Question 1

Inborn Error of Metabolism—Dietary Advice in Phenylketonuria (PKU) A person diagnosed with phenylketonuria (PKU) is advised to avoid which of the following products due to its phenylalanine content?

Accepted Answer

Introduction / Context: Phenylketonuria (PKU) is an inherited deficiency of phenylalanine hydroxylase (or related cofactor pathways), leading to accumulation of phenylalanine and potentially neurotoxic metabolites. Dietary management centers on limiting phenylalanine intake to prevent cognitive impairment and other complications. Given Data / Assumptions: PKU patients require lifelong control of phenylalanine intake. Aspartame is a dipeptide methyl ester composed of aspartate and phenylalanine. Common foods vary widely in phenylalanine content. Concept / Approach: Any source rich in phenylalanine should be restricted. Aspartame, used in many “diet” beverages and sugar-free products, releases phenylalanine upon digestion and therefore must be avoided or carefully monitored in PKU. Carbohydrates like glucose do not directly contribute phenylalanine. Non-essential amino acids (e.g., glycine) and general fats are unrelated to phenylalanine load, though overall diet must still be balanced. Step-by-Step Solution: Identify the metabolic block: impaired conversion of phenylalanine to tyrosine.Recognize aspartame composition: L-aspartyl-L-phenylalanine methyl ester.Conclude that ingesting aspartame increases phenylalanine burden.Therefore, select aspartame as the product to avoid. Verification / Alternative check: Food labels in many countries carry warnings: “Phenylketonurics: contains phenylalanine,” especially on products sweetened with aspartame. Why Other Options Are Wrong: Glycine-containing foods: glycine is not phenylalanine. High-fat foods: unrelated to phenylalanine content per se. Glucose/fructose: carbohydrates lacking amino acids. Common Pitfalls: Overlooking hidden sources of aspartame in beverages, chewing gums, and medications; confusing phenylalanine with other amino acids. Final Answer: Aspartame (artificial sweetener)

Question 2

Amino Acid Catabolism—Definition of a Ketogenic Amino Acid A “ketogenic” amino acid is defined as one that degrades to which end-product(s)?

Accepted Answer

Introduction / Context: Amino acids are classified as glucogenic, ketogenic, or both based on the metabolic fate of their carbon skeletons. This classification predicts whether they can contribute to net glucose synthesis or ketone body formation, which is central to understanding fasting metabolism and certain inborn errors. Given Data / Assumptions: Glucogenic amino acids yield pyruvate or TCA intermediates that can form oxaloacetate and, ultimately, glucose. Ketogenic amino acids yield acetyl-CoA or acetoacetyl-CoA, precursors for ketone bodies and fatty acid synthesis. Some amino acids are both glucogenic and ketogenic. Concept / Approach: “Ketogenic” specifically denotes degradation to acetyl-CoA or acetoacetyl-CoA, which cannot produce net glucose because the two-carbon acetyl unit is lost as CO2 in the TCA cycle. Classic purely ketogenic amino acids are leucine and lysine; several others are mixed (e.g., isoleucine, phenylalanine, tryptophan, tyrosine). Step-by-Step Solution: Define categories: glucogenic vs ketogenic vs both.Match “ketogenic” with acetyl-CoA or acetoacetyl-CoA production.Exclude options that yield pyruvate/TCA intermediates as primarily glucogenic.Select the precise definition: acetyl-CoA or acetoacetyl-CoA. Verification / Alternative check: Biochemistry texts list leucine/lysine as exclusively ketogenic, confirming the definition anchored in acetyl-CoA/acetoacetyl-CoA outcomes. Why Other Options Are Wrong: Keto-sugars: a carbohydrate term, not a metabolic fate of amino acids. Pyruvate/TCA intermediates: describe glucogenic fates. “Multiple intermediates…”: describes “both” category, not strictly ketogenic. Only succinyl-CoA: one TCA intermediate (glucogenic via OAA), not ketogenic. Common Pitfalls: Assuming acetyl-CoA can become glucose; net glucose cannot be formed from pure acetyl units in animals. Final Answer: Either acetyl-CoA or acetoacetyl-CoA

Question 3

Amino Group Transfer—Recognizing a Transamination Reaction Which of the following equations correctly represents a transamination process mediated by an aminotransferase?

