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Anabolism: The Use of Energy in Biosynthesis
CHAPTER OVERVIEW
This chapter presents an overview of anabolism starting with the fixation of carbon dioxide. It then focuses on
the synthesis of carbohydrates and peptidoglycan; the assimilation of phosphorus, sulfur, and nitrogen; and the
synthesis of amino acids, purines and pyrimidines, and lipids.
CHAPTER OBJECTIVES
After reading this chapter you should be able to:
•
•
•
•
•
•
discuss the use of energy to construct more complex molecules and structures from smaller, simpler
precursors
discuss the way that biosynthetic pathways are organized to conserve genetic storage space, biosynthetic
raw materials, and energy
discuss the way that autotrophs use ATP and NADPH (or NADH) to reduce carbon dioxide and
incorporate it into organic material
describe the assimilation of phosphorus, sulfur, and nitrogen
discuss the use of the TCA cycle as an amphibolic pathway and the need for anaplerotic reactions to
maintain adequate levels of TCA cycle intermediates
discuss the synthesis of glucose (gluconeogenesis) and other carbohydrates, fatty acids, triacylglycerols,
purines and pyrimidines, and amino acids
CHAPTER OUTLINE
I.
II.
Introduction
A. Anabolism—the creation of order by the synthesis of complex molecules from simpler ones; it
requires the input of energy
B. Turnover—the continual degradation and resynthesis of cellular constituents
C. The rate of biosynthesis is approximately balanced by that of catabolism, due to careful regulation
of metabolic processes
Principles Governing Biosynthesis
A. Biosynthetic metabolism follows a few general principles:
1. The synthesis of large, complex molecules (macromolecules) from a limited number of simple
structural units (monomers) saves much genetic storage capacity, biosynthetic raw material,
and energy
2. The use of many of the same enzymes for both catabolism and anabolism saves additional
materials and energy
3. Many biosynthetic pathways are reversals of catabolic pathways; many steps of the pathway
are catalyzed by enzymes that participate in both catabolic and anabolic activities; however,
some steps are catalyzed by two different enzymes: one that functions in the catabolic direction
and a second that functions in the biosynthetic direction; this permits independent regulation of
catabolism and anabolism
4. Coupling some biosynthetic reactions with the breakdown of ATP (or other nucleoside
triphosphates) drives anabolic pathways irreversibly in the direction of biosynthesis
5. In eukaryotic cells, anabolic and catabolic reactions involving the same constituents are
frequently located in separate compartments for simultaneous but independent operation
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6.
Catabolic and anabolic pathways use different cofactors: catabolic oxidations produce NADH,
which is a substrate for electron transport, while NADPH acts as an electron donor for
anabolic pathways
B. Once macromolecules have been made from simpler precursors, cell structures (e.g., ribosomes)
form spontaneously from the macromolecules by a process known as self-assembly
III. Precursor Metabolites
A. Precursor metabolites are carbon skeletons used as building blocks for the synthesis of
macromolecules; many are intermediates in glycolytic pathways and the TCA cycle
IV. CO2 Fixation
A. Autotrophs use CO2 as their sole or principal carbon source; carbon fixation requires much energy
and reducing power
B. Calvin cycle
1. The most widely used carbon fixation pathway is the Calvin cycle (reductive pentose
phosphate cycle or Calvin-Benson cycle); it consists of three phases that occur in the
chloroplast stroma of eukaryotes and possibly in the carboxysomes of certain bacteria
2. The carboxylation phase—the enzyme ribulose 1,5-bisphosphate carboxylase oxygenase
(Rubisco) catalyzes the addition of carbon dioxide to ribulose 1,5-bisphosphate, forming two
molecules of 3-phosphoglycerate
3. The reduction phase—3-phosphoglycerate is reduced to glyceraldehyde 3-phosphate
4. The regeneration phase—a series of reactions is used to regenerate ribulose 1,5-bisphosphate
and to produce carbohydrates such as fructose and glucose; this phase is similar to the pentose
