Chem 45 Biochemistry: Stoker chapter 24 Carbohydrate Metabolism

Chapter 24

Carbohydrate

Metabolism

Chapter 24

Table of Contents

Copyright © Cengage Learning. All rights reserved 2

24.1 Digestion and Absorption of Carbohydrates

24.2 Hormonal Control of Carbohydrate Metabolism

24.3 Glycogen Synthesis and Degradation

24.4 Gluconeogenesis

24.5 The Pentose Phosphate Pathway

24.6 Glycolysis

24.7 Terminology for Glucose Metabolic Pathways

24.8 The Citric Acid Cycle

24.9 The Electron Transport Chain

24.10 Oxidative Phosphorylation

24.11 ATP Production for the Complete Oxidation of Glucose

24.12 Importance of ATP

24.13 Non-ETC Oxygen-Consuming Reactions

24.14 B-Vitamins and Carbohydrate Metabolism

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Digestion and Absorption of Carbohydrates

Section 24.1



Section 24.1


• Carbohydrate digestion: Begins in the mouth

– Salivary enzyme “α-amylase” catalyzes the hydrolysis of α-

glycosidic linkages of starch and glycogen to produce smaller

polysaccharides and disaccharide – maltose

– Only a small amount of carbohydrate digestion occurs in the

mouth because food is swallowed so quickly into the stomach

• In stomach very little carbohydrate is digested:

– No carbohydrate digestion enzymes present in stomach

– Salivary amylase gets inactivated because of stomach acidity


Section 24.1


• The primary site for the carbohydrate digestion is within

the small intestine

– Pancreatic α-amylase breaks down polysaccharide chains into

disaccharide – maltose

• The final step in carbohydrate digestion occurs on the

outer membranes of intestinal mucosal cells

– Maltase – hydrolyses maltose to glucose

– Sucrase – hydrolyses sucrose to glucose and fructose

– Lactase – hydrolyses lactose to glucose and galactose

• Glucose, galactose, and fructose are absorbed into the

bloodstream through the intestinal wall.

• Galactose and Fructose are converted to products of

glucose metabolism in the liver.


Section 24.1


• Following absorption the monosaccharides are carried by the

portal vein to the liver where galactose and fructose are

enzymatically converted to glucose intermediates that enter

into the glycolysis pathway

• The glucose may then pass into the general circulatory

system to be transported to the tissues or converted to

glycogen reserve in the liver.

• The glucose in the tissues may be

a) oxidized to CO2 and H2O (ATP)

b) converted to fat

c) converted to muscle glycogen

Metabolism

Section 23.1

• Blood-sugar level:

– the proper functions of the body are dependent on precise control of the glucose

concentration in the blood.

– the normal fasting level of glucose in the blood is 70-90 mg/100 ml.

• Abnormal conditions:

• A. hypoglycemia

– condition resulting from a lower than the normal blood-sugar level (below 70 mg/100 ml)

– extreme hypoglycemia, usually due to the presence of excessive amounts of insulin, is

characterized by general weakness, trembling, drowsiness, headache, profuse perspiration,

rapid heart beat, lowered blood pressure and possible loss of consciousness.

– Loss of consciousness is most likely due to the lack of glucose in the brain tissue, which is

dependent upon this sugar for its energy.

• B. hyperglycemia

– higher than the normal level (above 120 mg/100 mL); when the pancreas does not secrete

enough insulin

– may temporarily exist as a result of eating a meal rich in carbohydrates.

– extreme hyperglycemia, the renal threshold (160-170 mg/100 mL) is reached and excess

glucose is excreted in the urine


Section 24.9

Hormonal Control of Carbohydrate Metabolism


• Besides enzyme inhibition, carbohydrate metabolism may be

regulated by hormones

• Three major hormones control carbohydrate metabolism:

– Insulin ; Glucagon ; Epinephrine

• Insulin • 51 amino acid polypeptide secreted by the pancreas

• Promotes utilization of glucose by cells

• The release of insulin is triggered by high blood-glucose levels

• Its function is to lower blood glucose levels by enhancing the formation of

glycogen from glucose (glycogen synthesis)

• The mechanism for insulin action involves insulin binding to proteins

receptors on the outer surfaces of cells which facilitates entry of the glucose

into the cells

Section 24.9

Hormonal Control of Carbohydrate Metabolism


Glucagon

• 29 amino acid peptide hormone produced in the pancreas

• Released when blood glucose levels are low

• Principal function is to increase blood-glucose concentration by

speeding up the conversion of glycogen to glucose (glycogenolysis)

in the liver

• Glucagon elicits the opposite effects of insulin

Epinephrine (also called adrenaline)

