139
CHAPTER FOUR
Cellular Metabolism
4.4
FROM SCIENCE TO TECHNOLOGY
The Human Metabolome
A
generation ago, prehealth profession stu-
dents had to memorize a frighteningly
complex chart of biochemical pathways
that represent all of the energy reactions in a cell.
The cellular respiration pathways ran down the cen-
ter, with branches radiating outward and in some
places interconnecting into a giant web. Today,
several technologies as well as the ability to store
massive amounts of data have made possible the
Human Metabolome Database (
www.hmdb.ca
).
“Metabolome” refers to all of the small mol-
ecules that are part of metabolism in a cell, tis-
sue, organ, or an entire organism. The database
is a vast, annotated catalog of those molecules.
The government of Canada is supporting the
effort to search all published papers and books
that describe metabolites and link that infor-
mation with experimental data. The techniques
of electrophoresis and chromatography are
used to separate metabolites, and mass spec-
trometry (MS) and nuclear magnetic resonance
(NMR) spectroscopy describe their chemical
characteristics.
Biochemists estimate that human cells have
at least 2,500 different metabolites, but fewer
than half have been identified. Far fewer have
been analyzed for their concentrations in di±
er-
ent cell types under different conditions. In the
Human Metabolome Database, each entry has
an electronic “MetaboCard” that includes 90 data
²
elds, half with clinical data (such as associated
diseases and drug interactions) and half with bio-
chemical data (such as pathways and enzymes
that interact with the metabolite). Each entry is
also hyperlinked to other databases, interfacing
with 1,500 drugs and 3,600 foods and food addi-
tives. The information in the Human Metabolome
Database is being used in drug discovery, toxicol-
ogy, transplant monitoring, clinical chemistry,
disease diagnosis, and screening of newborns for
metabolic disorders.
The “metabolome” is one of several “omes”
now under intense study. The ²
rst was “genome,”
coined in 1920 to denote a complete set of genes.
It was joined much more recently by “proteome”
to denote the proteins in a cell or organism, and
then “transcriptome” to list the RNA molecules
in a cell type. The “omes” comprise the new ²
eld
of systems biology, which examines the interac-
tions and relationships among the parts of an
organism. The genome, proteome, and transcrip-
tome each describe a single type of molecule.
The metabolome is the most complex set of bio-
chemicals in a cell or organism.
4. Factors that alter enzymes
a. Enzymes are proteins and can be denatured.
b. Factors that may denature enzymes include heat,
radiation, electricity, chemicals, and extreme pH
values.
4.4
ENERGY FOR METABOLIC REACTIONS
(PAGE 119)
Energy is a capacity to produce change or to do work.
Common forms of energy include heat, light, sound,
electrical energy, mechanical energy, and chemical energy.
Metabolic energy is made available by the reactions of
cellular respiration.
1. ATP molecules
a. Energy is captured in the bond of the terminal
phosphate of each ATP molecule.
b. Captured energy is released when the terminal
phosphate bond of an ATP molecule breaks.
c. ATP that loses its terminal phosphate becomes ADP.
d. ADP can be converted to ATP by capturing energy
and a phosphate.
e. ATP is the primary energy-carrying molecule in a
cell.
2. Release of chemical energy
a. Most metabolic processes use chemical energy
released when molecular bonds break.
b. The energy glucose releases during cellular
respiration is used to promote metabolism.
c. Enzymes in the cytoplasm and mitochondria
control cellular respiration.
1. Enzyme action
a. Metabolic reactions require energy to start.
b. Enzymes are proteins that increase the rate of
speci±
c metabolic reactions.
c. An enzyme acts when its active site temporarily
combines with the substrate, altering its chemical
structure. This enables the substrate to react,
forming a product. The enzyme is released in its
original form.
d. The rate of enzyme-controlled reactions depends
upon the numbers of enzyme and substrate
molecules and the ef±
ciency of the enzyme.
e. Enzymes are usually named according to their
substrates, with
-ase
at the end.
2. Regulation of metabolic pathways
a. A rate-limiting enzyme may regulate a metabolic
pathway.
b. A negative feedback mechanism in which the
product of a pathway inhibits the regulatory
enzyme may control the regulatory enzyme.
c. The rate of product formation usually remains
stable.
3. Cofactors and coenzymes
a. Cofactors are additions to some enzymes that are
necessary for their function.
b. A cofactor may be an ion or a small organic
molecule called a coenzyme.
c. Vitamins, the sources of coenzymes, usually
cannot be synthesized by human cells in adequate
amounts.
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