phosphate pathway and involves transketolase and transaldolase reactions
5. The incorporation of one carbon dioxide takes three ATP molecules and two NADPH
molecules; thus the formation of a single glucose molecule requires six turns through the cycle
with an expenditure of 18 ATP molecules and 12 NADPH molecules; sugars formed in the
Calvin cycle can then be used to synthesize other essential molecules
C. Other CO2-fixation pathways are used by some bacteria and archaea including the reductive TCA
cycle, the 3-hydroxypropionate cycle, the acetyl-CoA pathway, and the 3-hydroxypropionate/4hydroxybutyrate pathway
V. Synthesis of Sugars and Polysaccharides
A. Synthesis of monosaccharides
1. Heterotrophs synthesize glucose from noncarbohydrate precursors in a process called
gluconeogenesis; this pathway is a functional reversal of glycolysis—it shares seven enzymes
with the glycolytic pathway, reversing their catabolic direction, and uses several distinct
enzymes or multi-enzyme systems to catalyze steps that cannot be directly reversed
2. Once glucose and fructose are synthesized by gluconeogenesis, other sugars are manufactured;
several of these other sugars are synthesized while attached to a nucleoside diphosphate
B. Synthesis of polysaccharides also requires the use of nucleoside diphosphate sugars as precursors
C. Synthesis of peptidoglycan
1. A multistep process that involves two carriers: uridine diphosphate and bactoprenol; during the
process a peptidoglycan repeat unit is formed and is attached to the growing peptidoglycan
chain after being transported across the cytoplasmic membrane; cross-links are then formed by
transpeptidation
2. Autolysins carry out limited digestion of peptidoglycan, and provide acceptor ends for the
addition of new peptidoglycan units
3. Peptidoglycan synthesis is very vulnerable to disruption by antimicrobial agents, including
antibiotics such as penicillin; inhibition of any step in the process weakens the cell wall and
can cause lysis
VI. Synthesis of Amino Acids
A. Nitrogen assimilation
1. Ammonia incorporation
a. Many microorganisms use reductive amination to make alanine and glutamate, which are
then used as sources of amino groups; the amino groups are transferred from alanine or
glutamate to other carbon skeletons by transamination reactions
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b.
Other microorganisms use the enzymes glutamine synthetase and glutamate synthase to
synthesize glutamate, which then acts as an amino group donor in transaminase reactions
2. Assimilatory nitrate reduction involves the reduction of nitrate to nitrite, then to
hydroxylamine, and finally to ammonia, which can then be incorporated by the routes
described above
3. Nitrogen fixation is the reduction of atmospheric nitrogen to ammonia; this is catalyzed by the
enzyme nitrogenase, which is found in only a few species of bacteria, archaea, and
cyanobacteria; nitrogen fixation requires an expenditure of 16 ATP molecules and 8 electrons
per N2 reduced; the ammonia produced can be incorporated into organic molecules by the
processes described above
B. Sulfur assimilation
1. Organic sulfur in the form of cysteine and methionine can be obtained from external sources
2. Assimilatory sulfate reduction is used to reduce inorganic sulfate before it is incorporated into
cysteine
C. Amino acid biosynthetic pathways
1. Involves attachment of an amino group to a carbon skeleton
2. Carbon skeletons are derived from acetyl-CoA and from intermediates of the TCA cycle,
glycolysis, and the pentose phosphate pathway
D. Anaplerotic reactions and amino acid biosynthesis
1. Biosynthetic functions of the TCA cycle are so important that many of its intermediates must
be synthesized even when the TCA cycle is not functioning to catabolize pyruvate or to
provide NADH for electron transport
2. Anaplerotic reactions replenish TCA cycle intermediates so that biosynthesis can occur; two
major types of anaplerotic reactions have been observed
a. Anaplerotic carbon dioxide fixation (e.g., pyruvate carboxylase reaction)
b. Glyoxylate cycle—used by microorganisms that can grow on acetate as a sole carbon