Accepted Answer

Introduction / Context: Transamination reactions transfer an amino group from an amino acid to an α-keto acid, forming a new amino acid and a new α-keto acid. They are central to nitrogen metabolism, funneling amino groups toward glutamate and linking amino acid catabolism with the TCA cycle carbon skeletons. Given Data / Assumptions: Aminotransferases require pyridoxal phosphate (PLP) as a cofactor. Common pairs include alanine/pyruvate and aspartate/oxaloacetate, with α-ketoglutarate/glutamate as the principal amino/keto pair. Reactions are reversible and do not release free ammonia. Concept / Approach: A hallmark example is aspartate aminotransferase: aspartate + α-ketoglutarate ⇄ oxaloacetate + glutamate. This swaps the amino group from aspartate to α-ketoglutarate, generating glutamate and the corresponding keto acid (oxaloacetate). Reactions that release NH3 are deamination, not transamination, and fatty acids do not participate in aminotransferase chemistry. Step-by-Step Solution: Identify the amino donor (aspartate) and acceptor (α-ketoglutarate).Predict products: oxaloacetate (keto form of aspartate) and glutamate (amino form of α-ketoglutarate).Confirm no free ammonia is released—consistent with transamination.Select the balanced reversible equation for transamination. Verification / Alternative check: Clinical assays of AST (aspartate aminotransferase) rely on this exact reaction, underscoring its physiological relevance. Why Other Options Are Wrong: Options a/d: depict deamination with NH3 release, not transamination. Option b: includes a fatty acid (hexanoic acid), not a typical α-keto acid partner. Option e: alanine → acetyl-CoA is not a transamination and incorrectly releases NH3. Common Pitfalls: Confusing transamination (no free NH3) with oxidative deamination (generates NH3) and including non-keto acids like fatty acids as substrates. Final Answer: Aspartate + α-ketoglutarate ⇄ glutamate + oxaloacetate

Question 4

Amino Acid Classification—Fate of Histidine Carbon Skeleton Histidine is catabolized to α-ketoglutarate. Based on this metabolic fate, how is histidine classified?

Accepted Answer

Introduction / Context: Amino acids are labeled glucogenic if their carbon skeletons can be converted into glucose precursors (e.g., pyruvate or TCA intermediates), and ketogenic if they form acetyl-CoA or acetoacetyl-CoA, fueling ketone body synthesis. Correctly classifying amino acids is fundamental to understanding fasting metabolism and dietary management in metabolic disorders. Given Data / Assumptions: Histidine degrades to α-ketoglutarate. α-Ketoglutarate is a TCA cycle intermediate. TCA intermediates can generate oxaloacetate and thereby contribute to gluconeogenesis. Concept / Approach: Because α-ketoglutarate can be converted to oxaloacetate and then to phosphoenolpyruvate and glucose, any amino acid whose catabolism yields α-ketoglutarate is glucogenic. Only amino acids yielding acetyl-CoA or acetoacetyl-CoA without producing gluconeogenic intermediates are purely ketogenic (e.g., leucine and lysine). Some amino acids are both, but histidine is classically glucogenic via α-ketoglutarate. Step-by-Step Solution: Note the endpoint of histidine catabolism: α-ketoglutarate.Map α-ketoglutarate → oxaloacetate through TCA reactions.Oxaloacetate can feed gluconeogenesis → glucose formation.Therefore, classify histidine as glucogenic. Verification / Alternative check: Standard biochemical tables list histidine among glucogenic amino acids, consistent with its entry into the TCA cycle at α-ketoglutarate. Why Other Options Are Wrong: Ketogenic: would require degradation to acetyl-CoA/acetoacetyl-CoA. Both: histidine does not significativamente yield acetyl-CoA as an exclusive fate. “Gluco amino acid”: non-standard terminology; correct term is glucogenic. Neither: contradicted by its clear glucogenic pathway. Common Pitfalls: Assuming all amino acids can become both glucose and ketone bodies; only a subset is mixed. Terminology should be precise. Final Answer: Glucogenic amino acid

Question 5

Amino acid metabolism (classification): Which of the following is the best example of a glucogenic amino acid in human metabolism?

