AMP Metabolism

8/2/2019 AMP Metabolism

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Food is..

.. Energy !

Rev iew concep ts

Catabolism: Metabolic reaction pathways that break down

food molecules and release biochemical energy.

Anabolism: Metabolic reactions that build larger biological

molecules from smaller pieces.

** Refer to sections 21.1 and 21.2


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Rev iew concep ts

Many metabolic reactions are redox

Reactions.

Coenzymes continuously cycle between

their oxidized and reduced forms.

Ex: NAD+ and NADH/H+

NADP+ and NADPH+/H+

FAD/FADH2

Rev iew concep ts

Exergonic and Endergonic reactions:

G = H TS

Spontaneous reactions release free energy,

which is available to do work. Exergonic reactions have

A negative G value. Endergonic reactions are a nonspontaneous

reaction or process that absorbs free energy and has a positive G.

** Refer to sections 21.1 and 21.2


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What is Acetyl-S-CoA ?

An important metabolic intermediate for breakdown of

all classes of food.

It is a thiol and can react with acids to form a thioester.

Aids in transfer of acetyl groups, (i.e acetyltransferase )

23.2 Glucose Metabolism: An Overview

When glucose enters a cell from the bloodstream, it isimmediately converted to glucose 6-phosphate.

Once this phosphate is formed, glucose is trapped within thecell because phosphorylated molecules cannot cross the cellmembrane.

Like the first step in many metabolic pathways, the formationof glucose-6-phosphate is highly exergonic and not reversiblein the glycolytic pathway, thereby committing the initialsubstrate to subsequent reactions.


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Glucose-6-phosphate can enter the pentose phosphate

pathway. This multistep pathway yields two products

of importance to our metabolism

One is a supply of the coenzyme NADPH, areducing agent that is essential for variousbiochemical reactions.

The other is ribose 5-phosphate, which isnecessary for the synthesis of nucleic acids (DNAand RNA).

When energy is needed, glucose 6-phosphateundergoes glycolysis to pyruvate and then to acetyl-S-coA,

which enters the citric acid cycle.

23.3 Glycolysis

Step 1. Conversion of Glucose Glucose-6-phosphate

Step 2. Glucose-6-phosphate Pyruvate (via several steps of

Glycolysis pathway)

Step 3. Pyruvate Acetyl-ScoA

Following: Glucose to Acetyl-ScoA (formation of the 6-phos

phate is highly exergonic, and irreversible)


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Glycolysis is a series of 10 enzyme-catalyzed reactionsthat break down glucose molecules.

The net result of glycolysis is the production of two

pyruvate molecules, two ATPs, and two NADH/H+s.

23.3 Glycolysis

Steps 1-5 of glycolysis break one glucose molecule down into

two D-glyceraldehyde 3-phosphate fragments.

An investment of 2 ATP molecules is required.

Steps 6-10 occur twice for each glucose that enters in at step 1.

Steps 6-10 produce: 2 pyruvates, 4 ATPs, 2 NADH/H+ per

glucose molecule

For complete reactions of glucose to pyruvate: Figure 23.3, page

720 of text

Glycolysis


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23.5 What happens to Pyruvate?

Structure of the multienzyme complex Pyruvate

Dehydrogenase, has a core

of 24 proteins.

A decarboxylation reaction

NAD+ reduces to NADH

S-CoA is dehydrogenated

Why do we call this an oxidation?

Anaerobic: In the absence of oxygen.

If electron transport slows because of insufficient oxygen,NADH concentration increases, NAD+ is in short supply,and glycolysis cannot continue.

An alternative way to reoxidize NADH is essential becauseglycolysis, the only available source of fresh ATP, mustcontinue. The reduction of pyruvate to lactate solves theproblem.

What happens to Pyruvate?


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21.7 What happens to Acetyl-SCoA?

21.7 Citric Acid Cycle (a.k.a TCA cycle, Krebs cycle)

-Takes place in mitochondria.

The acetyl group is converted

To CO2 (redox?)

-Cyclic pathway, why?

Explain the reaction from the Citric

Acid cycle and the enzyme class that will act as

catalysts.