source; is a modified TCA cycle where carbons entering the cycle are not released as
carbon dioxide
VII. Synthesis of Purines, Pyrimidines, and Nucleotides
A. These molecules are critical for all cells because they are used in the synthesis of ATP, several
cofactors, RNA, and DNA; two types of bases are required: purines (adenine and guanine) and
pyrimidines (uracil, cytosine, and thymine); a nucleoside includes the base and sugar, while a
nucleotide also has the phosphate group
B. Phosphorus assimilation
1. Inorganic phosphates are incorporated through the formation of ATP by
photophosphorylation, oxidative phosphorylation, and substrate-level phosphorylation
2. Organic phosphates obtained from the surroundings are hydrolyzed to release inorganic
phosphates by enzymes called phosphatases
C. Purine biosynthesis is a complex pathway in which seven different molecules (including folic acid)
contribute parts to the final purine skeleton; the first purine product is the nucleotide inosinic acid,
from which all other purine nucleotides can be made
D. Pyrimidine biosynthesis starts with aspartic acid and carbamoyl phosphate forming the initial
pyrimidine product (orotic acid), which can then be converted to pyrimidine nucleotides
VIII. Lipid Synthesis
A. Fatty acid synthesis is catalyzed by fatty acid synthetase using the substrates acetyl-CoA and
malonyl-CoA, the electron donor NADPH, and a small protein called acyl carrier protein (ACP),
which carries the growing fatty acid chain; the fatty acid is lengthened by adding two carbons at a
time to its carboxyl end
B. Triacylglycerols are formed from the reduction of dihydroxyacetone phosphate (a glycolytic
pathway intermediate) to glycerol 3-phosphate, which then undergoes esterification with two fatty
acids to form phosphatidic acid; this can then be used to produce triacylglycerol
C. Phospholipids also are produced from phosphatidic acid using a cytidine diphosphate (CDP) carrier
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TERMS AND DEFINITIONS
____ 1.
____ 2.
____ 3.
____ 4.
____ 5.
____ 6.
____ 7.
____ 8.
____ 9.
The process by which cellular molecules and
constituents are continually being degraded and
resynthesized
Very large molecules that are polymers of smaller units
A pathway used by autotrophs to incorporate carbon
dioxide into carbohydrate
The synthesis of glucose from noncarbohydrate
precursors
The reduction of atmospheric gaseous nitrogen to
ammonia
Reactions that replenish any TCA cycle intermediates
that have been used in biosynthetic reactions
Enzymes that digest peptidoglycan just enough to
provide acceptor ends for incorporation of new
peptidoglycan units
Enzyme that releases inorganic phosphate from organic
phosphate
An intermediate in assimilatory sulfate reduction
a.
b.
c.
d.
e.
f.
g.
h.
i.
anaplerotic reactions
autolysins
Calvin cycle
gluconeogenesis
macromolecules
nitrogen fixation
phosphatase
phosphoadenosine 5′phosphosulfate
turnover
FILL IN THE BLANK
1.
2.
3.
4.
5.
6.
7.
8.
9.
Nitrogenous bases are either purines or pyrimidines. The purines are
and
.
The pyrimidines are
,
, and
.
The
system is used to synthesize
from acetyl-CoA,
malonyl-CoA, and NADPH. During synthesis, the intermediates are attached to the
protein.
The cell saves energy and materials by using many of the same enzymes for both ____________ and
____________. However, some steps are catalyzed by different enzymes to allow
of the two processes.
After macromolecules have been constructed from simpler precursors, they are assembled into supramolecular complexes or organelles by a process known as
.
The three phases of the Calvin cycle are the ____________ phase, the ____________ phase, and the
____________ phase. The initial phase is catalyzed by the enzyme
.
The photosynthetic production of one molecule of glucose requires ______ molecules of ATP and
______ molecules of NADPH, which are provided by the ____________ reactions of photosynthesis.
The reduction of sulfate for use in the production of such compounds as the amino acid cysteine is called
____________ sulfate reduction, while the reduction of sulfate as a terminal electron acceptor during
anaerobic respiration is called ____________ sulfate reduction.
