Fatty Acid and Protein Metabolism (1D) - MCAT Biological and Biochemical Foundations of Living Systems

Free NH$_3$ (carbamoyl phosphate) and aspartate. The urea cycle incorporates ammonia into carbamoyl phosphate and nitrogen from aspartate to eliminate excess nitrogen as urea.

Thiolysis by thiolase; requires CoA-SH. Thiolase performs CoA-dependent thiolysis to cleave beta-ketoacyl-CoA into acetyl-CoA and a shortened acyl-CoA in the final beta-oxidation step.

Acyl-CoA dehydrogenase. Acyl-CoA dehydrogenase catalyzes the initial dehydrogenation in beta-oxidation, forming a trans double bond and reducing FAD to FADH$_2$.

106 ATP (using $2.5$ per NADH and $1.5$ per FADH$_2$). Palmitate oxidation yields 106 ATP accounting for reduced cofactors at 2.5 ATP per NADH and 1.5 per FADH$_2$, minus activation cost.

$\frac{n}{2} - 1$ cycles. Complete beta-oxidation of an even-chain fatty acid requires cycles equal to half the carbon number minus one to yield acetyl-CoA units.

Acetyl-CoA + FADH$_2$ + NADH + shortened acyl-CoA. Each beta-oxidation cycle cleaves two carbons as acetyl-CoA while generating reduced cofactors and a fatty acyl-CoA shortened by two carbons.

Oxidation (FAD), hydration, oxidation (NAD$^+$), thiolysis. Beta-oxidation cycles sequentially remove two-carbon units through FAD-dependent oxidation, water addition, NAD$^+$-dependent oxidation, and CoA-mediated cleavage.

Malonyl-CoA. Malonyl-CoA, produced during fatty acid synthesis, allosterically inhibits CPT I to avoid simultaneous synthesis and degradation in mitochondria.

Carnitine shuttle (CPT I, translocase, CPT II). The carnitine shuttle facilitates transport of long-chain acyl groups across the mitochondrial membrane via CPT I conjugation, translocase movement, and CPT II reformation.

Fatty acyl-CoA (ATP is converted to AMP + PPi). Acyl-CoA synthetase activates fatty acids by forming thioester bonds with CoA, hydrolyzing ATP to AMP and PPi for energy.

Beta-hydroxybutyrate (a hydroxy acid, not a ketone). Beta-hydroxybutyrate arises from NADH reduction of acetoacetate, classifying it as a hydroxy acid rather than a true ketone structure.

Acetone. Acetone forms via non-enzymatic decarboxylation of acetoacetate, contributing to the fruity breath odor in uncontrolled diabetic ketoacidosis.

HMG-CoA synthase; forms HMG-CoA. HMG-CoA synthase condenses acetoacetyl-CoA with acetyl-CoA to form HMG-CoA, controlling the rate of ketogenesis in liver mitochondria.

Liver. The liver produces ketone bodies but lacks the transferase enzyme needed to convert them back to acetyl-CoA for energy use.

Glutamine. Glutamine safely transports ammonia by incorporating it into its amide group, preventing toxicity during delivery to the liver for urea synthesis.

Alanine. Alanine transfers amino groups from muscle amino acid breakdown to the liver, where transamination regenerates pyruvate for gluconeogenesis.

Pyridoxal phosphate (PLP, vitamin B$_6$). Pyridoxal phosphate acts as a cofactor in transamination reactions, facilitating amino group transfer between amino acids and alpha-keto acids.

Glutamate dehydrogenase. Glutamate dehydrogenase catalyzes NAD(P)$^+$-dependent oxidative deamination of glutamate, liberating ammonia for urea cycle entry in liver mitochondria.

Water-soluble $4$-carbon fuels; used by brain (fasting) and muscle. Ketone bodies serve as soluble four-carbon energy sources derived from acetyl-CoA, primarily utilized by brain during fasting and by muscle.

Peroxisomal $\beta$-oxidation (acyl-CoA oxidase forms $H_2O_2$). Peroxisomal beta-oxidation shortens very long chains, with acyl-CoA oxidase directly producing H$_2$O$_2$ instead of FADH$_2$ for energy conservation.

Biotin then B${12}$ (methylmalonyl-CoA mutase step). Propionyl-CoA carboxylase (biotin) forms methylmalonyl-CoA, which methylmalonyl-CoA mutase (B${12}$) rearranges to succinyl-CoA for TCA cycle entry.

Propionyl-CoA + acetyl-CoA (from the final cleavage). Odd-chain fatty acids undergo beta-oxidation until the final thiolysis yields propionyl-CoA and acetyl-CoA from the remaining five-carbon chain.

2,4-Dienoyl-CoA reductase (uses NADPH). 2,4-Dienoyl-CoA reductase reduces conjugated double bonds using NADPH, enabling isomerase and hydratase to process polyunsaturated chains in beta-oxidation.

Enoyl-CoA isomerase. Enoyl-CoA isomerase repositions cis double bonds to trans configuration, allowing subsequent hydration and continuation of the beta-oxidation pathway.