ATP

Glucose

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• Inhibited by G6P Product

Glucokinase is another Enzyme that is specific to glucose

only found in liver induce by insulin unlike Hexokinase.

Induction means that insulin will stimulate the synthesis

of Glucokinase and the synthesis of other enzymes is

one of the regulatory steps in metabolism and when you

synthesis more of this enzyme you are activating it.

(18:45)**

In the figure, we noticed very big enzyme and very tiny

substrate so enzyme is important, how? it will help

these small substrate to find each other and start

catalyzing and without Enzymes the reaction will not

take place.

Hexokinase

Substrates

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7 reaction reversible &3 reactions irreversible.

2nd

Enzymatic

reaction

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high (-) ^G, one direction ,irreversible.

Seven reactions out of ten of the glycolysis are

reversible.

Regulation of PFK1 is important so that ATP (substrate)

regulate the enzyme. How? At low concentration of

ATP, the enzyme is very active and at high ATP

concentration, the enzyme will be inhibited, why?

Because the purpose of glycolysis is to produce energy,

so if we have excess of energy in the form of ATP the

glycolysis will shut off.

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How does the same molecule at low concentration act

as activator, but at high concentration act as inhibitor?

Because of Different sites of binding. At high

concentration, it binds to regulatory site and shift it to

right (T state, low affinity to substrate).

When F6P convert to F1, 6BP the reaction must continue

to the end.

Transporting phosphate group into the Carbon number

1.

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F2, 6BP is the most Important regulator of carbohydrate

glycolysis but it is not an Intermediate in glycolytic

pathway .

Why is AMP positive (activator) regulator to PFK1? AMP

presents in low energy state but ATP presents in high-

energy state.

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Why is ΔG’° odd?

Because it is reversible, highly positive and in order to

make this reaction go forward the cell have to make ^G

negative, how? Next slide…

Two half each one have 3

carbon

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In order to make this reaction happen in forward pathway, the cell has to maintain ^G negative, by making less logarithmic term more negative than 23.9, how? By increasing the concentration of the reactants and decreasing the concentration of products. As much as negative quantities we have, as much as negative ^G.

It does that by pushing and pulling. Pushing of reactants to be in high concentration, and pulling of products to be in law concentration. (the pushing and pulling mechanisms)

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Because glycolysis must continue, the cell is being very active in producing F-1,6BP and it will accumulate at high (+) ^G and this high [F1,6BP] is used by the cell as an activator for the last step of glycolysis which is pyruvate kinase (that will convert phosphoenolpyruvate to pyruvate), (phosphoenolpyruvate coming from GA1P,GA3P,dihydroxyacetone phosphate(DHAP),2PG)so When this enzyme is activated by this feed forward activation, the product will be absorbed and taken out and thus will decrease the products and increase the reactants, thus we will have the ^G negative, and the Reaction will go forward.

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Triose Phosphate Isomerase Not regulatory but

important which is controlled by diffusion of substrate.

Perfect enzyme the enzymes that regulated substrate diffusion & work Very fast.

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All dehydrogenizes (enzyme) require coenzyme NAD or FAD, and Pi.

Conversion of oxidation of aldehyde to Ester(carboxylic group stifled to phosphate), usually in order to bond

Very toxic to cell so the

enzyme help in not forming

this

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phosphate group to substrate the energy in ATP will help but here we do not have ATP to help binding the phosphate. So how the phosphorus is easily bonded GA3P to form 1,3BPGA? From the oxidation (the released energy).

*Conversion of two electrons to change NAD ــ> NADH+.

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Here will produce two ATP because we have two molecules of 1,3BPGA.

What makes this phosphate move two ADP to Form ATP?

The presence of two negative charges repels them each other and transfer them. This is called the production of ATP in absence of oxidative phosphorylation (substrate level phosphorylation).

Three means of making ATP:

1. Substrate level phosphorylation - high-energy molecule adds phosphate to ADP.

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2. Oxidative phosphorylation - oxidative energy (electron movement) used in mitochondria to generate ATP

3. Photophosphorylation - light energy captured in chloroplasts of plants to make ATP

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