Metabolism an Overviewto accompany Biochemistry

Biochemistry 2/e - Garrett & Grisham

Chapter 18
Metabolism--an Overview
to accompany
Biochemistry, 2/e
by
Reginald Garrett and Charles Grisham
All rights reserved. Requests for permission to make copies of any part of the work
should be mailed to: Permissions Department, Harcourt Brace & Company,
6277
Sea Harbor Drive, Orlando, Florida 32887-6777
Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Outline
•
•
•
•
•

18.1 Basic Set of Metabolic Pathways
18.2 Catabolism and Anabolism
18.3 Experimental Methods
18.4 Nutrition
SPECIAL FOCUS: Vitamins

Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

Metabolism
• The sum of the chemical changes that
convert nutrients into energy and the
chemically complex products of cells
• Hundreds of enzyme reactions organized
into discrete pathways
• Substrates are transformed to products
via many specific intermediates
• Metabolic maps portray the reactions
Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

A Common Set of Pathways
• Organisms show a marked similarity in
their major metabolic pathways
• Evidence that all life descended from a
common ancestral form
• There is also significant diversity
• Autotrophs use CO2; Heterotrophs use
organic carbon; Phototrophs use light;
Chemotrophs use Glc, inorganics & S
Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

The Sun is Energy for Life
• Phototrophs use light to drive synthesis
of organic molecules
• Heterotrophs use these as building
blocks
• CO2, O2, and H2O are recycled
• See Figure 18.3

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Metabolism
• Metabolism consists of catabolism and
anabolism
• Catabolism: degradative pathways
– Usually energy-yielding!

• Anabolism: biosynthetic pathways
– energy-requiring!

Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Organization in Pathways
•
•
•
•
•

Pathways consist of sequential steps
The enzymes may be separate
Or may form a multienzyme complex
Or may be a membrane-bound system
New research indicates that
multienzyme complexes are more
common than once thought

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

Catabolism and Anabolism
• Catabolic pathways converge to a few
end products
• Anabolic pathways diverge to
synthesize many biomolecules
• Some pathways serve both in
catabolism and anabolism
• Such pathways are amphibolic
Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Comparing Pathways
• Anabolic & catabolic pathways involving
the same product are not the same
• Some steps may be common to both
• Others must be different - to ensure that
each pathway is spontaneous
• This also allows regulation mechanisms
to turn one pathway on and the other off

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

The ATP Cycle
• ATP is the energy currency of cells
• Phototrophs transform light energy into
the chemical energy of ATP
• In heterotrophs, catabolism produces
ATP, which drives activities of cells
• ATP cycle carries energy from
photosynthesis or catabolism to the
energy-requiring processes of cells
Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

Redox in Metabolism
• NAD+ collects electrons released in
catabolism
• Catabolism is oxidative - substrates lose
reducing equivalents, usually H - ions
• Anabolism is reductive - NADPH
provides the reducing power (electrons)
for anabolic processes

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

A comparison of state of reduction of
carbon atoms in biomolecules.

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Isotope Tracers as Probes
• Substrates labeled with an isotopic form
of some element can be fed to cells and
used to elucidate metabolic sequences

• Radioactive isotopes: 14C, 3H, 32P
ã Stable heavy isotopes: 18O, 15N

Copyright â 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Nutrition
• Protein is a rich source of nitrogen and
also provides essential amino acids
• Carbohydrates provide needed energy
and essential components for
nucleotides and nucleic acids
• Lipids provide essential fatty acids that
are key components of membranes and
also important signal molecules
Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Vitamins
• Many vitamins are "coenzymes" molecules that bring unusual chemistry
to the enzyme active site
• Vitamins and coenzymes are classified
as "water-soluble" and "fat-soluble"
• The water-soluble coenzymes exhibit
the most interesting chemistry
Copyright © 1999 by Harcourt Brace & Company

Biochemistry 2/e - Garrett & Grisham

Vitamin B1
•
•
•
•

Thiamine pyrophosphate (TPP)
Thiamine - a thiazole ring joined to a
substituted pyrimidine by a methylene bridge
Thiamine-PP is the active form
TPP is involved in carbohydrate metabolism
It catalyzes decarboxylations of alpha-keto
acids and the formation and cleavage of
alpha-hydroxyketones

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Copyright © 1999 by Harcourt Brace & Company


Biochemistry 2/e - Garrett & Grisham

Thiamine Pyrophosphate

•
•

•
•

Reactions and rationale
Yeast pyruvate decarboxylase, acetolactate
synthase, transketolase, phosphoketolase
All these reactions depend on accumulation
of negative charge on the carbonyl carbon at
which cleavage occurs!
Thiamine pyrophosphate facilitates these
reactions by stabilizing this negative charge
The key is the quaternary nitrogen of the
thiazolium group
Copyright © 1999 by Harcourt Brace & Company