• Released by the adrenal glands in response to anger, fear, or excitement

• Function is similar to glucagon, i.e., stimulates glycogenolysis

• Primary target of epinephrine is muscle cells

• Promotes energy generation for quick action

Metabolism

Section 23.1

• There are six major

metabolic pathways

of glucose:

1) Glycogenesis

2) Glycogenolysis

3) Gluconeogenesis

4) Hexose monophosphate

shunt

5) Glycolysis

6) Citric Acid Cycle


Section 24.5

Glycogen Synthesis and Degradation


Glycogenesis and Glycogenolysis

• Involved in the regulation of blood glucose concentration

• When the dietary intake of glucose exceeds immediate needs,

humans and other animals can convert the excess to glycogen,

which is stored in either the liver or muscle tissue.

• Glycogenesis is the pathway that converts glucose into glycogen.

• When there’s need for additional blood glucose, glycogen is

hydrolyzed and released into the bloodstream.

• Glycogenolysis is the pathway that hydrolyzes glycogen to

glucose.

Section 24.6

Gluconeogenesis


• Metabolic pathway by which glucose is synthesized from non-

carbohydrate sources:

– The process is not exact opposite of glycolysis

• Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours

from fasting or in even less time from heavy work or strenuous physical

activity

• Without gluconeogenesis, the brain, which is dependent on glucose as a

fuel would have problems functioning if food intake were restricted for even

one day

• Gluconeogenesis helps to maintain normal blood-glucose levels in times of

inadequate dietary carbohydrate intake

• About 90% of gluconeogenesis takes place in the liver

• Non-carbohydrate starting materials for gluconeogenesis:

– Pyruvate

– Lactate (from muscles and from red blood cells)

– Glycerol (from triacylglycerol hydrolysis)

– Certain amino acids (from dietary protein hydrolysis or from muscle protein

during starvation)

Section 24.8

The Pentose Phosphate Pathway


Hexose monophosphate shunt

• Initial reactant of the pathway is glucose-6-

phosphate

• Also termed phosphogluconate pathway,

because 6–phosphogluconate is one of the

intermediates

• A third name is pentose phosphate pathway,

because ribose-5-phosphate is one of its

products

• The main purposes of the HMP shunt are the

following:

– to produce ribose-5-P for nucleotide

synthesis

– to produce NADPH from NADP+ for fatty

acid and steroid biosynthesis and for

maintaining reduced glutathione (GSH)

inside erythrocytes

– to interconvert pentoses and hexoses

•

Section 24.2

Glycolysis


• A series of reactions in the

cytoplasm which converts

glucose (C6) to two molecules of

pyruvate (a C3 carboxylate), and

ATP and NADH are produced.

• Also called Embden-Meyerhof

pathway, after the scientist who

elucidated the pathway

• an anaerobic process; each

step takes place without O2; one

of its advantages, the body can

obtain energy from glycolysis

quickly, without waiting for a

supply of O2 to be carried to the

cells.

• occurs in cells lacking

mitochondria, e.g., erythrocytes

and in certain skeletal muscle

cells during intense muscle

activity

Section 24.2

Glycolysis


• Step 1: Formation of glucose-6-phosphate:

– Endothermic reaction catalyzed by

hexokinase

– Energy needed is derived from ATP

hydrolysis

• Step 2: Formation of Fructose-6-phosphate:

– Enzyme: Phosphoglucoisomerase

• Step 3: Formation of Fructose 1,6-bisphosphate:

– Enzyme: phosphofructokinase

• Step 4: Formation of Triose Phosphates:

– C6 species is split into two C3 species

– Enzyme : Aldolase

• Step 5: Isomerization of Triose Phosphates

– DHAP is isomerized to glyceraldehyde 3-

phosphate

– Enzyme: Triosephosphate isomerase

• Step 6: Formation of 1,3-bisphosphoglycerate

– Glyceraldehyde 3-phosphate is oxidized and

phosphorylated

– Enzyme: Glyceraldehyde-3-phosphate

dehydrogenase

Section 24.2

Glycolysis


• Step 7: Formation of 3-bisphosphoglycerate

– It is an ATP producing step

– Enzyme: phosphoglycerokinase

• Step 8: Formation of 2-phosphoglycerate

– Isomerization of 3-phosphoglycerate to

2-phosphoglycerate

– Enzyme: phosphoglyceromutase

• Step 9: Formation of Phosphoenolpyruvate:

– Enzyme: Enolase

• Step 10: Formation of Pyruvate:

– High energy phosphate is transferred

from phosphoenolpyruvate to ADP

molecule to produce ATP and pyruvate

– Enzyme: Pyruvate kinase

• At this point of carbohydrate metabolism

there are at least 2 directions that the

product pyruvate may take.