Ammonia is assimilated by the activity of enzymes that catalyze reductive amination. Two important
reductive amination reactions are catalyzed by alanine dehydrogenase and
, which
synthesize alanine from pyruvate and
from α-ketoglutarate, respectively. Once these amino
acids are made, their amino group can be transferred to other carbon skeletons by enzymes called
Another route for ammonia incorporation involves the sequential action of
and
, followed by the transfer of amino groups to other carbon
skeletons by
. Nitrate and nitrogen gas can also serve as nitrogen sources. Nitrate is incorporated
through
nitrate reduction, which is catalyzed by the enzymes
and
. Nitrogen gas can be used by just those few microorganisms capable of
carrying out
, which is catalyzed by the enzyme
.
Biosynthesis of purines and pyrimidines is critical for all cells since these molecules are used in the
synthesis of _______, _______, and _________, as well as several cofactors and other important cellular
components.
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.
10. A purine or pyrimidine base joined with a pentose sugar, either ____________ or ____________, is a
____________. If one or more phosphate groups are attached to the sugar, it is called a ____________.
11. Microorganisms synthesize various carbohydrates using the
pathway. Glucose, fructose,
and mannose are either intermediates of the pathway or are made from its intermediates. Other sugars and
polysaccharides are made while attached to nucleoside diphosphates. One of the most important
nucleoside diphosphate sugars is
(UDPG).
12. Lipids called
are made from
and glycerol phosphate by a pathway in
which
is an important intermediate.
13. Synthesis of
involves UDP derivatives and a lipid carrier called
. This carrier
transports N-acetyl muramic acid (NAM)–N-acetyl glucosamine (NAG)–pentapeptide units across the
cell membrane. Cross-links are formed by
.
14. The reduction of carbon dioxide to organic compounds is called
.
Heterotrophic organisms use
reactions to do this, for the purpose of replenishing TCA
cycle intermediates. Only
do this as the principal method of fulfilling their carbon needs.
MULTIPLE CHOICE
For each of the questions below select the one best answer.
1.
2.
3.
Polymers are large molecules composed of
smaller units joined together. What are the
smaller units called?
a. monomers
b. micromolecules
c. multimers
d. macromolecules
How do cells independently regulate anabolic
and catabolic pathways?
a. by using separate enzymes for reversal
of key steps
b. by compartmentation of anabolic and
catabolic pathways
c. by using different cofactors for anabolic
and catabolic pathways
d. All of the above are ways in which cells
independently regulate anabolic and
catabolic pathways.
Which of the following is NOT assimilated
or incorporated in large quantities into
organic molecules?
a. nitrogen
b. sodium
c. phosphorus
d. sulfur
4.
5.
6.
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Which of the following is NOT used to
assimilate inorganic phosphate?
a. oxidative phosphorylation
b. substrate-level phosphorylation
c. periplasmic phosphorylation
d. photophosphorylation
Which of the following is NOT a source of
the carbon skeletons used in the synthesis of
amino acids?
a. acetyl-CoA
b. TCA cycle
c. glycolysis
d. All of the above are sources of carbon
skeletons for the synthesis of amino
acids.
Which reactions are used to replace TCA
cycle intermediates so that the TCA cycle can
continue to function when active biosynthesis
is taking place?
a. anaplerotic reactions
b. amphibolic reactions
c. anabolic reactions
d. catabolic reactions
7.
8.
In which of the following ways are the
anaplerotic CO2 fixation reactions of
heterotrophs different from the CO2 fixation
reactions found in autotrophs?
a. They usually use pyruvate as the
acceptor molecule rather than ribulose
1,5-bisphosphate.
b. They are used to replenish TCA cycle
intermediates and maintain metabolic
balance rather than providing carbon
for growth.
c. Both (a) and (b) are correct.
d. Neither (a) nor (b) is correct.
Cyanobacteria, some nitrifying bacteria, and
thiobacilli have polyhedral inclusion bodies
that contain the enzyme ribulose 1,5bisphosphate carboxylase. These are thought
to be the site of CO2 fixation in these
organisms. What are these inclusion bodies
called?
a. fixosomes
b. carboxysomes
c. plastosomes
d. chloroplasts
9.
