Metabolism Chapter 25: Metabolism and Nutrition

2/20/2011

1

Copyright 2009, John Wiley & Sons, Inc.

Chapter 25: Metabolism and Nutrition


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


Role of ATP in linking anabolic and catabolic reactions


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


3 Mechanisms of ATP generation1. Substrate-level phosphorylation Transferring high-energy phosphate group

from an intermediate directly to ADP2. Oxidative phosphorylation Remove electrons and pass them through

electron transport chain to oxygen3. Photophosphorylation Only in chlorophyll-containing plant cells


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

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Glucose catabolism / cellular respiration

1. Glycolysis Anaerobic respiration – does not require

oxygen2. Formation of acetyl coenzyme A3. Krebs cycle reactions4. Electron transport chain reactions Aerobic respiration – requires oxygen


Overview of cellular respiration

1NADH + 2 H+

GLYCOLYSIS2

2

2 Pyruvic acid

1 Glucose

ATP1

NADH + 2 H+GLYCOLYSIS

+ 2 H+NADH

CO2FORMATIONOF ACETYLCOENZYME A

2

2

2

2

2 Acetylcoenzyme A

2 Pyruvic acid

1 Glucose

ATP

2

1NADH + 2 H+

GLYCOLYSIS

+ 2 H+NADH


KREBSCYCLE

+ 6 H+

CO2

FADH2

NADH

2

4

6

2

2

2

2

2

2 Acetylcoenzyme A

2 Pyruvic acid

1 Glucose

ATP

ATP

2

3

1NADH + 2 H+

GLYCOLYSIS

+ 2 H+NADH


KREBSCYCLE

+ 6 H+

CO2

FADH2

NADH

2

4

6

2

ELECTRONTRANSPORTCHAIN

e–

e–

e–

32 or 34

O26

6

2

2

2

2

H2O

Electrons

2 Acetylcoenzyme A

2 Pyruvic acid

1 Glucose

ATP

ATP ATP

2

3

4


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


Cellular respiration begins with glycolysis


The 10 reactions of glycolysis

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3

ADP

O

Glucose (1 molecule)

CH2OH

OH

OH

OH4 1

3 2

5

6

ATP

H H

H

HHO

1

H

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

OH2CP

ATP

H

HO

H

H

HH

H

H

H

HO

1

2

H

H

Phosphofructokinase

ADP

O


CH2OH

OH

OH

OH4 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

OH2CP

ATP

ATP

OH

H

HO

H

H

HH

H H

H

H

HO

H

HO

1

2

3

H

H

Phosphofructokinase

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O

Fructose 1, 6-bisphosphate

O

OH

H

OH2C

ADP

PP

P

OH2CP

ATP

ATP

OH

H

HO

H

H

HH

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

H

H

Phosphofructokinase

Dihydroxyacetonephosphate

CH2OH

CH2OC O

Glyceraldehyde3-phosphate

HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

OH

H

HO

H

H

HH

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

H

H

+ 2H+NADH

HCOHC

CH2O

OO 1, 3-Bisphosphoglyceric acid

(2 molecules)

2

P

P

Phosphofructokinase


CH2OH

CH2OC O


HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

OH

H

HO

H

H

HH

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

HCOHC

CH2O

O

COOH

O

2

2 ADP

HCOHCH2O

1, 3-Bisphosphoglyceric acid(2 molecules)

2

3-Phosphoglyceric acid(2 molecules)

P

P

P

Phosphofructokinase


CH2OH

CH2OC O


HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

ATP

OH

H

HO

H

H

HH

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7H

H

2 NAD+ + 2 P

+ 2H+NADH

HCOHC

CH2O

O

COOH

O

2

2 ADP

HCOHCH2O


2


COOH

CH2OHHCO 2-Phosphoglyceric acid

(2 molecules)P

P

P

P

Phosphofructokinase


CH2OH

CH2OC O


HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

ATP

OH

H

HO

H

H

HH

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

HCOHC

CH2O

O

COOH

O

2

2 ADP

HCOHCH2O


2


COOH


(2 molecules)

COOH

CH2

C O Phosphoenolpyruvic acid(2 molecules)

P

P

P

P

P

Phosphofructokinase


CH2OH

CH2OC O


HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

ATP

OH

H

HO

H

H

HH

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

HCOHC

CH2O

O

COOH

O

2

2 ADP

P

HCOHCH2O


2


COOH


(2 molecules)

Pyruvic acid(2 molecules)

COOH

CH2

2

2 ADP

C O Phosphoenolpyruvic acid(2 molecules)

COOH

CH3

C O

P

P

P

P

P

Phosphofructokinase


CH2OH

CH2OC O


HCOHCH2O

OHC

ADP

O


CH2OH

OH

OH

OH4 1

3 2

5

6

Glucose 6-phosphate

O

OH

OH

OH

CH2OH


O

OH

H

OH2C 6

5

4 3

2

1

CH2O


O

OH

H

OH2C

ADP

PP

P

P

P

OH2CP

ATP

ATP

ATP

ATP

OH

H

HO

H

H

HH

H

H

H

H

H

H

HO

HO

H

HO

OH

1

2

3

4

5

6

7

8

9

10

H

H


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)


