Fatty Acid-Binding Protein 3 (FABP3) is a protein that functions like a cellular taxi service for fatty acids, binding with these molecules and transporting them where they are needed inside a cell. Due to its high concentration and activity in the heart muscle, it is more commonly known as Heart-type Fatty Acid-Binding Protein (H-FABP). This protein is part of a larger family of similar fatty acid-binding proteins, each with a specialized role in different tissues.
Cellular Function and Location
The primary function of FABP3 is to manage the movement of long-chain fatty acids within the cytoplasm, the watery interior of a cell. Once fatty acids pass through the cell membrane, they cannot easily travel through this aqueous environment. FABP3 addresses this by binding to the fatty acids, shielding them for transport to the mitochondria. The mitochondria act as the cell’s power plants, converting these fatty acids into energy through a process called β-oxidation.
This transport system is active in tissues with high energy demands, primarily the heart muscle (myocardium) and skeletal muscles. These tissues rely on fatty acid metabolism to fuel their continuous work. The abundance of FABP3 in these cells, where it can make up 5-15% of the total protein in the cytoplasm, reflects their dependence on this energy supply. Without this protein shuttle, fuel delivery would be compromised.
FABP3 is a small protein, with a molecular weight of about 15 kilodaltons (kDa), which allows it to move swiftly within the cell. Its structure forms a clam-like shell or “beta-barrel” that creates an internal cavity. This cavity is where a single fatty acid molecule is held during transport. This design ensures the fatty acid is securely transported to the mitochondria or the nucleus, where it can also be involved in modulating gene expression.
Role in Cardiac Health and Disease
The heart has an immense need for energy, deriving approximately 70% of it from the breakdown of fatty acids. This makes the efficient transport of fatty acids by FABP3 a fundamental process for normal cardiac function. A steady supply of this fuel is necessary to maintain the heart’s mechanical and electrical activities.
This reliance on fatty acids also means the heart is vulnerable when that supply chain is disrupted. During a myocardial infarction (heart attack), a blockage in a coronary artery cuts off oxygen-rich blood flow to a section of the heart muscle. This lack of oxygen, or ischemia, leads to injury and death of the heart muscle cells (cardiomyocytes). When these cells are damaged, their outer membranes rupture.
Because FABP3 is small and abundant within cardiomyocytes, it is one of the first proteins to be released from the damaged cells into the bloodstream. The appearance of FABP3 in the blood is a direct consequence of myocardial injury. This rapid leakage forms the basis for its use in a clinical setting.
Clinical Significance as a Biomarker
In medicine, a biomarker is a substance measured to provide information about a disease. FABP3 has gained attention as a biomarker for acute myocardial infarction because it is released into the circulation when heart muscle cells are injured. Its advantage is the speed at which this occurs, as detectable levels can appear in a patient’s blood within one to three hours after the onset of chest pain.
This rapid release provides an early window for diagnosis compared to troponin, a common biomarker that begins to rise in the blood two to four hours after the event. Its levels in the blood usually peak around four to six hours after the injury and return to normal within about 20 hours.
While FABP3 is a sensitive early marker, it is not as specific to the heart as troponin. Troponin is a protein more exclusively found in heart muscle, whereas FABP3 is also present in skeletal muscle. For this reason, a high FABP3 level indicates muscle damage, but not definitively from the heart. Clinicians often use FABP3 measurements in combination with troponin tests, leveraging the speed of FABP3 for early detection and the specificity of troponin for confirmation.
Connection to Other Health Conditions
Although best known for its role in cardiac health, FABP3’s appearance in the bloodstream can signal other health issues. Since FABP3 is abundant in skeletal muscle, conditions that cause significant muscle damage can also lead to elevated levels. Research has linked circulating FABP3 levels to a broader range of conditions beyond acute muscle injury, including:
- Severe injuries from trauma or extreme exercise
- Rhabdomyolysis, a condition where skeletal muscle breaks down rapidly
- Metabolic syndrome, a cluster of conditions that increase the risk of heart disease and diabetes
- Chronic kidney disease
- Peripheral artery disease
These connections suggest that while its primary clinical use is in cardiology, FABP3 may offer insights into systemic health.