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Net result of the Citric AcidCycle

The net result of the citric acid cycle is:

-Production of four reduced coenzymemolecules, 3 NADH and 1 FADH2

-Conversion of an acetyl group to twoCO2 molecules

-Production of one energy-richmolecule (GTP)

The eight steps of the citric acid cycle are shown ingreater detail on Section 21.8 of your text.

23.7 Regulation of Glucose Metabolism andEnergy Production

Normal blood glucose

concentration a few hours after a

meal ranges roughly from 65 to

110 mg/dL.

Hypoglycemia: Lower-than

normal blood glucose

concentration.

Hyperglycemia: Higher-than

normal blood glucose

concentration.


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Two hormones from the pancreas have the majorresponsibility for blood glucose regulation.

The first, insulin, is released when blood glucoseconcentration rises.

The second hormone, glucagon, is released when bloodglucose concentration drops.

23.8 Metabolism in Fasting and Starvation

The metabolic changes in the absence of food begin with a

gradual decline in blood glucose concentration

accompanied by an increased release of glucose from

glycogen.

All cells contain glycogen, but most is stored in liver cells

(about 90 g in a 70-kg man) and muscle cells (about 350 g

in a 70-kg man). Free glucose and glycogen represent less

than 1% of our energy reserves and are used up in 1520

hours of normal activity (3 hours in a marathon race).


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During the first few days of

starvation, protein is used

up at a rate as high as 75

g/day. Lipid catabolism is

mobilized, and acetyl-SCoA

molecules derived from

breakdown of lipids

accumulate.

Acetyl-SCoA begins to be

removed by a new series of

metabolic reactions that

transform it into ketonebodies.

As starvation continues, the brain and other tissues are able to

switch over to producing up to 50% of their ATP from

catabolizing ketone bodies instead of glucose. By the 40th day

of starvation, metabolism has stabilized at the use of about 25 g

of protein and 180 g of fat each day. So long as adequate water

is available, an average person can survive in this state for

several months; those with more fat can survive longer.


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23.9 Metabolism in Diabetes Mellitus

Diabetes mellitus: A chronic condition due to either

insufficient insulin or failure of insulin to activate crossing

of cell membranes, by glucose.

The symptoms by which diabetes is usually detected are

excessive thirst accompanied by frequent urination,

abnormally high glucose concentrations in urine and blood,

and wasting of the body despite a good diet. These

symptoms result when available glucose does not enter

cells where it is needed.

Type II diabetes is thought to result when cell membranereceptors fail to recognize insulin. Drugs that increase either

insulin or insulin receptor levels are an effective treatment

because more of the undamaged receptors are put to work.

Type I diabetes is classified as an autoimmune disease, a

condition in which the body misidentifies some part of itself as

an invader. Gradually, the immune system wrongly identifies

pancreatic beta cells as foreign matter, develops antibodies to

them, and destroys them. To treat Type I diabetes, the missing

insulin must be supplied by injection.


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Blood glucose concentration in

glucose tolerance test

for normal and diabetic individuals.

Metabolism ofTriAcylGlycerols

Pathways that break down

molecules (catabolism) are

shown in light brown, and

synthetic pathways

(anabolism) are shown in

blue. Connections to otherpathways or intermediates

of metabolism are shown in

green.


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25.5 Oxidation of Fatty Acids

Once a fatty acid enters the cytosol of a cell that needsenergy, three successive processes must occur.

1. Activation: The fatty acid must be activated by

conversion to fatty acyl-SCoA. Some energy from ATP

must initially be invested in converting the fatty acid to

fatty acyl-SCoA, a form that breaks down more easily.

2. Transport: The fatty acyl-SCoA must be transported into

the mitochondrial matrix where energy generation will occur.

Carnitine, a transmembrane protein found only in the

mitochondrial membrane, specifically moves fatty acyl-SCoA

across the membrane into the mitochondria.

3. Oxidation: The fatty acyl-SCoA must be oxidized by

enzymes in the mitochondrial matrix to produce acetyl-SCoA

plus the reduced coenzymes to be used in ATP generation.

