chapter 25: metabolism and nutrition

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Copyright 2009, John Wiley & Sons, Inc. Chapter 25: Metabolism and Nutrition

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Copyright 2009, John Wiley & Sons, Inc.

Chapter 25: Metabolism and

Nutrition

Copyright 2009, John Wiley & Sons, Inc.

Metabolism

Metabolism – refers to all chemical reaction occurring in body

Catabolism – break down complex molecules Exergonic – produce more energy than they consume

Anabolism – combine simple molecules into complex ones Endergonic – consume more energy than they produce

Adenosine triphosphate (ATP)

“energy currency”

ADP + P + energy ↔ ATP

Copyright 2009, John Wiley & Sons, Inc.

Role of ATP in linking anabolic and

catabolic reactions

Copyright 2009, John Wiley & Sons, Inc.

Energy transfer

Oxidation-reduction or redox reactions

Oxidation – removal of electrons

Decrease in potential energy

Dehydrogenation – removal of hydrogens

Liberated hydrogen transferred by coenzymes

Nicotinamide adenine dinucleotide (NAD)

Flavin adenine dinucleotide (FAD)

Glucose is oxidized

Reduction – addition of electrons

Increase in potential energy

Copyright 2009, John Wiley & Sons, Inc.

3 Mechanisms of ATP generation

1. Substrate-level phosphorylation

Transferring high-energy phosphate group

from an intermediate directly to ADP

2. Oxidative phosphorylation

Remove electrons and pass them through

electron transport chain to oxygen

3. Photophosphorylation

Only in chlorophyll-containing plant cells

Copyright 2009, John Wiley & Sons, Inc.

Carbohydrate metabolism

Fate of glucose depends on needs of body cells

ATP production or synthesis of amino acids, glycogen, or triglycerides

GluT transporters bring glucose into the cell via facilitate diffusion

Insulin causes insertion of more of these transporters, increasing rate of entry into cells

Glucose trapped in cells after being phosphorylated

Copyright 2009, John Wiley & Sons, Inc.

Glucose catabolism / cellular respiration

1. Glycolysis

Anaerobic respiration – does not require

oxygen

2. Formation of acetyl coenzyme A

3. Krebs cycle reactions

4. Electron transport chain reactions

Aerobic respiration – requires oxygen

Copyright 2009, John Wiley & Sons, Inc.

Overview of cellular respiration

1

NADH + 2 H+

GLYCOLYSIS 2

2

2 Pyruvic acid

1 Glucose

ATP 1

NADH + 2 H+

GLYCOLYSIS

+ 2 H+ NADH

CO2 FORMATION

OF ACETYL

COENZYME A

2

2

2

2

2 Acetyl

coenzyme A

2 Pyruvic acid

1 Glucose

ATP

2

1

NADH + 2 H+

GLYCOLYSIS

+ 2 H+ NADH

CO2 FORMATION

OF ACETYL

COENZYME A

KREBS

CYCLE + 6 H+

CO2

FADH2

NADH

2

4

6

2

2

2

2

2

2 Acetyl

coenzyme A

2 Pyruvic acid

1 Glucose

ATP

ATP

2

3

1

NADH + 2 H+

GLYCOLYSIS

+ 2 H+ NADH

CO2 FORMATION

OF ACETYL

COENZYME A

KREBS

CYCLE + 6 H+

CO2

FADH2

NADH

2

4

6

2

ELECTRON

TRANSPORT

CHAIN

e–

e–

e–

32 or 34

O2 6

6

2

2

2

2

H2O

Electrons

2 Acetyl

coenzyme A

2 Pyruvic acid

1 Glucose

ATP

ATP ATP

2

3

4

Copyright 2009, John Wiley & Sons, Inc.

Glycolysis

1. Glycolysis

Splits 6-carbon glucose into 2 3-carbon molecules of pyruvic acid

Consumes 2 ATP but generates 4

10 reactions

Fate of pyruvic acid depends on oxygen availability

If oxygen is scarce (anaerobic), reduced to lactic acid

Hepatocytes can convert it back to pyruvic acid

If oxygen is plentiful (aerobic), converted to acetyl coenzyme A

Copyright 2009, John Wiley & Sons, Inc.