• The direction depends primarily upon the

availability of oxygen in the cell:

Section 24.2

Glycolysis


Section 24.2

Glycolysis


• If there is adequate oxygen, an aerobic

pathway is followed and pyruvate

enters the Krebs cycle.

• If there is insufficient oxygen available,

the anaerobic pathway is continued

and pyruvate undergoes a series of

reactions to produce lactic acid.

• Lactic acid then is the end-product of

glycolysis, and if there were not some

mechanism for its removal, it would

accumulate in the muscle cells & cause

muscle “crumps”.

• Bacteria also use lactate fermentation

in the production of yogurt and cheese

• Reactions 1 9 are identical for

glycolysis and alocoholic fermentation

• for pyruvic acid, the crossroads

compound, its metabolic fate depends

upon the conditions (aerobic or

anaerobic) and upon the organism

under consideration.

Section 24.2

Glycolysis


Section 24.6

Gluconeogenesis


The Cori cycle. Lactate, formed from

glucose under anaerobic conditions in

muscle cells (glycolysis), is transferred

to the liver, where it is reconverted to

glucose (gluconeogenesis), which is

then transferred back to the muscle

cells.

Section 24.7

Terminology For Glucose Metabolic Pathways


Relationships Among Four Common Metabolic Pathways That

Involve Glucose

Section 24.2

Glycolysis


ATP Production and Consumption

• There is a net gain of two ATP molecules in glycolysis for every

glucose molecule processed

• Overall equation for glycolysis

G l u c o s e + 2 N A D +

2 P y r u v a t e + 2 N A D H + 2 H +

+ 2 H 2 O

2 A D P + 2 P i 2 A T P

Section 23.7

The Citric Acid Cycle


• Citric acid cycle: A series of

biochemical reactions in which the

acetyl portion of acetyl CoA is

oxidized to carbon dioxide and ATP

and the reduced coenzymes FADH2

and NADH are produced

• Takes place in the mitochondria

• Also known as tricarboxylic acid

cycle (TCA) or Krebs cycle:

– Named after Hans Krebs who

elucidated this pathway

• Two important types of reactions:

– Reduction of NAD+ and FAD to

produce NADH and FADH2

– Decarboxylation of citric acid to

produce carbon dioxide

– The citric acid cycle also

produces 2 ATP by substrate

level phosphorylation from GTP

Section 23.7



• Step 1: Formation of Citrate

• Step 2: Formation of

Isocitrate

• Step 3: Oxidation of Isocitrate

and Formation of CO2:

involves oxidation–reduction

as well as decarboxylation

• Step 4: Oxidation of Alpha-

Ketoglutarate and Formation

of CO2

• Step 5: Thioester bond

cleavage in Succinyl CoA

and Phosphorylation of GDP

to form GTP

• Step 6: Oxidation of

Succinate

• Step 7: Hydration of

Fumarate

• Step 8: Oxidation of L-Malate

to regenerate Oxaloacetate

Section 23.7



• Important features of the cycle:

• The reactions of the cycle takes place in the mitochondrial matrix, except the succinate

dehydrogenase reaction that involves FAD. The enzyme that catalyzes this reaction is an

integral part of the inner mitochondrial membrane.

• The “fuel “ for the cycle is acetyl CoA, obtained from the breakdown of carbohydrates, fats,

and proteins.

• Four of the cycle reactions involve oxidation and reduction. The oxidizing agent is either

NAD+ (three times) or FAD (once). The operation of the cycle depends on the availability of

these oxidizing agents.

• In redox reactions, NAD+ is the oxidizing agent when a carbon-oxygen double bond is

formed; FAD is the oxidizing agent when a carbon-carbon double bond is formed.

• The three NADH and the one FADH2 that are formed during the cycle carry electrons and

H+ to the electron transport chain through which ATP is synthesized.

