Myocardial Infarction Case File

https://medical-phd.blogspot.com/2021/03/myocardial-infarction-case-file.html

Eugene C.Toy, MD, William E. Seifert, Jr., PHD, Henry W. Strobel, PHD, Konrad P. Harms, MD

❖ CASE 27
A 51-year-old male presents to the emergency center with chest pain. He states that he has had
chest discomfort or pressure intermittently over the last year especially with increased activity. He
describes the chest pain as a pressure behind his breastbone that spreads to the left side of his neck.
Unlike previous episodes, he was lying down, watching television. The chest pain lasted
approximately 15 minutes then subsided on its own. He also noticed that he was nauseated and
sweating during the pain episode. He has no medical problems that he is aware of and has not been
to a physician for several years. On examination, he is in no acute distress with normal vital signs.
His lungs were clear to auscultation bilaterally, and his heart had a regular rate and rhythm with no
murmurs. An electrocardiogram (ECG) revealed ST segment elevation and peaked T waves in
leads II, III, and aVF. Serum troponin I and T levels are elevated.

◆ What is the most likely diagnosis?

◆ What biochemical shuttle may be active to produce more adenosine triphosphate (ATP) per
glucose molecule?

ANSWERS TO CASE 27: MYOCARDIAL INFARCTION

Summary: A 51-year-old male with a history of chest pain with exertion presents 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-α-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.

CLINICAL CORRELATION
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
circulation; thus, occlusion of one coronary artery usually leads to ischemia or necrosis of the
corresponding cardiac muscle. Laboratory confirmation of myocardial infarction (death of cardiac
muscle) includes ECG showing elevation of the ST segment and/or increase of the cardiac
enzymes. When there is insufficient oxygen available for the cardiac muscle, then the glycolytic
pathway 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 oxaloacetate to malate by cytosolic malate dehydrogenase.

APPROACH TO GLYCOLYSIS AND THE MALATE-ASPARTATE SHUTTLE

Objectives
1. Be familiar with glycolysis.
2. Know the role of glycerol 3-phosphate and the malate-aspartate shuttle.
3. Be aware of the role of mitochondria in glycolysis.

Definitions

Myocardial infarction: An area of heart muscle is inadequately perfused as a result of cardiac

vessel occlusion resulting in ischemia, cell death, and loss of cell constituents including enzymes
into the circulation. Electrocardiographic changes occur as a result of damaged heart tissue.

Angina: Transient disruption of adequate blood flow to a portion of heart muscle leading to pain
and a temporary shift to anaerobic glycolysis producing pyruvate and lactate that are released into
the circulation.

Aerobic glycolysis: Metabolism of glucose to pyruvate. Pyruvate in the presence of sufficient

oxygen can be metabolized to CO2 via the tricarboxylic acid cycle in the mitochondrion-producing
NADH and FADH2, which contribute elections through the electron transfer chain to molecular
oxygen producing H2O and ATP.

Anaerobic glycolysis: Metabolism of glucose to lactate in the absence of sufficient oxygen. When

oxygen is lacking, pyruvate is converted to lactate, and no further oxidative pathway is available.

Electron shuttles: Enzymatic processes whereby electrons from NADH can be transferred across
the mitochondrial barrier. The glycerol 3-phosphate shuttle uses the reduction of
dihydroxyacetone phosphate to glycerol 3-phosphate and reoxidation to transfer electrons from
cytosolic NADH to coenzyme Q in the electron transport chain. The malateaspartate shuttle uses
malate and aspartate in a two-member transfer exchange to transfer electrons from cytosolic NADH
to mitochondrial NADH (see Figures 27-2 and 27-3).