Cellular respiration begins with glycolysis

Copyright 2009, John Wiley & Sons, Inc.

The 10 reactions of glycolysis

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

ATP

H H

H

H HO

1

H

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

OH2C P

ATP

H

HO

H

H

H H

H

H

H

HO

1

2

H

H

Phosphofructokinase

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

ADP

P

OH2C P

ATP

ATP

OH

H

HO

H

H

H H

H H

H

H

HO

H

HO

1

2

3

H

H

Phosphofructokinase

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

OH2C P

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

H

H

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

H

H

+ 2H+ NADH

HCOH

C

CH2O

O

O 1, 3-Bisphosphoglyceric acid

(2 molecules)

2

P

P

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

H

H

2 NAD+ + 2 P

+ 2H+ NADH

HCOH

C

CH2O

O

COOH

O

2

2 ADP

HCOH

CH2O

1, 3-Bisphosphoglyceric acid

(2 molecules)

2

3-Phosphoglyceric acid

(2 molecules)

P

P

P

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7 H

H

2 NAD+ + 2 P

+ 2H+ NADH

HCOH

C

CH2O

O

COOH

O

2

2 ADP

HCOH

CH2O

1, 3-Bisphosphoglyceric acid

(2 molecules)

2

3-Phosphoglyceric acid

(2 molecules)

COOH

CH2OH

HCO 2-Phosphoglyceric acid

(2 molecules)

P

P

P

P

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7

8

H

H

2 NAD+ + 2 P

+ 2H+ NADH

HCOH

C

CH2O

O

COOH

O

2

2 ADP

HCOH

CH2O

1, 3-Bisphosphoglyceric acid

(2 molecules)

2

3-Phosphoglyceric acid

(2 molecules)

COOH

CH2OH

HCO 2-Phosphoglyceric acid

(2 molecules)

COOH

CH2

C O Phosphoenolpyruvic acid

(2 molecules) P

P

P

P

P

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7

8

9

H

H

2 NAD+ + 2 P

+ 2H+ NADH

2 NAD+ + 2

HCOH

C

CH2O

O

COOH

O

2

2 ADP

P

HCOH

CH2O

1, 3-Bisphosphoglyceric acid

(2 molecules)

2

3-Phosphoglyceric acid

(2 molecules)

COOH

CH2OH

HCO 2-Phosphoglyceric acid

(2 molecules)

Pyruvic acid

(2 molecules)

COOH

CH2

2

2 ADP

C O Phosphoenolpyruvic acid

(2 molecules)

COOH

CH 3

C O

P

P

P

P

P

Phosphofructokinase

Dihydroxyacetone

phosphate

CH2OH

CH2O

C O

Glyceraldehyde

3-phosphate

HCOH

CH2O

O H

C

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH

4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH

Fructose 6-phosphate

O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

P P

P

P

P

OH2C P

ATP

ATP

ATP

ATP

OH

H

HO

H

H

H H

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7

8

9

10

H

H

Copyright 2009, John Wiley & Sons, Inc.

Formation of Acetyl coenzyme A

2. Formation of Acetyl coenzyme A

Each pyruvic acid converted to 2-carbon acetyl

group

Remove one molecule of CO2 as a waste product

Each pyruvic acid also loses 2 hydrogen atoms

NAD+ reduced to NADH + H+

Acetyl group attached to coenzyme A to form

acetyl coenzyme A (acetyl CoA)

Copyright 2009, John Wiley & Sons, Inc.

Fate of pyruvic acid

Copyright 2009, John Wiley & Sons, Inc.

The Krebs cycle

3. The Krebs cycle

Also known as citric acid cycle

Occurs in matrix of mitochondria

Series of redox reactions

2 decarboxylation reactions release CO2

Reduced coenzymes (NADH and FADH2) are

the most important outcome

One molecule of ATP generated by substrate-

level phosphorylation

Copyright 2009, John Wiley & Sons, Inc.

The Krebs Cycle

Copyright 2009, John Wiley & Sons, Inc.

