copyright © 2006 by elsevier, inc. adenosine triphosphate (atp) - the central link between...

Copyright © 2006 by Elsevier, Inc.

Adenosine triphosphate (ATP) - the central link betweenenergy-producing and energy-using systems of the body

Figure 67-1; Guyton & Hall

Copyright © 2006 by Elsevier, Inc.Downloaded from: StudentConsult (on 1 March 2009 09:39 PM)

© 2005 Elsevier

ATP Structure


Phosphate Terminology

• Kinase– adds a phosphate

• phosphatase– removes a phosphate

• phosphorylase– splits a compound by adding a phosphate

(analagous to hydrolysis, but uses phosphate instead of water)


Glucose Transport Into Most Cells

• Down a concentration gradient by facilitated diffusion, – i.e. a carrier is required but energy is not

• There are many different carriers. The most important and commonly studied are– GLUT-1, does not require insulin

• note that most post-absorptive glucose uptake by cells does not require insulin

– GLUT-4, insulin dependent


Glycolysis

Glucose Fructose 1,6- diphosphate

(PP)

DihydroxyacetonePhosphate (DHAP)

Glyceraldehyde3-phosphate (GA 3-P)

2 ATP

2 Pyruvic Acid

4 ATP

2 NADH + 2H

Net Output:2 pyruvate2 NADH + H (4 H’s)2 ATP

4 ADP

2 NAD+

H3C - C - C

O O

OH

H3C - C - S - CoA

O

Transport into Mitochrondrion

NADH + H

CO2

HS - CoA

Go from 3-Cpyruvate to ...

... a 2-C Acetyl CoA

Formation of Acetyl CoA from

Pyruvic Acid

Remember, thereare 2 pyruvates perglucose molecule!

CO2

Pyruvic Acid

Acetyl CoA


Acetyl CoA

C - C - C - C

O O

OH

O

HO

Oxaloacetate (4-carbon)

Citrate(6-C)

NADH + H

NADH + H

NADH + H

CO2

CO2FADH2ATP

H3C - C - S - CoA

O

Remember... 2 of theseper molecule of glucose,so double the outputs ofthe TCA shown here.



One molecule of glucose yields...

• Glycolysis– 2 NADH – 2 ATP

• Pyruvate to Acetyl CoA conversion– 2 NADH (because there are 2 pyruvates)

• Citric Acid cycle (numbers are for 2 pyruvates going through)– 6 NADH– 2 FADH2

– 2 ATP

• Total: 10 NADH, 2 FADH2, and 4 ATP


Electron Transport, Making ATP

• Each NADH + H yields 2 electrons– Electron transport along the cytochrome chain enables

establishment of an electrochemical H+ gradient along the inner mitochondrial membrane.

• Hydrogen movement down this gradient, through the ATP synthetase, provides the energy for conversion of ADP to ATP.

• Each electron pair from each NADH + H can provide enough energy for production of 3 ATP– electron pair from FADH2 yield 2 ATP

Copyright © 2006 by Elsevier, Inc.Downloaded from: StudentConsult (on 1 March 2009 09:39 PM)

© 2005 Elsevier

Chemiosmosis


ATP Synthase


One molecule of glucose yields...

• Glycolysis– 2 NADH + 2H – 2 ATP

• Pyruvate to Acetyl CoA conversion– 2 NADH + 2H

• Citric Acid cycle– 6 NADH + 6H– 2 FADH2

– 2 ATP

• Total: 38 ATP, which yields ~ 456 kcal

6 ATP

6 ATP

18 ATP

4 ATP

Glucose

Galactose

Fructose

Glucose-6-P

Fructose-1,6-PP

Fructose-6-P

DHA-P

GA 3-P

Galactose-1-P Glucose-1-P

glucokinase (liver)

hexokinase

Fructose-1-P

fructokinase

galactokinase


Glucose

Galactose

Fructose

Glucose-6-P Fructose-6-P

Glucose-1-P

glucose-6-phosphatase

Because the liver has this enzyme, it can convert the othermonosaccharides into glucose for export. (Renal tubular andintestinal epithelial cells also have this enzyme)

Phosphorylation of the monosaccharides upon entering cells of thebody “traps” it there for use. The G-6-P enzyme is needed for tissuesthat send glucose to other parts of the body.Copyright © 2006 by Elsevier, Inc.