Which of the following is true about the
synthesis of macromolecules from
monomeric subunits?
a. It saves genetic storage capacity.
b. It saves biosynthetic raw materials.
c. It saves energy.
d. All of the above are true.
TRUE/FALSE
____ 1.
The process of linking a few monomers together with a single type of covalent bond makes the
synthesis of macromolecules an inefficient process.
____ 2. In eukaryotic microorganisms, biosynthetic pathways are frequently located in cellular
compartments that are different from those in which their corresponding catabolic pathways are
located; this makes it easier for simultaneous but independent operation.
____ 3. Most microorganisms have the ability to incorporate or fix carbon dioxide, but only autotrophs can
use carbon dioxide as their sole or principal source of carbon.
____ 4. Nitrogen fixation does not require the expenditure of much energy.
____ 5. The enzyme nitrogenase is not highly specific and can reduce a number of compounds containing
triple bonds, such as acetylene, cyanide, and azide.
____ 6. Both purines and pyrimidine nucleotides are synthesized by first synthesizing the nitrogenous base
and then adding ribose 5-phosphate to form the nucleotide.
____ 7. Unsaturated fatty acids are those containing one or more carbon-carbon double bonds.
____ 8. Membrane phospholipids are constructed from the products of glycolysis, fatty acid biosynthesis,
and amino acid biosynthesis.
____ 9. Because peptidoglycan lies outside of the cytoplasmic membrane, all of the steps in its synthesis
must take place outside the membrane.
____ 10. Nitrogen fixation can consume up to 20% of the ATP generated by the host plant.
____ 11. Phosphorus can be obtained from both inorganic and organic phosphates.
____ 12. The glyoxylate cycle is a modified TCA cycle that is used to synthesize TCA intermediates.
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CRITICAL THINKING
1.
What would be the consequences for a cell if anaplerotic reactions did not exist? Consider in your
discussion the interrelationship between catabolic and anabolic reactions and the needs of an organism
growing on limited nutritional sources.
2.
There are a number of different ways to assimilate nitrogen. Only a relatively few species of bacteria,
however, are capable of utilizing gaseous atmospheric nitrogen (nitrogen fixation). Why do you think
such a variety of assimilatory pathways exist? Why do you think so few organisms are equipped to use
gaseous atmospheric nitrogen, even though it is quite abundant?
3.
Biosynthetic processes (e.g., gluconeogenesis) frequently are not direct reversals of the related catabolic
processes (e.g., glycolysis). However, some of the steps involved in the overall pathway may be direct
reversals. What is the advantage to the organism to have separate pathways for synthesis and
degradation? Furthermore, what is the advantage to the organism for the substantial overlap (i.e., directly
reversed steps) within these pathways?
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ANSWER KEY
Terms and Definitions
1. i, 2. e, 3. c, 4. d, 5. f, 6. a, 7. b, 8. g, 9. h
Fill in the Blank
1. adenine; guanine; thymine; cytosine; uracil 2. fatty acid synthetase; fatty acids; acyl carrier 3. catabolism;
anabolism; independent regulation 4. self-assembly 5. carboxylation; reduction; regeneration; ribulose 1,5bisphosphate carboxylase 6. 18; 12; light 7. assimilatory; dissimilatory 8. glutamate dehydrogenase; glutamate;
transaminases; glutamine synthetase; glutamate synthase; transaminases; assimilatory; nitrate reductase; nitrite
reductase; nitrogen fixation; nitrogenase 9. ATP; RNA; DNA 10. ribose; deoxyribose; nucleoside; nucleotide
11. gluconeogenesis; uridine diphosphate glucose 12. triacylglycerols; fatty acids; phosphatidic acid 13.
peptidoglycan; bactoprenol; transpeptidation 14. carbon dioxide fixation; anaplerotic; autotrophs
Multiple Choice
1. a, 2. d, 3. b, 4. c, 5. d, 6. a, 7. c, 8. b, 9. d
True/False
1. F, 2. T, 3. T, 4. F, 5. T, 6. F, 7. T, 8. T, 9. F, 10. T, 11. T, 12. T
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