The Eight reactions of the Krebs cycle

1

C

CH2

COOH

O

Oxaloacetic acid

COOH Citric acid

H2C COOH

COOH HOC

H2C COOH

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

H2O

CO2

NAD+

KREBS

CYCLE

NADH

CoA

CoA

1

C

CH2

COOH

O

Oxaloacetic acid

COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

H2O

CO2

NAD+

KREBS

CYCLE

NADH

CoA

CoA

2

1

To electron

transport chain

CO2

+ H+

C

CH2

COOH

O

Oxaloacetic acid

COOH

Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

NAD+

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

CoA

CoA

2

3

O

1

To electron

transport chain

CO2

+ H+ NADH

CO2

+ H+

C

CH2

COOH

O

Oxaloacetic acid

COOH

Succinyl CoA

H2C COOH

CH2

C S CoA Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

NAD+

NAD+

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

O

CoA

O

CoA

2

3

4

1

To electron

transport chain

CO2

+ H+ NADH

CO2

+ H+

C

CH2

COOH

O

Oxaloacetic acid

COOH

H2C COOH

H2C COOH

Succinic acid

Succinyl CoA

H2C COOH

CH2

C S CoA Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

NAD+

NAD+

GDP

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

ADP

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

ATP

GTP

O

CoA

CoA

O

CoA

2

3

4

5

1

To electron

transport chain

CO2

+ H+ NADH

CO2

+ H+

To electron

transport

chain

C

CH2

COOH

O

Oxaloacetic acid

COOH

H2C COOH

H2C COOH

Succinic acid

Succinyl CoA

H2C COOH

CH2

C S CoA Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

HC

CH

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

ADP

FADH2

COOH

COOH

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

O

1

To electron

transport chain

CO2

+ H+ NADH

CO2

+ H+

To electron

transport

chain

C

CH2

COOH

O

Oxaloacetic acid

COOH

HCOH

CH2

COOH

COOH

H2C COOH

H2C COOH

Succinic acid

Malic acid

Succinyl CoA

H2C COOH

CH2

C S CoA Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

HC

CH

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

ADP

FADH2

COOH

COOH

H2O

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

7

O

1

To electron

transport chain

CO2

+ H+ NADH

CO2

+ H+

To electron

transport

chain

C

CH2

COOH

O

Oxaloacetic acid

COOH

+ H+ NADH

HCOH

CH2

COOH

COOH

H2C COOH

H2C COOH

Succinic acid

Malic acid

Succinyl CoA

H2C COOH

CH2

C S CoA Alpha-ketoglutaric acid

H2C COOH

HCH

C COOH

Isocitric acid

H2C COOH

HOC COOH

HC COOH

H

Citric acid

H2C COOH

COOH HOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

NAD+

HC

CH

+ H+

Pyruvic

acid

Acetyl

coenzyme A

C

CH3

O

CH3

C

COOH

O

To electron

transport chain

ADP

FADH2

COOH

COOH

H2O

H2O

CO2

NAD+

KREBS

CYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

7

8

O

Copyright 2009, John Wiley & Sons, Inc.

Electron transport chain

4. Electron transport chain

Series of electron carriers in inner mitochondrial

membrane reduced and oxidized

As electrons pass through chain, exergonic

reactions release energy used to form ATP

Chemiosmosis

Final electron acceptor is oxygen to form water

Copyright 2009, John Wiley & Sons, Inc.

Chemiosmosis

Carriers act as proton pumps to expel H+ from

mitochondrial matrix

Creates H+ electrochemical gradient – concentration

gradient and electrical gradient

Gradient has potential energy – proton motive force

As H+ flows back into matrix through membrane,

generates ATP using ATP synthase

Energy from

NADH + H+

H+

Low H+ concentration in

matrix of mitochondrion

Inner

mitochondrial

membrane

Matrix

High H+ concentration

between inner and

outer mitochondrial

membranes

Outer membrane

Inner membrane

H+

channel

Electron

transport

chain

(includes

proton pumps)

1 Energy from

NADH + H+

H+ H+

Low H+ concentration in

matrix of mitochondrion

Inner

mitochondrial

membrane

Matrix

High H+ concentration

between inner and

outer mitochondrial

membranes

Outer membrane

Inner membrane

H+

channel

Electron

transport

chain

(includes

proton pumps)

1

2

Energy from

NADH + H+

H+ H+

ADP +

ATP synthase Low H+ concentration in

matrix of mitochondrion

Inner

mitochondrial

membrane

Matrix

High H+ concentration

between inner and

outer mitochondrial

membranes

Outer membrane

Inner membrane

H+

channel

Electron

transport

chain

(includes

proton pumps)

P

ATP

1

2

3

Copyright 2009, John Wiley & Sons, Inc.