Glucose 1-P

Glucose 6-P

Glycolysis

UDP -Glucose

Glycogen

Glucose

FromGluconeogenesis

From the Blood

Glycogenesis &Glycogenolyis

Glycogenolysis

Glycogenesis



The Lactate Story

• The NADH formed from oxidizing glucose eventually gets oxidized back to NAD+ in the mitochondria.– (the result of giving the electrons to electron transport chain)

• NAD+ is needed to keep oxidizing glucose.• In exercise (once the anaerobic threshold is crossed),

NAD+ isn’t re-formed fast enough, so low levels threaten to stop glycolysis and ATP production.

• The main reason to form lactate is to regenerate the NAD+ needed to continue oxidizing glucose.

Glyceraldehyde - 3 - P

1,3 - Diphosphoglycerate

Lactate

Pyruvate

NAD+

NADH

(oxidized)

(reduced)

reductionreaction

oxidationreaction

GLYCOLYSIS



The Fate of Lactate

• Lactate is transported to the liver for conversion back to pyruvate and then, via gluconeogenesis, to glucose.– Why would muscle transport lactate to the liver for conversion back to

pyruvate? NAD+ is needed for that step, and the point of making lactate in the first place was because NAD+ was too low.

• Lactate is in a sense a “storage form” of NADH, because when it gets oxidized back to pyruvate, NADH is formed.

• The glucose is released and taken up by the active muscle.


More on Lactate

• Reconversion of Lactic Acid: Why does excess ATP cause excess pyruvate to be converted back to glucose?– This is because high ATP levels inhibit glycolysis and actually

promote the reverse, i.e. gluconeogenesis.

• Lactic Acid and the Heart– The very high blood flow and O2 levels mean no shortage of NAD+

so any lactate that is formed can be oxidized readily to pyruvate.– Significant lactic acid is formed in the heart only during ischemia.– Lactate Dehydrogenase (LD) has a very low affinity for pyruvate in the

heart, also explaining why little lactate is formed normally. However, cardiac LD has high affinity for lactate, hence the ability of the heart to utilize lactate from the circulation during exercise.

• in “white” skeletal muscle, LD has a high affinity for pyruvate.


Control of Glucose Oxidation

fructose 6-P fructose 1,6-diphosphate

Phosphofructokinase

ATP

ADPcitrateglucagon

Pyruvatekinase

NADH

Pyruvate

PEP

Acetyl CoA

pyruvate dehydrogenase

PyruvateMitochondrion

citrate formation(+ other steps)

+


Effects of Epinephrine and Glucagon

Glycogen Glucose-1-P

“Glucose” Glycogen

Glycogen SynthaseINACTIVEINACTIVE (D)

Epinephrine/Glucagon

cAMP-dependentprotein kinase

Inactivates this by adding

Activates this by adding

P

Phosphorylase aactive P

P

P

+

Phosphorylase aactive

Glycogen

Glucose-1- PPhosphorylase Phosphatase

active phosphorylase b kinase

Epinephrine/Glucagon

cAMP

Epinephrine and Glucagon stimulate glycogen breakdown ultimately by adding a to and activating glycogen phosphorylase (phosphorylase a).

Phosphorylase binactive

cAMP-dependentprotein kinase

Phosphorylates and activates this enzyme

P

PP

P



Final Enzymes for Glycogen -esis and -olysis

Glycogen Glucose-1-P

“Glucose” Glycogen

Phosphorylase aactive P

Glycogen Synthaseactive (I)

Glycogenolysis

Glycogenesis

Note that the enzyme for glycogenolysis is activated when itis phosphorylated (i.e. has a phosphate added ), but the enzyme for glycogenesis is inhibited by phosphorylation.

(Phosphorylase b is the inactive form)

P

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