CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 27: M Y O C A R D IA L IN FA R C T IO N
A 51-year-old male with a history of chest pain with exertion pres-
ents with retrosternal chest pressure that radiates to the neck. He has nausea
and diaphoresis while at rest. The patient has ST segment elevation and peaked
T waves in the inferior ECG leads. The troponin I and T levels are elevated.
Likely diagnosis: Acute myocardial infarction.
Biochemical shuttle: The malate-aspartate shuttle is primarily seen in
the heart, liver, and kidney. This shuttle requires cytosolic and
mitochondrial forms of malate dehydrogenase and glutamate-oxaloacetate
transaminase and two antiporters, the malate-a-ketoglutarate antiporter
and the glutamate-aspartate antiporter, which are both localized in the
mitochondrial inner membrane. In this shuttle cytosolic nicotinamide
adenine dinucleotide (NADH) is oxidized to regenerate cytosolic NAD+
by reducing oxaloacetate to malate by cytosolic malate dehydrogenase.
C L IN IC A L C O R R E L A T IO N
The most common cause of death of Americans is coronary heart disease. The
patient’s symptoms in this case are very typical of myocardial infarction, that is,
chest pressure or chest pain, often radiating to the neck or to the left arm. The
pain is usually described as deep and “squeezing chest pain.” Cardiac muscle
is perfused by coronary arteries with very little redundant or shared circula-
tion; thus, occlusion of one coronary artery usually leads to ischemia or necro-
sis of the corresponding cardiac muscle. Laboratory confirmation of
myocardial infarction (death of cardiac muscle) includes ECG showing eleva-
tion of the ST segment and/or increase of the cardiac enzymes. When there is
insufficient oxygen available for the cardiac muscle, then the glycolytic path-
way must be used, which leads to a very small amount of ATP per glucose
molecule. The malate-aspartate shuttle can offer two or three more times the
ATP by oxidizing NADH to regenerate cytosolic NAD+ by reducing oxaloac-
etate to malate by cytosolic malate dehydrogenase.
A PPR O A C H TO G L Y C O LY SIS A N D T H E
M A LA TE-A SPA R TA TE SH U T T L E
Be familiar with glycolysis.
Know the role of glycerol 3-phosphate and the malate-aspartate shuttle.
Be aware of the role of mitochondria in glycolysis.