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CARBOHYDRATE METABOLISM Chapter 3 A. Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions. (thermodynamic basis for the operation of the metabolic pathways since most of these reaction sequences comprise endergonic as well as exergonic reactions.

A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

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Page 1: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

CARBOHYDRATE METABOLISM

Chapter 3A. Coupled reactionsThe additivity of free energy changes

allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions. (thermodynamic basis for the operation of the metabolic pathways since most of these reaction sequences comprise endergonic as well as exergonic reactions.

Page 2: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

BREAK-DOWN OF GLUCOSE TO GENERATE ENERGY

- Also known as Respiration. - Comprises of these different

processes depending on type of organism:

I. Anaerobic Respiration II. Aerobic Respiration

Page 3: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

ANAEROBIC RESPIRATION

Comprises of these stages: glycolysis: glucose 2 pyruvate + NADH fermentation: pyruvate lactic acid or ethanol cellular respiration:

Page 4: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

AEROBIC RESPIRATION

Comprises of these stages: Oxidative decarboxylation of pyruvate Citric Acid cycle Oxidative phosphorylation/ Electron Transport

Chain(ETC)

Page 5: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

STARCHY FOOD

α – AMYLASE ; MALTASES

Glycolysis in cytosol

Brief overview of catabolism of glucose to generate energy

Glucose converted to glu-6-PO4

Start of cycle

2[Pyruvate+ATP+NADH]

- Krebs Cycle

- E transport chain

Aerobic condition; in mitochondriaAnaerobic

condition

Lactic Acid fermentation in muscle.

Only in yeast/bacteria Anaerobic respiration or

Alcohol fermentation

Pyruvate enters as AcetylcoA

Glucose

Cycle : anaerobic

Page 6: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

GLYCOLYSIS

Show time..

Page 7: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

GLYCOLYSIS

1st stage of glucose metabolism → glycolysis An anaerobic process, yields 2 ATP

(additional energy source) Glucose will be metabolized via gycolysis;

pyruvate as the end product The pyruvate will be converted to lactic acid

(muscles → liver) Aerobic conditions: the main purpose is to

feed pyruvate into TCA cycle for further rise of ATP

Page 8: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-1, p.464

The breakdown of glucose to pyruvate as summarized:

Glucose (six C atoms) → 2 pyruvate (three C atoms)2 ATP + 4 ADP + 2 Pi → 2 ADP + 4 ATP (phosphorylation)Glucose + 2 ADP + 2 Pi → 2 Pyruvate + 2 ATP (Net reaction)

Page 9: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-2, p.465

Page 10: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Louis Pasteur- French biologist- did research on

fermentation which led to important discoveries in microbiology and chemistry

Page 11: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

HOW 6-CARBON GLUCOSE CONVERTED TO THE 3-CARBON GLYCERALDEHYDE-3-PHOSPHATE?

p.467

Step 1 Glucose is phosphorylated to give gluc-6-phosphatePreparation phase

Page 12: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-3, p.468

Page 13: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions
Page 14: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Table 17-1, p.469

Page 15: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-4, p.470

Page 16: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.470a

Step 2 Glucose-6-phosphate isomerize to give fructose-6-phosphate

Page 17: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.470b

Step 3 Fructose-6-phosphate is phosphorylated producing fructose-1,6-bisphosphate

Page 18: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-6, p.471

Page 19: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.471a

Step 4 Fructose-1,6-bisphosphate split into two 3-carbon fragments

Page 20: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.471b

Step 5 Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate

Page 21: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

HOW IS GLYCERALDEHYDE-6-PHOSPHATE CONVERTED TO PYRUVATE

p.472

Step 6

Payoff phase

Glyceraldehyde-6-phosphate is oxidized to 1,3-bisphosphoglycerate

Page 22: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-7, p.473

Page 23: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions
Page 24: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.474a

Page 25: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-8, p.475

Page 26: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.476

Step 7 Production of ATP by phosphorylation of ADP

Page 27: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.477a

Step 8 Phosphate group is transferred from C-3 to C-2

Page 28: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.477b

Step 9 Dehydration reaction of 2-phosphoglycerate to phosphoenolpyruvate

Page 29: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.478

Step 10 Phosphoenolpyruvate transfers its phosphate group to ADP → ATP and pyruvate

Page 30: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-10, p.479

Control points in glycolysis

Page 31: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

HOW IS PYRUVATE METABOLIZED ANAEROBICALLY?

p.479

Conversion of pyruvate to lactate in muscle

Page 32: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-11b, p.481

Page 33: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-11a, p.481

Pyruvate decarboxylase

Page 34: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 17-12, p.482

Page 35: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.482

Acetaldehyde + NADH → Ethanol + NAD+

Glucose + 2 ADP + 2 Pi + 2 H+ → 2 Ethanol + 2 ATP + 2 CO2 + 2 H2O

Page 36: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Carbohydrate metabolism

Chapter 3(cont.)

