CLINICAL CASES
191
A PPR O A C H TO O X ID A TIV E PH O SPH O R Y L A T IO N
A N D LACTATE
O bjectives
1.
Understand how hypoxemia (e.g., rhabdomyolysis) leads to reduced
oxidative phosphorylation and increased lactic acid production.
2.
Be familiar with the pyruvate cycle and the importance of NADH levels.
3.
Know about the lactic acid pathway.
D efinitions
Anion gap: A calculation of the routinely measured cations minus the rou-
tinely measured anions. Since in all fluids the sum of the positive
charges (cations) must be balanced with the negative charges (anions),
the anion gap is an artifact of measurement. Because the [K+] is small,
it is usually omitted from the calculation. The equation most frequently
used to calculate the anion gap is
AG = [Na+] - ([Cl-] + [HCO3-])
Gluconeogenesis: The series of biochemical reactions in which glucose is
synthesized in the liver (and other gluconeogenic tissues) from small
organic acids such as lactate, pyruvate, and oxaloacetate.
Hematin: Heme in which the coordinated iron is in the ferric (Fe3+) oxida-
tion state.
Myoglobin: A large heme-containing protein that is able to bind oxygen
and release it in tissues in which the oxygen tension is low.
b-Oxidation: The series of biochemical reactions in which fatty acids are
degraded to acetyl-CoA, which then enters the tricarboxylic acid cycle
for the production of energy in the form of reducing equivalents and
GTP. Each round of P-oxidation shortens the fatty acid by two carbons
and, in addition to acetyl-CoA, produces NADH and FADH2, which are
fed into the electron transport system for the production of ATP.
D ISC U SSIO N
The exercising muscle’s sources of energy are primarily glucose and fatty
acids. The muscle obtains glucose from the blood or the breakdown of stored
glycogen in the muscle. Fatty acids are acquired as free fatty acids from the
blood or from the breakdown of triglycerides that are stored in the muscle. For
complete oxidation of these sources of energy, the metabolic intermediate
acetyl coenzyme A (acetyl-CoA) must be oxidized through the TCA cycle,
and the reducing equivalents produced (NADH and FADH2) must be trans-
ferred to O2 through the mitochondrial electron transport system. This electron
transfer process produces a proton gradient across the inner mitochondrial
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