Overview
Living organisms catabolize organic molecules within their cells and use
the energy released to manufacture ATP by phosphorylating ADP. Many prokaryotes
and virtually all eukaryotes phosphorylate ADP either through fermentation
(anaerobic) or respiration (aerobic). Both of these processes involve oxidation
of foodstuffs, yet only the latter requires oxygen.
The Role of Coenzymes
In metabolic pathways, coenzymes play a vital role. Metabolic enzymes operate
in the body's cells and blood. Metabolic enzymes facilitate the chemical
reactions that carry out the processes of metabolism. Typically, metabolic
enzymes are composed of two components: (1) an "apoenzyme" that identifies
which molecule within a cell requires a specific chemical reaction and (2)
a "coenzyme" that initiates the specific chemical reaction.
The body's primary sources of energy are produced at the cellular level by
metabolic processes. Coenzyme-A (CoA), Acetyl Coenzyme-A (acetyl CoA), Coenzyme Q10 (CoQ10) and Coenzyme 1 (NADH), together with certain B-vitamins and their
coenzyme forms are necessary for such energy production during: (1) the
tricarboxylic acid cycle (the TCA cycle, Krebs cycle, or citric acid cycle)
and (2) the glycolitic cycle.
Coenzyme-A is the most active metabolic enzyme in the human body. It operates
in the body's cells and blood where it initiates hundreds of important processes
in the body. Coenzyme-A passes out of the body and should be replenished
on a daily basis.
Coenzymes are chemicals synthesized by organisms from dietary vitamins. Coenzymes
are carriers of substances to and from enzyme-catalyzed reactions:
· NAD+ (oxidized form of nicotinamide adenine
dinucleotide) carries hydrogen and is derived from dietary niacin. It is
designated as NADH + H+ (sometimes NADH2) when it is
in the reduced form. Recall that the reduced form is the energetically valuable
one, whereas the oxidized form is the energy poor one. A structurally similar
coenzyme, NADP+, is important in photosynthesis and other cellular
phenomena.
· FAD (oxidized form of flavin adenine dinucleotide) carries
hydrogen and is derived from riboflavin. It is designated FADH2
when it is in the reduced form.
· CoA (Coenzyme-A) carries an acetyl group to the site of the
Krebs Cycle; it is derived from pantothenic acid. It may also carry a succinyl
group. When combined, it is called acetyl (or succinyl) CoA.
Glycolysis
During glycolysis, the potential energy of a primary foodstuff, glucose,
is released during a series of chemical reactions which occur in the cytoplasm.
Some of the energy released when bonds are broken is used to phosphorylate
ADP and some is transferred to a coenzyme, NAD+, which is reduced
to NADH + H+. No oxygen is used during glycolysis. Pyruvate, a
product of glycolysis may either be converted to lactate or ethanol
(fermentation) or be converted to an acetyl group for further processing
during the Krebs cycle.
Fermentation
Fermentation is a process whereby a cell can achieve redox balance (reoxidizing
NADH + H+ which was produced in glycolysis), thus allowing for
the oxidation of additional glucose during glycolysis. Two types of fermentation
occur, one in yeast and one in muscle cells when oxygen is not available
in adequate amounts to allow for oxidative phosphorylation. In the first
process, the pyruvate resulting from glycolysis is converted to acetaldehyde
then ethanol; in the second, the pyruvate is converted to lactic acid.
Krebs Cycle (TCA Cycle or Citric Acid Cycle)
If oxygen is available to support aerobic respiration, reactions occur subsequent
to glycolysis within the mitochondrion (especially associated with the inner
mitochondrial membrane). The first event to occur is oxidation of pyruvate
to acetyl, which then combines with Coenzyme-A to yield acetyl CoA. Next,
Coenzyme-A delivers the acetyl group to oxaloacetate (OXA), a four carbon
compound already present in the mitochondrion, with which the 2 carbon acetyl
group combines to form citric acid. This step initiates the "first turn"
of the Krebs Cycle. At the end of the Krebs Cycle, oxaloacetate has once
again been formed. A second acetyl CoA combines with it, initiating the second
turn of the Krebs Cycle.
After the second cycle has been completed, the original glucose has been
turned into a total of 6 CO2 molecules yet no oxygen has been
used. Only 4 ATP molecules have been netted.
Oxidative Phosphorylation
This process occurs on the plasma membrane of prokaryote cells and on the
inner membrane of the mitochondrion; quantitatively, it is the most important
way that ATP is made by aerobic cells. During the process, the coenzymes
(NADH + H+ and FADH2) which have accumulated during
previous processes transfer hydrogen atoms to components of the electron
transport chain. During transport, hydrogens and electrons are transferred
to acceptors in such a way that protons are pumped across the inner mitochondrial
membrane. This results in an electrochemical gradient which is later used
to phosphorylate ADP as protons diffuse back across the membrane. Hence,
oxidative phosphorylation results from a process of chemiosmosis. In the
final step of this sequence, electrons are transferred to oxygen and used
in the formation of water.
Energy Yield
ATP molecules are made from the following: 2 from glycolysis, 2 from the
Krebs cycle, 4 ATP from NADH + H+ during chemiosmosis from glycolysis,
6 from pyruvate oxidation, 18 from the Krebs cycle, 4 ATP from
FADH2 during chemiosmosis from the Krebs cycle. TOTAL = 36 ATP
molecules.
In eukaryotic cells, the reduced NADH + H+ produced during glycolysis
is actively transported into the mitochondrion, at a cost of 2 ATP molecules.
Hence, the "energy yield" from that coenzyme is only 2 ATP molecules per
NADH + H+, rather than 3 ATP molecules (as is the case for NADH
+ H+ produced within the mitochondrion). In prokaryotic cells,
active transport into the mitochondrion does not occur, as chemiosmosis occurs
at the plasma membrane. Hence, the energy yield for respiration in bacteria
is 38 ATP molecules.
Other Metabolic Substrates
Although the discussion here has emphasized the central role of glucose as
a metabolic substrate during cellular metabolism, it is important to note
that metabolic pathways utilize other metabolic substrates.
Anabolic and Catabolic Pathways
The figure below shows potential interactions between
Anabolic and Catabolic Pathways in Cellular Metabolism
In living cells catabolism involves exergonic reactions which tend to release energy which is used to phosphorylate ADP. In the figure above, such pathways are shown to involve various types of biomolecules (arrows directed downward). Anabolic pathways incorporate energy in processes which tend to synthesize larger molecules (arrows directed upward). Hence, although most of the discussion of cellular metabolism focused on catabolism of glucose, alternative metabolic substrates (e.g., amino acids and fatty acids) may also be used as sources of energy.
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