Fate of pyruvic acid


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


The Krebs Cycle


The Eight reactions of the Krebs cycle

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1

CCH2

COOHO

Oxaloacetic acid

COOHCitric acid

H2C COOHCOOHHOC

H2C COOH

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O

To electrontransport chain

H2O

CO2

NAD+

KREBSCYCLE

NADH

CoA

CoA

1

CCH2

COOHO

Oxaloacetic acid

COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


H2O

CO2

NAD+

KREBSCYCLE

NADH

CoA

CoA

2

1


CO2

+ H+

CCH2

COOHO

Oxaloacetic acid

COOH

Alpha-ketoglutaric acid

H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

NAD+

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

CoA

CoA

2

3

O

1


CO2

+ H+NADH

CO2

+ H+

CCH2

COOHO

Oxaloacetic acid

COOH

Succinyl CoA

H2C COOHCH2

C S CoA Alpha-ketoglutaric acid

H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

NAD+

NAD+

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

O

CoA

O

CoA

2

3

4

1


CO2

+ H+NADH

CO2

+ H+

CCH2

COOHO

Oxaloacetic acid

COOH

H2C COOHH2C COOHSuccinic acid

Succinyl CoA

H2C COOHCH2


H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

NAD+

NAD+

GDP

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


ADP

H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

ATP

GTP

O

CoA

CoA

O

CoA

2

3

4

5

1


CO2

+ H+NADH

CO2

+ H+

To electrontransportchain

CCH2

COOHO

Oxaloacetic acid

COOH


Succinyl CoA

H2C COOHCH2


H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

HCCH

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


ADP

FADH2

COOH

COOH

H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

O

1


CO2

+ H+NADH

CO2

+ H+


CCH2

COOHO

Oxaloacetic acid

COOH

HCOHCH2

COOH

COOH


Malic acid

Succinyl CoA

H2C COOHCH2


H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

HCCH

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


ADP

FADH2

COOH

COOH

H2O

H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

7

O

1


CO2

+ H+NADH

CO2

+ H+


CCH2

COOHO

Oxaloacetic acid

COOH

+ H+NADH

HCOHCH2

COOH

COOH


Malic acid

Succinyl CoA

H2C COOHCH2


H2C COOHHCH

C COOH

Isocitric acid

H2C COOH

HOC COOHHC COOH

H

Citric acid

H2C COOHCOOHHOC

H2C COOH

Fumaric acid

NAD+

NAD+

GDP

FAD

NAD+

HCCH

+ H+Pyruv ic

acidAcetyl

coenzyme A

CCH3

OCH3

CCOOH

O


ADP

FADH2

COOH

COOH

H2O

H2O

CO2

NAD+

KREBSCYCLE

NADH

NADH

ATP

GTP

CoA

CoA

O

CoA

2

3

4

5

6

7

8

O


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


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 fromNADH + H+

H+

Low H+ concentration inmatrix of mitochondrion

Innermitochondrialmembrane

Matrix

High H+ concentrationbetween inner andouter mitochondrialmembranes

Outer membraneInner membrane

H+

channel

Electrontransport

chain(includes

proton pumps)

1 Energy fromNADH + H+

H+

H+

Low H+ concentration inmatrix of mitochondrion


Matrix



H+

channel

Electrontransport

chain(includes

proton pumps)

1

2

Energy fromNADH + H+

H+

H+

ADP +

ATP synthaseLow H+ concentration inmatrix of mitochondrion


Matrix



H+

channel

Electrontransport

chain(includes

proton pumps)

P

ATP

1

2

3


The actions of the three proton pumps and ATP synthase in the inner membrane of mitochondria

Space between outerand inner mitochondrialmembranes

Innermito-chondrialmembrane

Mitochondrialmatrix

H+ channel

NADH dehydrogenasecomplex: FMN andfive Fe-S centers

NAD

e–

H++ + + + + + +

– – – – – – –

Q

NADH+ H+

1



Mitochondrialmatrix

H+ channel


Cytochrome b-c1complex: cyt b, cyt c1, and an Fe-S center

NAD

e–

e–

e–

H++ + + + + + +

– – – – – – –

Q

Cyt c

NADH+ H+H+

1 2



Mitochondrialmatrix

H+ channel


Cytochrome b-c1complex: cyt b, cyt c1, and an Fe-S center

Cytochrome oxidasecomplex: cyt a, cyt a3,and two Cu

NAD1 1/2 O2

e–

e–

e–

e–

e–

H+ H+H+

+ + + + + + +

– – – – – – –

H2O

Q

Cyt c

NADH+ H+H+

3

ADP +

ATP synthase

P

ATP1 2 3

3


Summary of cellular respiration

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5


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


Glycogenesis and glycogenolysis


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


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


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


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

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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


Pathways of lipid metabolism


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


Various points at which amino acids enter the Krebs cycle for oxidation


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


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

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7


Key molecules at metabolic crossroads2. 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