• Two carbon atoms enter the cycle as acetyl unit of the acetyl CoA, and two carbon atoms

leave the cycle as two molecules of CO2. The carbon atoms that enter and leave are not

the same ones. The carbon atoms that leave during one turn of the cycle are carbon atoms

that entered during the previous turn of the cycle.

• Four B vitamins are necessary for the proper functioning of the cycle: riboflavin (in both

FAD and α-ketoglutarate dehydrogenase complex), nicotinamide (in NAD+), pantothenic

acid (in CoASH), and thiamin (in α-ketoglutarate dehydrogenase complex)

• One high-energy GTP molecule is produced by substrate level phosphorylation.

Section 23.7


Copyright © Cengage Learning. All rights reserved

26

Regulation of the Citric Acid Cycle

• The rate at which the citric acid cycle operates is controlled by ATP

and NADH levels

• When ATP supply is high, ATP inhibits citrate synthase (Step 1 of

Citric acid cycle)

• When ATP levels are low, ADP activates citrate synthase

• Similarly ADP and NADH control isocitrate dehydrogenase:

– NADH acts as an inhibitor

– ADP as an activator.

Section 23.8

The Electron Transport Chain


• The electron transport chain (ETC) facilitates the passage of

electrons trapped in FADH2 and NADH during citric cycle

• ETC is a series of biochemical reactions in which intermediate

carriers (protein and non-protein) aid the transfer of electrons and

hydrogen ions from NADH and FADH2

• The ultimate receiver of electrons is molecular oxygen

• The electron transport (respiratory chain) gets its name from the fact

that electrons are transported to oxygen absorbed via respiration

• ETC is the sequence of reactions whereby the reduced forms of the

coenzymes are reoxidized, ultimately by O2

Section 23.8



• The enzymes and electron carriers needed for the ETC

are located along inner mitochondrial membrane

• They are organized into four distinct protein complexes

and two mobile carriers

• The four protein complexes tightly bound to membrane:

• Complex 1: NADH-coenzyme Q reductase

• Complex II: Succinate-coenzyme Q reductase

• Complex III: Coenzyme Q - cytochrome C reductase

• Complex IV: Cytochrome C oxidase

• Two mobile electron carriers are:

– Coenzyme Q and cytochrome c.

Section 23.8



Complex I: NADH-

Coenzyme Q Reductase

• Facilitates transfer of

electrons from NADH

to coenzyme Q

Complex II: Succinate-

Coenzyme Q Reductase

• Succinate is converted

to fumarate by this

complex

• In the process it

generates FADH2

• CoQ is the final

recipient of the

electrons from FADH2

Section 23.8



Complex III: Coenzyme Q –

Cytochrome c Reductase

• Several iron-sulfur proteins

and cytochromes are electron

carriers in this complex

• Cytochrome is a heme iron

protein in which reversible

oxidation of an iron atom

occurs Complex IV: Coenzyme Q –

Cytochrome c Reductase

• The electrons flow from cyt c to

cyt a to cyt a3

• In the final stage of electron

transfer, the electrons from cyt

a3, and hydrogen ion (H+)

combine with oxygen (O2) to

form water

• O2 + 4H+ + 4e- 2 H2O

Section 23.8



• Summary of the flow of electrons through four

complexes of the electron transport chain.

Section 23.9

Oxidative Phosphorylation


• Oxidative phosphorylation – process by which ATP

is synthesized from ADP and Pi using the energy

released in the electron transport chain by coupled

reactions

• Coupled Reactions -- are pairs of biochemical

reactions that occur concurrently in which energy

released by one reaction is used in the other

reaction

– example: oxidative phosphorylation and the

oxidation reactions of the electron transport

chain are coupled systems

Section 23.9



• The coupling of ATP synthesis with the reactions of the ETC is related to the

movement of protons (H+ ions) across the inner mitochondrial membrane

• Complexes I, III and IV of ETC chain also serve as “proton pumps” to transfer

protons from the matrix side of the inner membrane to the intermembrane space

• For every two electrons passed through ETC, four protons cross the inner

mitochondrial membrane through complex I, four through complex III and two more

though complex IV

• This proton flow causes a buildup of H+ in the intermembrane space

• The high [H+] in the intermembrane space becomes the basis for ATP synthesis

Section 23.9



• The resulting concentration

difference (high in

intermembrane space than in

matrix) constitutes an

electrochemical (proton)

gradient which is always

associated with potential energy

• The gradient build-up would

spontaneously push the H+ ions

through membrane-bound ATP

synthase

• Proton flow is not through the

membrane itself since it is not

permeable to H+ ions

• The proton flow through the

ATP synthetases powers the

synthesis of ATP

• ATP synthetases are the

coupling factors in the ETC/OP

coupled reactions

Section 23.10

ATP Production for the Common Metabolic Pathway


• Formation of ATP accompanies

the flow of protons from the

intermembrane space back into

the mitochondrial matrix.

