fatty acid
Summary
Fatty acids are long hydrocarbon chains with a terminal carboxyl group that serve as key energy substrates, membrane components, and signaling molecules. They are classified as saturated (no double bonds) or unsaturated (one or more double bonds), and their oxidation (beta-oxidation) generates large amounts of ATP, especially important during fasting states.
Detail
Fatty acids are carboxylic acids with long aliphatic tails (typically 4-28 carbons), classified by chain length (short, medium, long, very long) and saturation (saturated vs mono/polyunsaturated). They are stored as triglycerides in adipose tissue and released via hormone-sensitive lipase during fasting (stimulated by glucagon, epinephrine, cortisol; inhibited by insulin). Free fatty acids bound to albumin travel to tissues, where they undergo beta-oxidation in mitochondria after activation to acyl-CoA and transport via the carnitine shuttle (rate-limiting enzyme: carnitine palmitoyltransferase I, inhibited by malonyl-CoA during fed state). Beta-oxidation produces acetyl-CoA, NADH, and FADH2, feeding into the TCA cycle and oxidative phosphorylation; in the liver, excess acetyl-CoA is converted to ketone bodies during prolonged fasting or diabetic ketoacidosis. Essential fatty acids (linoleic acid, alpha-linolenic acid) cannot be synthesized by humans and are precursors for eicosanoids (prostaglandins, thromboxanes, leukotrienes) via arachidonic acid metabolism. Clinically relevant conditions include: medium-chain acyl-CoA dehydrogenase (MCAD) deficiency causing hypoketotic hypoglycemia and vomiting during fasting; carnitine deficiency/CPT deficiency impairing long-chain fatty acid oxidation; and elevated free fatty acids contributing to insulin resistance in metabolic syndrome. Fatty acid synthesis occurs in the cytoplasm using acetyl-CoA carboxylase (rate-limiting, activated by citrate and insulin, inhibited by glucagon and palmitoyl-CoA) and fatty acid synthase, primarily in liver and adipose tissue during the fed state.
Sources
- First Aid for the USMLE Step 1
- Lippincott Illustrated Reviews: Biochemistry
- Harper's Illustrated Biochemistry
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