Lipid Metabolism, Ketogenesis, and Fatty Acid Oxidation

Vocabulary practice flashcards covering lipid digestion and absorption, adipose tissue dynamics, fatty acid oxidation pathways, and the synthesis, regulation, and breakdown of ketone bodies.

Ketone Bodies

A group of three water-soluble compounds—acetoacetate, $D\text{-}\beta\text{-hydroxybutyrate}$, and acetone—synthesized in the liver mitochondrial matrix from acetyl-CoA.

Ketogenesis

The biochemical pathway occurring in the mitochondrial matrix of liver cells that converts acetyl-CoA derived from fatty acid oxidation and ketogenic amino acids into ketone bodies.

Ketolysis

The breakdown of ketone bodies into acetyl-CoA within extrahepatic mitochondria, which enters the TCA cycle to yield $CO_2$, $H_2O$, and ATP; this process spares glucose oxidation in the brain during starvation.

$$\beta\text{-Ketoacyl-CoA Transferase}$$

An extrahepatic mitochondrial enzyme (also known as thiophorase) that transfers a CoA moiety from succinyl-CoA to acetoacetate, generating acetoacetyl-CoA; its absence in the liver prevents the liver from consuming its own ketone bodies.

Ketosis

A metabolic state defined by the concurrent presence of ketonemia (blood ketone level exceeding the normal threshold of $< 3\text{ mg/dl}$) and ketonuria (urine ketone level exceeding $< 40\text{ mg/dl}$).

Diabetic Ketoacidosis (DKA)

A severe metabolic acidosis triggered by high ketone body accumulation; urinary excretion of ketone bodies depletes buffer cations ($Na^+$, $K^+$, and $NH_4^+$), driving a decrease in blood bicarbonate ($HCO_3^-$).

Symptoms of Ketoacidosis

Clinical features resulting from systemic ketone body accumulation and acid-base disruption, which include abdominal pain, nausea, vomiting, pear-drop acetone breath odor, deep heavy breathing, muscular pain, and apathy.

Ketogenic Compounds

Substances that enhance or activate ketogenesis and lipolysis, including dietary fats, free fatty acids, ketogenic amino acids, glucagon, epinephrine, and growth hormone.

Anti-Ketogenic Compounds

Substances that suppress ketogenesis and promote lipogenesis or esterification, including carbohydrates, proteins, glycerol, and insulin.

Lingual Lipase

A digestive enzyme secreted by Ebner's glands on the dorsal surface of the tongue; its contribution to triacylglycerol digestion is minimal because food resides in the oral cavity for only a short period.

Gastric Lipase

An acid-sensitive lipase with an optimum pH of 7 that is ineffective in the adult stomach (pH $1\text{–}2$), but functions in the infant stomach (pH 5) to digest milk fats.

Pancreatic Lipase

The primary digestive enzyme for triacylglycerols, which cleaves the primary ester bonds at carbons 1 and 3 to yield free fatty acids and $2\text{-monoacylglycerols}$.

Steatorrhea

An abnormal rise in fecal fat excretion resulting from impaired lipid digestion or absorption, caused by deficiencies in pancreatic lipase or bile salts, or defects in intestinal mucosal cells.

Phospholipases

A class of esterases hydrolyzing phospholipids: phospholipase $A_1$ cleaves the position-1 acyl chain, phospholipase $A_2$ removes the position-2 fatty acid to yield a lysophospholipid, phospholipase C cleaves the glycerol-phosphate bond, and phospholipase D removes the nitrogenous or polar head group.

Chylomicrons

Lipoprotein assemblies generated within intestinal mucosal cells containing resynthesized triacylglycerols, phospholipids, cholesterol, and apolipoprotein $B_{48}$, which travel through lacteals and the thoracic duct into systemic circulation.

Tissue Fat

Structural lipids consisting mainly of phospholipids and cholesteryl esters located in cell walls and the brain; their quantities remain constant and do not decline during starvation.

Depot Fat

Storage lipids predominantly made of triacylglycerols rich in saturated fatty acids located under the skin and around the kidneys; their reserves are variable and decrease during starvation to yield energy ($9.3\text{ kcal/g}$).

Lipogenesis

The anabolic pathway in which fatty acids and triacylglycerols are synthesized from excess carbohydrates, stimulated postprandially by elevated insulin.

Glycerol Kinase Deficiency in Adipocytes

The absence of the enzyme glycerol kinase in adipose tissue and muscle, forcing adipocytes to utilize glycolytic dihydroxyacetone phosphate (DHAP) rather than free glycerol to form glycerol-3-phosphate for triacylglycerol synthesis.

Hormone-Sensitive Triacylglycerol Lipase

The rate-limiting enzyme in adipose tissue lipolysis that initiates triacylglycerol hydrolysis; its activity is upregulated by epinephrine, cortisol, and glucagon, and downregulated by insulin.

$$\beta\text{-Oxidation}$$

A repetitive mitochondrial pathway in the liver, kidney, and heart that cleaves two-carbon acetyl-CoA units sequentially from the carboxyl end of fatty acyl-CoA, producing one $FADH_2$ and one $NADH$ per cycle.

Net ATP Yield of Palmitic Acid

The net energy generated from completely oxidizing palmitic acid ($16\text{ C}$), evaluated by $[(N/2 - 1) \times 5\text{ ATP}] + [(N/2) \times 12\text{ ATP}] - 2\text{ ATP}$, resulting in $35 + 96 - 2 = 129\text{ ATP}$.

$$\alpha\text{-Oxidation}$$

A peroxisomal pathway primarily functioning in the brain and nervous tissue that removes one carbon at a time from the $\alpha\text{-position}$ of $\beta\text{-methylated}$ fatty acids without utilizing coenzyme A or generating ATP.

Phytanic Acid

A branched-chain fatty acid ($3,7,11,15\text{-tetramethyl palmitic acid}$) derived from plant sources and animal fats whose $\beta\text{-methyl}$ group prevents direct entry into $\beta\text{-oxidation}$, requiring initial peroxisomal $\alpha\text{-oxidation}$.

Refsum's Disease

An autosomal recessive metabolic defect characterized by a deficiency in peroxisomal $\alpha\text{-oxidation}$, causing phytanic acid to accumulate in nervous tissues and leading to polyneuropathy, cerebellar ataxia, deafness, and blindness.

$$\omega\text{-Oxidation}$$

A specialized oxidation pathway that targets the terminal methyl ($\text{–}CH_3$) group of fatty acids, producing dicarboxylic acids ($HOOC\text{-}R\text{-}COOH$) utilized in brain cell membrane structure.

Acetyl-CoA

A central metabolic intersection produced from carbohydrates, triglycerides, and ketogenic amino acids that provides carbon units for the TCA cycle, ketogenesis, fatty acid synthesis, steroidogenesis, and acetylation reactions.