• The proton flow results from an

electrochemical gradient across

the inner mitochondrial

membrane

• For each mole of NADH

oxidized in the ETC, 2.5 moles

of ATP are formed.

• For each mole of FADH2

Oxidized in the ETC, only 1.5

moles of ATP are formed.

• For each mole of GTP

hydrolyzed one mole of ATP

are formed.

• Ten molecules of ATP are

produced for each acetyl CoA

catabolized in the TCA

Section 23.9



Summary of the Common Metabolic Pathway

Section 24.4

ATP Production for the Complete Oxidation of Glucose


Section 24.4



• Cytosolic NADH produced

during Step 6 of Glycolysis

cannot directly participate in

the electron transport chain

because mitochondria are

impermeable to NADH and

NAD+

• Glycerol 3-phosphate-

dihydroxyacetone phosphate

transport system shuttles

electrons from NADH, but

not NADH itself, across the

membrane:

– Dihydroxyacetone

phosphate and glycerol

phosphate freely cross

the mitochondrial

membrane

– The interconversion

shuttles the electrons

from NADH to FADH2

Section 24.4



• A total of 30 ATP molecules are produced in muscle and

nerve cells:

– 26 from oxidative phosphorylation / electron transport

chain coupled reactions

– 2 from oxidation of glucose to pyruvate

– 2 from conversion of GTP to ATP

• Aerobic oxidation of glucose is 15 times more efficient in

the ATP production as compared to anaerobic lactate

and ethanol processes

• In other cells such as heart and liver cells a more

complex shuttle system is used and 32 molecules are

produced instead of 30 per glucose molecule

Section 23.11

The Importance of ATP


• The cycling of ATP and ADP in metabolic processes is

the principal medium for energy exchange in biochemical

processes

Section 23.12

Non-ETC Oxygen-Consuming Reactions


• >90% of inhaled oxygen via respiration is consumed

during oxidative phosphorylation.

• Remaining O2 are converted to several highly reactive

oxygen species (ROS) with in the body.

• Examples of ROS:

– Hydrogen peroxide (H2O2)

– Superoxide ion (O2-) and

– Hydroxyl radical (OH)

– Superoxide ion and hydroxyl radicals have unpaired electron

and are extremely reactive

• ROS can also be formed due to external influences such

as polluted air, cigarette smoke, and radiation exposure

Section 23.12



• Reactive oxygen species (ROS) are both beneficial as

well a problematic within the body

• Beneficial Example: White blood cells produce a

significant amount of superoxide free radicals via the

following reaction to destroy the invading bacteria and

viruses.

– 2O2 + NADPH 2O2- + NADP+ + H+

Section 23.12



• > 95% of the ROS formed are quickly converted to non

toxic species :

• About 5% of ROS escape destruction by superoxide

dismutase and catalase enzymes.

2O2- + 2H+ H2O2 + O2

Superoxidedismutase

H2O + O2Catalase2H2O2

Section 23.12



• Antioxidant molecules present in the body help trap ROS

species

• Antioxidants present in the body:

• Vitamin K

• Vitamin C

• Glutathione (GSH)

• Beta-carotene

• Plant products such as flavonoids are also good

antioxidants – Have shown promise in the management

of many disorders associated with ROS production

Section 23.13

B Vitamins and the Common Metabolic Pathway


• Structurally modified B-vitamins function as coenzymes

in the metabolic pathways

• Four B Vitamins participate in various reactions:

– Niacin – NAD+ and NADH

– Riboflavin – as FAD, FADH2 and FMN

– Thiamin – as TPP

– Pantothenic acid - as CoA

• With out these B-vitamins body would be unable to

utilize carbohydrates, proteins and fats as energy

sources.

Section 24.10

B-Vitamins and Carbohydrate Metabolism


Chem 45 Biochemistry: Stoker chapter 24 Carbohydrate Metabolism

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