Page 37: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Gluconeogenesis

Conversion of pyruvate to glucose Biosynthesis and the degradation of many important biomolecules

follow different pathways There are three irreversible steps in glycolysis and the differences

bet. glycolysis and gluconeogenesis are found in these reactions Different pathway, reactions and enzyme

p.495

STEP 1

Page 38: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

is the biosynthesis of new glucose from non-CHO precursors. this glucose is as a fuel source by the brain, testes,

erythrocytes and kidney medulla

comprises of 9 steps and occurs in liver and kidney the process occurs when quantity of glycogen have been

depleted - Used to maintain blood glucose levels. Designed to make sure blood glucose levels are high enough

to meet the demands of brain and muscle (cannot do gluconeogenesis).

promotes by low blood glucose level and high ATP inhibits by low ATP occurs when [glu] is low or during periods of fasting/

starvation, or intense exercise pathway is highly endergonic *endergonic is energy consuming

Page 39: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

STEP 2

Page 40: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

The oxalocetate formed in the mitochondria have two fates:

- continue to form PEP- turned into malate by malate dehydrogenase and leave the mitochondria, have a reaction reverse by cytosolic malate dehydrogenase

Reason?

Page 41: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions
Page 42: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

as

Fig. 18-12, p.502

Controlling glucose metabolism• found in Cori cycle• shows the cycling of

glucose due to gycolysis in muscle and gluconeogenesis in liver

As energy store for next exercise

• This two metabolic pathways are not active simultaneously.

• when the cell needs ATP, glycolisys is more active

• When there is little need for ATP, gluconeogenesis is more active

Page 43: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Cori cycle requires the net hydrolysis of two ATP and two GTP.

OHATPHNADHPyruvate

PADPNADeglu i

222422

222cos

iPGDPADPNADeGlu

OHGTPATPHNADHPyruvate

6242cos

624422 2

iPGDPADP

OHGTPATP

422

422 2

Page 44: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 18-13, p.503

Page 45: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

The Citric Acid cycle

Cycle where 30 to 32 molecules of ATP can be produced from glucose in complete aerobic oxidation

Amphibolic – play roles in both catabolism and anabolism

The other name of citric acid cycle: Krebs cycle and tricarboxylic acid cycle (TCA)

Takes place in mitochondria

Page 46: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-2, p.513

Page 47: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions
Page 48: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-3b, p.514

Steps 3,4,6 and 8 – oxidation reactions

Page 49: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

5 enzymes make up the pyruvate dehydrogenase complex: pyruvate dehydrogenase (PDH) Dihydrolipoyl transacetylase Dihydrolipoyl dehydrogenase Pyruvate dehydrogenase kinase Pyruvate dehydrogenase phosphatase

Conversion of pyruvate to acetyl-CoA

Page 50: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.518

Step 1 Formation of citrate

Page 51: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Table 19-1, p.518

Step 2 Isomerization

Page 52: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-6, p.519

cis-Aconitate as an intermediate in the conversion of citrate to isocitrate

Page 53: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions
Page 54: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-7, p.521

Step 3

Formation of α-ketoglutarate and CO2 – first oxidation

Page 55: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.521

Step 4 Formation of succinyl-CoA and CO2 – 2nd oxidation

Page 56: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.522

Step 5 Formation of succinate

Page 57: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.523a

Step 6

Formation of fumarate – FAD-linked oxidation

Page 58: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.524a

Step 7 Formation of L-malate

Page 59: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

p.524b

Step 8 Regeneration of oxaloacetate – final oxidation step

Page 60: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-8, p.526

Krebs cycle produced:• 6 CO2

• 2 ATP• 6 NADH• 2 FADH2

Page 61: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Table 19-3, p.527

Page 62: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-10, p.530

Page 63: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-11, p.531

Page 64: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-12, p.533

Page 65: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Fig. 19-15, p.535

Page 66: A.Coupled reactions The additivity of free energy changes allows an endergonic reaction to be driven by an exergonic reaction under the proper conditions

Overall production from glycolysis, oxidative decarboxylation and TCA:

Oxidative decarboxylation

Glycolysis TCA cycle

- 2 ATP 2 ATP

2 NADH 2 NADH 6 NADH , 2 FADH2

2 CO2 2 Pyruvate 4 CO2

Electron transportation system