The oxidation occurs by repeating the series of four reactions

which make up the -oxidation pathway.


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-Oxidation refers to the oxidation of the carbon atom to the

thioester linkage in two steps of the pathway.

STEP 1: The first oxidation: The oxidizing agent FADremoves hydrogen atoms from the carbon atoms and tothe C=O group in the fatty acyl-SCoA, forming a carbon

carbon double bond.

STEP 2: Hydration: A water molecule adds across the newly

created double bond to give an alcohol with the OH group on

the -carbon.

STEP 3: The second oxidation: NAD+ is the oxidizingagent for conversion of the group to a carbonyl group.

STEP 4: Cleavage to remove an acetyl group: An acetyl

group is split off and attached to a new coenzyme A molecule,

leaving behind an acyl-SCoA that is two carbon atoms shorter.


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The four steps of the -oxidation pathway:

25.6 Energy from Fatty Acid Oxidation

The total energy output from fatty acid catabolism is

measured by the total number of ATPs produced. Current

best estimates are that 2.5 ATPs result from each NADH

and 1.5 ATPs from each FADH2.

The -oxidation pathway produces 1 NADH and 1 FADH2or 4 ATPs per cycle.

Each acetyl-SCoA produces 3 NADH, 1 FADH2 and 1

ATP or 10 ATPs per acetyl-SCoA.

Lauric acid, CH3(CH2)10COOH, has 12 carbons.


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After initial activation (-2 ATP), five -oxidations (5x4 ATP =

+20 ATP) will change lauric acid into 6 acetyl-SCoA

molecules (6x10 ATP = + 60 ATP). The total energy yield is78 ATP per lauric acid.

1 mole (200g) lauric acid yields 78 moles ATP

1 mole (180g) glucose yields 30-32 moles ATP

Fats and oils yield 9 Calories per gram

Carbohydrates yield 4 Calories per gram

Each gram of glycogen can hold as much as 2 grams of water

so fats are almost 7 times more energy dense than

carbohydrates in the body.

C6H12O6+ 6 O2 6 CO2 + 6 H2O G = 686 kcal/mol

The oxidation of glucose, shown above, is an important reaction in the

body. This reaction is

1. endergonic, as represented by energy diagram (a).

2. exergonic, as represented by energy diagram (a).

3. endergonic, as represented by energy diagram (b).

4. exergonic, as represented by energy diagram (b).

Prac t ice qu es t ion s sec t ion


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In the pathways for the digestion of food and the production of

biochemical energy, the oxidation of Acetyl-SCoA occurs in

1. stage 1: digestion.

2. stage 2: Acetyl-SCoA

production.

3. stage 3: citric acid cycle.

4. stage 4: ATP production.

21.5 Write the products of Hydrolysis:


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What is the general class of enzyme that catalyzes this process ?

21.24 In which step is a coenzyme

needed? Identify the coenzyme. b)

In which step is carbon dioxide

evolved and a hydrogen ion added?

c) Which of the structures shown

can be described as a beta-keto

acid?


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Normal metabolism as well as unusual stresses

can produce reactive oxygen species capable of injuring cells.

In the induction stage of the Atkins diet ketosis is induced in

which blood glucose levels drop and blood ketone bodies

increase. Which of the compounds below are ketone bodies?

1. Acetone

2. Acetone and acetoacetate

3. 3-Hydroxybutyrate

4. All of the above

OH O

| ||

CH3CHCH2CO

3-Hydroxybutyrate

O O

|| ||

CH3CCH2CO

Acetoacetate

O

||

CH3CCH3Acetone


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When blood glucose levels rise following a meal, which of the

following events occurs first?

1. Blood levels pass through normal to below normal.

2. Glycolysis occurs to replenish the ATP supplies.

3. Glucose is absorbed by the cells.

4. Insulin levels rise.

The conjugat e base of the bile acid cholic acid and cholesterol areshown below. To what gener al class of compounds do th eybelong?

1. Eicosanoids

2. Fatty acids

3. Glycolipids

4. Steroids

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