The actions of the three proton pumps and ATP synthase

in the inner membrane of mitochondria

Space between outer and inner mitochondrial membranes

Inner mito- chondrial membrane

Mitochondrial matrix

H+ channel

NADH dehydrogenase complex: FMN and five Fe-S centers

NAD

e–

H+ + + + + + + +

– – – – – – –

Q

NADH + H+

1

Space between outer and inner mitochondrial membranes

Inner mito- chondrial membrane

Mitochondrial matrix

H+ channel

NADH dehydrogenase complex: FMN and five Fe-S centers

Cytochrome b-c1 complex: cyt b, cyt c1, and an Fe-S center

NAD

e–

e–

e–

H+ + + + + + + +

– – – – – – –

Q

Cyt c

NADH + H+ H+

1 2

Space between outer and inner mitochondrial membranes

Inner mito- chondrial membrane

Mitochondrial matrix

H+ channel

NADH dehydrogenase complex: FMN and five Fe-S centers

Cytochrome b-c1 complex: cyt b, cyt c1, and an Fe-S center

Cytochrome oxidase complex: cyt a, cyt a3,and two Cu

NAD

1 1/2 O2

e–

e–

e–

e–

e–

H+ H+ H+

+ + + + + + +

– – – – – – –

H2O

Q

Cyt c

NADH + H+ H+

3

ADP +

ATP synthase

P

ATP

1 2 3

3

Copyright 2009, John Wiley & Sons, Inc.

Summary of cellular respiration

Copyright 2009, John Wiley & Sons, Inc.

Glucose anabolism

Glucose storage: glycogenesis

Polysaccharide that is the only stored carbohydrate in

humans

Insulin stimulates hepatocytes and skeletal muscle cells

to synthesize glycogen

Glucose release: glycogenolysis

Glycogen stored in hepatocytes broken down into

glucose and release into blood

Copyright 2009, John Wiley & Sons, Inc.

Glycogenesis and glycogenolysis

Copyright 2009, John Wiley & Sons, Inc.

Formation of glucose from proteins and

fats: gluconeogenesis

Glycerol part of

triglycerides, lactic acid,

and certain amino acids

can be converted by the

liver into glucose

Glucose formed from

noncarbohydrate

sources

Stimulated by cortisol

and glucagon

Copyright 2009, John Wiley & Sons, Inc.

Lipid metabolism

Transport by lipoproteins

Most lipids nonpolar and

hydrophobic

Made more water-soluble

by combining them with

proteins to form lipoproteins

Proteins in outer shell called

apoproteins (apo)

Each has specific functions

All essentially are transport

vehicles

Copyright 2009, John Wiley & Sons, Inc.

Apoproteins Apoproteins categorized and named according to density (ratio of

lipids to proteins)

Chylomicrons

Form in small intestine mucosal epithelial cells

Transport dietary lipids to adipose tissue

Very low-density lipoproteins (VLDLs)

Form in hepatocytes

Transport endogenous lipids to adipocytes

Low-density lipoproteins (LDLs) – “bad” cholesterol

Carry 75% of total cholesterol in blood

Deliver to body cells for repair and synthesis

Can deposit cholesterol in fatty plaques

High-density lipoproteins (HDLs) – “good” cholesterol

Remove excess cholesterol from body cells and blood

Deliver to liver for elimination

Copyright 2009, John Wiley & Sons, Inc.

Lipid Metabolism

2 sources of cholesterol in the body Present in foods

Synthesized by hepatocytes

As total blood cholesterol increases, risk of coronary artery disease begins to rise Treated with exercise, diet, and drugs

Lipids can be oxidized to provide ATP Stored in adipose tissue if not needed for ATP

Major function of adipose tissue to remove triglycerides from chylomicrons and VLDLs and store it until needed 98% of all body energy reserves

Copyright 2009, John Wiley & Sons, Inc.

