Page 28 - 84 human physiolofy part-1

Chapter 2

interior of the mitochondrion. Once the pyruvic acid is inside, carbon dioxide is enzymatically removed
from each three-carbon pyruvic acid molecule to form acetic acid. The enzyme then combines the
acetic acid with an enzyme, coenzyme A, to produce acetyl coenzyme A, also known as acetyl CoA.

Once acetyl CoA is formed, the Krebs cycle begins. The cycle is split into eight steps, each of
which will be explained below.

• Step 1: The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a
molecule of citrate. The acetyl coenzyme A acts only as a transporter of acetic acid from one
enzyme to another. After Step 1, the coenzyme is released by hydrolysis so that it may combine
with another acetic acid molecule to begin the Krebs cycle again.

• Step 2: The citric acid molecule undergoes an isomerization. A hydroxyl group and a
hydrogen molecule are removed from the citrate structure in the form of water. The two carbons
form a double bond until the water molecule is added back. Only now, the hydroxyl group and
hydrogen molecule are reversed with respect to the original structure of the citrate molecule.
Thus, isocitrate is formed.

• Step 3: In this step, the isocitrate molecule is oxidized by a NAD molecule. The NAD
molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a
hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure
is very unstable, so a molecule of CO is released creating alpha-ketoglutarate.
2

• Step 4: In this step, our friend, coenzyme A, returns to oxidize the alpha-ketoglutarate
molecule. A molecule of NAD is reduced again to form NADH and leaves with another
hydrogen. This instability causes a carbonyl group to be released as carbon dioxide and a
thioester bond is formed in its place between the former alpha-ketoglutarate and coenzyme A to
create a molecule of succinyl-coenzyme A complex.

• Step 5: A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating
phosphate group displaces coenzyme A and forms a bond with the succinyl complex. The
phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It
leaves behind a molecule of succinate.

• Step 6: In this step, succinate is oxidized by a molecule of FAD (Flavin adenine
dinucleotide). The FAD removes two hydrogen atoms from the succinate and forces a double
bond to form between the two carbon atoms, thus creating fumarate.

• Step 7: An enzyme adds water to the fumarate molecule to form malate. The malate is
created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a
carbon next to a terminal carbonyl group.

• Step 8: In this final step, the malate molecule is oxidized by a NAD molecule. The carbon
that carried the hydroxyl group is now converted into a carbonyl group. The end product is
oxaloacetate which can then combine with acetyl-coenzyme A and begin the Krebs cycle all
over again.

• Summary: In summary, three major events occur during the Krebs cycle. One GTP
(guanosine triphosphate) is produced which eventually donates a phosphate group to ADP to

28 | Human Physiology