Fatty Acid and Protein Metabolism (1D) - Bio & Biochem

1. What is the key additional enzyme needed for polyunsaturated fatty acid oxidation beyond isomerase?

   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.

2. Which shuttle transports long-chain fatty acyl groups into the mitochondrial matrix for $\beta$-oxidation?

   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.

3. Which ketone body is not a true ketone, and what is its name?

   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.

4. Which enzyme introduces a double bond during the first oxidation step of $\beta$-oxidation?

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

5. Identify the net ATP yield commonly used on MCAT for complete oxidation of palmitate ($C_{16}$).

   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.

6. What is the defining feature of ketone bodies regarding carbon content and typical tissues that use them?

   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.

7. Which enzyme releases free ammonia from glutamate during oxidative deamination in the liver mitochondria?

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

8. What is the final cleavage step of $\beta$-oxidation called, and what cofactor is required?

   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.

9. What is the key cofactor required by aminotransferases (transaminases) in amino acid catabolism?

   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.

10. What cofactor-dependent sequence converts propionyl-CoA to succinyl-CoA in odd-chain FA metabolism?

    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.

11. What are the direct products of one $\beta$-oxidation cycle of a saturated fatty acyl-CoA?

    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.

12. State the number of acetyl-CoA molecules produced from a saturated even-chain fatty acid with $n$ carbons.

    $\frac{n}{2}$ acetyl-CoA. Beta-oxidation of even-chain fatty acids produces acetyl-CoA molecules equal to half the original carbon count through sequential two-carbon cleavages.

13. What are the two nitrogen sources that enter the urea cycle to form urea?

    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.

14. Which ketone body is spontaneously formed from acetoacetate and is exhaled in ketoacidosis?

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

15. What are the final products of odd-chain fatty acid $\beta$-oxidation after the last cycle?

    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.

16. Which enzyme is required to continue $\beta$-oxidation past a cis double bond in an unsaturated fatty acid?

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

17. What is the nitrogen carrier that transports ammonia safely from most tissues to the liver?

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

18. State the number of $\beta$-oxidation cycles required for a saturated even-chain fatty acid with $n$ carbons.

    $\frac{n}{2} - 1$ 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.

19. Which tissue cannot use ketone bodies because it lacks thiophorase (succinyl-CoA:acetoacetate CoA transferase)?

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

20. What molecule inhibits CPT I to prevent mitochondrial fatty acid entry during fatty acid synthesis?

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

21. What are the four recurring reaction types in one cycle of mitochondrial $\beta$-oxidation?

    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.

22. Which pathway uses fatty acids in peroxisomes and produces $H_2O_2$ instead of FADH$_2$ for the ETC?

    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.

23. What is the immediate product formed when a fatty acyl-CoA is activated by acyl-CoA synthetase?

    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.

24. Which liver enzyme is rate-limiting for ketogenesis and what molecule does it produce first?

    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.

25. Which molecule carries amino nitrogen from muscle to liver in the glucose-alanine cycle?

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

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