Lipid Metabolism

Lipid catabolism: lipolysis

Triglycerides split into glycerol and fatty acids

Must be done for muscle, liver, and adipose tissue to oxidize fatty acids

Enhanced by epinephrine and norepinephrine

Lipid anabolism: lipogenesis

Liver cells and adipose cells synthesize lipids from glucose or amino acids

Occurs when more calories are consumed than needed for ATP production

Copyright 2009, John Wiley & Sons, Inc.

Pathways of lipid metabolism

Copyright 2009, John Wiley & Sons, Inc.

Protein metabolism

Amino acids are either oxidized to produce ATP or used to synthesize new proteins

Excess dietary amino acids are not excreted but converted into glucose (gluconeogenesis) or triglycerides (lipogenesis)

Protein catabolism

Proteins from worn out cells broken down into amino acids

Before entering Krebs cycle amino group must be removed – deamination

Produces ammonia, liver cells convert to urea, excreted in urine

Copyright 2009, John Wiley & Sons, Inc.

Various points at which amino acids enter

the Krebs cycle for oxidation

Copyright 2009, John Wiley & Sons, Inc.

Protein anabolism

Carried out in ribosomes of almost every cell in the body

10 essential amino acids in the human

Must be present in the diet because they cannot be

synthesized

Complete protein – contains sufficient amounts of all essential

amino acids – beef, fish, poultry, eggs

Incomplete protein – does not – leafy green vegetables,

legumes, grains

10 other nonessential amino acids can be synthesized by

body cells using transamination

Copyright 2009, John Wiley & Sons, Inc.

Key molecules at metabolic crossroads

3 molecules play pivotal roles in metabolism

Stand at metabolic crossroads – reactions

that occur or not depend on nutritional or

activity status of individual

1. Glucose 6-phosphate

Made shortly after glucose enters body cell

4 fates – synthesis of glycogen, release of

glucose into blood stream, synthesis of nucleic

acids, glycolysis

Copyright 2009, John Wiley & Sons, Inc.

Key molecules at metabolic crossroads

2. Pyruvic acid

If there is enough oxygen, aerobic cellular respiration

occurs

If there is not enough oxygen, anaerobic reactions can

produce lactic acid, produce alanine or gluconeogenesis

3. Acetyl Coenzyme A

When ATP is low and oxygen plentiful, most pyruvic acid

goes to ATP production via Acetyl CoA

Acetyl CoA os the entry into the Krebs cycle

Can also be used for synthesis of certain lipids

Copyright 2009, John Wiley & Sons, Inc.

Metabolic adaptations

During the absorptive state ingested nutrients are entering the blood stream

Glucose readily available for ATP production

During postabsorptive state absorption of nutrients from GI tract complete

Energy needs must be met by fuels in the body

Nervous system and red blood cells depend on glucose so maintaining steady blood glucose critical

Effects of insulin dominate

Copyright 2009, John Wiley & Sons, Inc.

Metabolism during absorptive state

Soon after a meal nutrients enter blood

Glucose, amino acids, and triglycerides in chylomicrons

2 metabolic hallmarks

Oxidation of glucose for ATP production in all body cells

Storage of excess fuel molecules in hepatocytes,

adipocytes, and skeletal muscle cells

Pancreatic beta cells release insulin

Promotes entry of glucose and amino acids into cells

Copyright 2009, John Wiley & Sons, Inc.