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


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


Principal metabolic pathways during the absorptive state

AMINO ACIDS GLUCOSE TRIGLYCERIDES(in chylomicrons)

Blood

GLUCOSE

GASTROINTESTINALTRACT

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

1


Blood

GLUCOSE


HEPATOCYTES IN LIVER

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Fatty acids

Triglycerides

Glyceraldehyde3-phosphate Glycogen

Glucose

+ H2O +CO2 ATP

1

2


Blood

GLUCOSE



+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fatty acids

Triglycerides


Glucose

+ H2O +CO2 ATP

1

2

3


Blood

GLUCOSE


GLUCOSE


SKELETALMUSCLE

Storage

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Fattyacids

Triglycerides


Glucose

Fatty acids

Triglycerides


Glucose

GlycogenGlycogen

+ H2O +CO2 ATP

1

2

3

4

4


Blood

GLUCOSE


GLUCOSE


SKELETALMUSCLE

Storage

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fattyacids

Triglycerides


Glucose

Fatty acids

Triglycerides


Glucose

GlycogenGlycogen

+ H2O +CO2 ATP

1

2

3

4 5

4


Blood

GLUCOSE


GLUCOSE


SKELETALMUSCLE

Storage

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fattyacids

Triglycerides


Glucose

Keto acids

Fatty acids

Triglycerides


Glucose

GlycogenGlycogen

+ H2O +CO2 ATP

1

2

3

4 5

6

4


Blood

GLUCOSE


GLUCOSE


SKELETALMUSCLE

Storage

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fattyacids

Triglycerides


Glucose

Keto acids

Fatty acidsProteins

Triglycerides


Glucose

GlycogenGlycogen

+ H2O +CO2 ATP

1

2

3

4 5

67

4


Blood

GLUCOSE


GLUCOSE


SKELETALMUSCLE

Storage

+ H2O +CO2

MOST TISSUES

Oxidation

ATP

Triglycerides

ADIPOSE TISSUE

VLDLs

Triglycerides

Fattyacids

Triglycerides


Glucose

Keto acids

Fatty acidsProteins

Triglycerides


Glucose

GlycogenGlycogen

ProteinsProteins

+ H2O +CO2 ATP

1

2

3

4 5

67

8

4


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

2/20/2011

8


Principal metabolic pathways during the postabsorptive state

1

Liver glycogen

Glucose

LIVER

Blood

HEARTADIPOSE TISSUESKELETAL MUSCLE TISSUE

OTHER TISSUES

1

Liver glycogen

Glucose

LIVER

Glycerol

Blood

HEART

Fatty acidsGlycerol

TriglyceridesADIPOSE TISSUE

SKELETAL MUSCLE TISSUE

OTHER TISSUES

2

Fatty acids

1

Liver glycogen

Glucose

LIVER

Lactic acid

Glycerol

Blood

HEART

Fatty acidsGlycerol



OTHER TISSUES3

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Lactic acid

Glycerol

Blood

HEART

Muscle proteins

Fatty acidsGlycerol


Fasting orstarvation


OTHER TISSUES

ProteinsAmino 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 acidsGlycerol




OTHER TISSUES

Fatty acids

ProteinsAmino acids

Amino acidsFatty 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 acidsGlycerol




OTHER TISSUES

Fatty acids

ProteinsAmino acids


Lactic acidATP

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 acidsGlycerol




OTHER TISSUES

Fatty acids

ProteinsAmino acids


Lactic acidATP

ATPATP

ATP

ATP

4

5

5

67

4

3

5

4

2

Fatty acids

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Fatty acids

Lactic acid

Ketone bodies

Glycerol

Blood

NERVOUSTISSUE Ketone

bodiesGlucose

Starvation

HEART

Fatty acids

Muscle proteins

Fatty acidsGlycerol




Ketone bodies

OTHER TISSUES

Fatty acids

ProteinsAmino acids


Ketone bodies

Lactic acidATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP ATP

4

5

8

5

6

88

7

4

3

5

4

2

8

1

Liver glycogen

Keto acids

Glucose

Amino acids

LIVER

Fatty acids

Lactic acid

Ketone bodies

Glycerol

Blood

NERVOUSTISSUE Ketone

bodiesGlucose

Starvation

HEART

Fatty acids

Muscle proteins

Fatty acidsGlycerol




Ketone bodies

OTHER TISSUES

Fatty acids

ProteinsAmino acids

Glucose6-phosphate

Pyruvic acid

Lacticacid

Muscle glycogen

(aerobic) (anaerobic)


Ketone bodies

Lactic acidATP

O2

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP

ATP ATP

+ O2–

4

5

8

5

6

88

7

4

3

9

5

4

2

8


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


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


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.


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

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9


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


Negative feedback mechanisms that conserve heat and increase increase production


Nutrition Nutrients are chemical substances in food that body

cells use for growth, maintenance, and repair 6 main types

1. Water – needed in largest amount2. Carbohydrates3. Lipids4. Proteins5. Minerals6. Vitamins

Essential nutrients must be obtained from the diet


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


MyPyramid


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

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10


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


End of Chapter 25

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Metabolism Chapter 25: Metabolism and Nutrition

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