Principal metabolic pathways during the

absorptive state

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

1

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

HEPATOCYTES IN LIVER

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Fatty acids

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

+ H2O + CO2 ATP

1

2

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

HEPATOCYTES IN LIVER

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty acids

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

+ H2O + CO2 ATP

1

2

3

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

GLUCOSE

HEPATOCYTES IN LIVER

SKELETAL

MUSCLE

Storage

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Fatty

acids

Triglycerides

Glyceraldehyde

3-phosphate

Glucose

Fatty acids

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

Glycogen Glycogen

+ H2O + CO2 ATP

1

2

3

4

4

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

GLUCOSE

HEPATOCYTES IN LIVER

SKELETAL

MUSCLE

Storage

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty

acids

Triglycerides

Glyceraldehyde

3-phosphate

Glucose

Fatty acids

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

Glycogen Glycogen

+ H2O + CO2 ATP

1

2

3

4 5

4

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

GLUCOSE

HEPATOCYTES IN LIVER

SKELETAL

MUSCLE

Storage

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty

acids

Triglycerides

Glyceraldehyde

3-phosphate

Glucose

Keto acids

Fatty acids

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

Glycogen Glycogen

+ H2O + CO2 ATP

1

2

3

4 5

6

4

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

GLUCOSE

HEPATOCYTES IN LIVER

SKELETAL

MUSCLE

Storage

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty

acids

Triglycerides

Glyceraldehyde

3-phosphate

Glucose

Keto acids

Fatty acids Proteins

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

Glycogen Glycogen

+ H2O + CO2 ATP

1

2

3

4 5

6

7

4

AMINO ACIDS GLUCOSE TRIGLYCERIDES

(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINAL TRACT

GLUCOSE

HEPATOCYTES IN LIVER

SKELETAL

MUSCLE

Storage

+ H2O + CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty

acids

Triglycerides

Glyceraldehyde

3-phosphate

Glucose

Keto acids

Fatty acids Proteins

Triglycerides

Glyceraldehyde

3-phosphate Glycogen

Glucose

Glycogen Glycogen

Proteins Proteins

+ H2O + CO2 ATP

1

2

3

4 5

6

7

8

4

Copyright 2009, John Wiley & Sons, Inc.

Metabolism during postabsorptive state

About 4 hours after the last meal absorption in small intestine nearly complete

Blood glucose levels start to fall

Main metabolic challenge to maintain normal blood glucose levels

Glucose production

Breakdown of liver glycogen, lipolysis, gluconeogenesis using lactic acid and/or amino acids

Glucose conservation

Oxidation of fatty acids, lactic acid, amino acids, ketone bodies and breakdown of muscle glycogen

Copyright 2009, John Wiley & Sons, Inc.

Principal metabolic pathways during the

postabsorptive state

1

Liver glycogen

Glucose

LIVER

Blood

HEART ADIPOSE TISSUE SKELETAL MUSCLE TISSUE

OTHER TISSUES

1

Liver glycogen

Glucose

LIVER

Glycerol

Blood

HEART

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

SKELETAL MUSCLE TISSUE

OTHER TISSUES

2

Fatty acids

1

Liver glycogen

Glucose

LIVER

Lactic acid

Glycerol

Blood

HEART

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

SKELETAL MUSCLE TISSUE

OTHER TISSUES

3

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Lactic acid

Glycerol

Blood

HEART

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

OTHER TISSUES

Proteins Amino acids

Amino acids

4

4

3

4

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Lactic acid

Glycerol

Blood

HEART

Fatty acids

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

OTHER TISSUES

Fatty acids

Proteins Amino acids

Amino acids Fatty acids

ATP

ATP

ATP

4

5

5

4

3

5

4

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Lactic acid

Glycerol

Blood

HEART

Fatty acids

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

OTHER TISSUES

Fatty acids

Proteins Amino acids

Amino acids Fatty acids

Lactic acid

ATP

ATP

ATP

ATP

4

5

5

6

4

3

5

4

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Lactic acid

Glycerol

Blood

HEART

Fatty acids

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

OTHER TISSUES

Fatty acids

Proteins Amino acids

Amino acids Fatty acids

Lactic acid

ATP

ATP ATP

ATP

ATP

4

5

5

6 7

4

3

5

4

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Fatty acids

Lactic acid

Ketone bodies

Glycerol

Blood

NERVOUS

TISSUE Ketone

bodies

Glucose

Starvation

HEART

Fatty acids

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

Ketone bodies

OTHER TISSUES

Fatty acids

Proteins Amino acids

Amino acids Fatty acids

Ketone bodies

Lactic acid

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP ATP

4

5

8

5

6

8 8

7

4

3

5

4

2

8

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Fatty acids

Lactic acid

Ketone bodies

Glycerol

Blood

NERVOUS

TISSUE Ketone

bodies

Glucose

Starvation

HEART

Fatty acids

Muscle proteins

Fatty acids Glycerol

Triglycerides ADIPOSE TISSUE

Fasting or

starvation

SKELETAL MUSCLE TISSUE

Ketone bodies

OTHER TISSUES

Fatty acids

Proteins Amino acids

Glucose

6-phosphate

Pyruvic acid

Lactic

acid

Muscle glycogen

(aerobic) (anaerobic)

Amino acids Fatty acids

Ketone bodies

Lactic acid

ATP

O2

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP ATP

+ O2 –

4

5

8

5

6

8 8

7

4

3

9

5

4

2

8

Copyright 2009, John Wiley & Sons, Inc.

Hormones and autonomic nervous system

regulate metabolism during postabsorptive

state

As blood glucose decline, insulin secretion falls

Glucagon – increases release of glucose into blood via

gluconeogenesis and glycogenolysis

Sympathetic nerve endings of ANS release

norepinephrine and adrenal medulla releases

epinephrine and norepinephrine

Stimulate lipolysis, glycogen breakdown

Copyright 2009, John Wiley & Sons, Inc.

Heat and energy balance

Heat – form of energy that can be measured as

temperature and can be expressed in calories

calorie (cal) – amount of heat required to raise 1 gram of

water 1°C

Kilocalorie (kcal) or Calorie (Cal) is 1000 calories

Metabolic rate – overall rate at which metabolic

reactions use energy

Some energy used to make ATP, some lost as heat

Basal metabolic rate (BMR) – measurement with body in

quiet, resting, fasting condition

Copyright 2009, John Wiley & Sons, Inc.

Body temperature homeostasis

Despite wide fluctuations in environmental

temperatures, homeostatic mechanisms maintain

normal range for internal body temperature

Core temperature (37°C or 98.6°F) versus shell

temperature (1-6°C lower)

Heat produced by exercise, some hormones,

sympathetic nervous system, fever, ingestion of

food, younger age, etc.

Copyright 2009, John Wiley & Sons, Inc.

Heat and engery balance

Heat can be lost through

Conduction to solid materials in contact with body

Convection – transfer of heat by movement of a gas or liquid

Radiation – transfer of heat in form of infrared rays

Evaporation exhaled air and skin surface (insensible water loss)

Hypothalamic thermostat in preoptic area

Heat-losing center and heat-promoting center

Copyright 2009, John Wiley & Sons, Inc.

Thermoregulation

If core temperature declines

Skin blood vessels constrict

Release of thyroid hormones, epinephrine and

norepinephrine increases cellular metabolism

Shivering

If core body temperature too high

Dilation of skin blood vessels

Decrease metabolic rate

Stimulate sweat glands

Copyright 2009, John Wiley & Sons, Inc.

Negative feedback mechanisms that

conserve heat and increase increase

production

Copyright 2009, John Wiley & Sons, Inc.

Nutrition

Nutrients are chemical substances in food that body

cells use for growth, maintenance, and repair

6 main types

1. Water – needed in largest amount

2. Carbohydrates

3. Lipids

4. Proteins

5. Minerals

6. Vitamins

Essential nutrients must be obtained from the diet

Copyright 2009, John Wiley & Sons, Inc.

Guidelines for healthy eating

We do not know with certainty what levels and types of

carbohydrates, fat and protein are optimal

Different populations around the world eat radically

different diets adapted to their particular lifestyle

Basic guidelines

Eat a variety of foods

Maintain a healthy weight

Choose foods low in fat, saturated fat and cholesterol

Eat plenty of vegetables, fruits and grain products

Use sugars in moderation only

Copyright 2009, John Wiley & Sons, Inc.

MyPyramid

Copyright 2009, John Wiley & Sons, Inc.

Minerals

Inorganic elements that occur naturally in Earth’s

crust

Eat foods that contain enough calcium,

phosphorus, iron and iodine

Excess amounts of most minerals are excreted in

urine and feces

Major role of minerals to help regulate enzymatic

reactions

Copyright 2009, John Wiley & Sons, Inc.

Vitamins

Organic nutrients required in small amounts to maintain

growth and normal metabolism

Do not provide energy or serve as body’s building materials

Most are coenzymes

Most cannot be synthesized by the body

Vitamin K produced by bacteria in GI tract

Some can be assembled from provitamins

No single food contains all the required vitamins

2 groups

Fat-soluble – A, D, E, K

Water-soluble – several B vitamins and vitamin C

Copyright 2009, John Wiley & Sons, Inc.

End of Chapter 25

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