Accepted Answer

Introduction / Context: In biochemistry, amino acids are categorized as glucogenic, ketogenic, or both, based on the fate of their carbon skeletons after deamination. A glucogenic amino acid can yield intermediates that become glucose via gluconeogenesis. This classification is crucial for understanding fasting metabolism, inborn errors, and dietary planning in metabolic disorders. Given Data / Assumptions: Lysine and leucine are considered purely ketogenic in standard textbooks. Valine is a branched-chain amino acid that is purely glucogenic. Tryptophan is both glucogenic and ketogenic (dual fate). Concept / Approach: Identify which option yields carbon skeletons that become pyruvate or tricarboxylic acid (TCA) cycle intermediates (such as oxaloacetate, fumarate, succinyl-CoA, or alpha-ketoglutarate) that feed gluconeogenesis. Valine is catabolized to propionyl-CoA and then to succinyl-CoA, a TCA intermediate, making it classically glucogenic. By contrast, lysine and leucine produce acetyl-CoA or acetoacetyl-CoA and cannot yield net glucose in humans, so they are ketogenic. Tryptophan produces both glucogenic and ketogenic products, so it is not the best single example of purely glucogenic behavior. Step-by-Step Solution: Determine each amino acid's end products after deamination and pathway steps.Note that valine → propionyl-CoA → methylmalonyl-CoA → succinyl-CoA (glucogenic).Recognize lysine/leucine → acetyl-CoA/acetoacetyl-CoA (ketogenic).Recall tryptophan has mixed products; not purely glucogenic. Verification / Alternative check: Clinical nutrition texts list valine, isoleucine (partial), and methionine as contributors to succinyl-CoA; lysine and leucine are explicitly labeled ketogenic. This scheme aligns with standard metabolic maps used in medical biochemistry courses. Why Other Options Are Wrong: Lysine: strictly ketogenic; does not yield net glucose. Tryptophan: both glucogenic and ketogenic; not the best exclusively glucogenic example. Leucine: strictly ketogenic. None of these: incorrect because valine is a clear glucogenic amino acid. Common Pitfalls: Confusing the dual-fate amino acids (e.g., isoleucine, phenylalanine, tryptophan, tyrosine) with purely glucogenic or purely ketogenic ones; also assuming all branched-chain amino acids behave identically. Final Answer: Valine

Question 6

Definition checkpoint: A glucogenic amino acid is one whose carbon skeleton is ultimately degraded to which class of metabolic products?

Accepted Answer

Introduction / Context: Glucogenic amino acids are those that can serve as precursors for gluconeogenesis. After transamination or deamination, their carbon skeletons enter central metabolism as compounds that the liver can use to synthesize glucose, especially during fasting or prolonged exercise. Understanding this definition is foundational for physiology and clinical biochemistry. Given Data / Assumptions: Gluconeogenesis requires substrates that can be converted to oxaloacetate and then to phosphoenolpyruvate. Pyruvate and TCA cycle intermediates (e.g., oxaloacetate, fumarate, succinyl-CoA, alpha-ketoglutarate) are direct entry points to glucose formation. Acetyl-CoA and acetoacetyl-CoA carbons cannot produce net glucose in humans. Concept / Approach: Relate the endpoint of amino acid carbon skeletons to gluconeogenic capacity. If the endpoint is pyruvate or a TCA intermediate that can yield oxaloacetate, the amino acid is glucogenic. If the endpoint is acetyl-CoA or acetoacetyl-CoA (which lose carbons as CO2 in the TCA cycle), the amino acid is ketogenic. Lipid-related endpoints do not directly re-enter gluconeogenesis in humans for net glucose production. Step-by-Step Solution: Identify the relevant gluconeogenic nodes: pyruvate and TCA intermediates.Map amino acid catabolic products to these nodes.Exclude acetyl-CoA/acetoacetyl-CoA endpoints as non-glucogenic.Choose the option that explicitly states pyruvate or TCA intermediates. Verification / Alternative check: Standard metabolic charts group amino acids by their ability to produce pyruvate, oxaloacetate, fumarate, succinyl-CoA, or alpha-ketoglutarate (glucogenic) versus those that produce acetyl-CoA or acetoacetyl-CoA (ketogenic). Why Other Options Are Wrong: Keto-sugars: not a standard endpoint of amino acid catabolism. Acetyl-CoA/acetoacetyl-CoA: defines ketogenic, not glucogenic, fate. Long-chain fatty acyl-CoA: belongs to fatty acid metabolism, not direct gluconeogenesis. None of the above: incorrect because the correct definition is provided. Common Pitfalls: Assuming acetyl-CoA can be converted back to glucose in animals; the pyruvate dehydrogenase step is irreversible, preventing net glucose production from even-chain fatty acids or purely ketogenic amino acids. Final Answer: Pyruvate or tricarboxylic acid (TCA) cycle intermediates

Question 7

Amino acid metabolism (classification): Which option below is the best-described purely ketogenic amino acid in humans?

Accepted Answer

Introduction / Context: Amino acids are termed ketogenic if their carbon skeletons are degraded exclusively to acetyl-CoA or acetoacetyl-CoA, yielding ketone bodies or entering fatty acid synthesis, but not producing net glucose. Only a few are purely ketogenic. Identifying them is a common test question in medical and nutrition biochemistry. Given Data / Assumptions: Lysine and leucine are purely ketogenic. Valine is purely glucogenic. Tryptophan and phenylalanine are both glucogenic and ketogenic. Concept / Approach: Classify the listed amino acids by catabolic endpoints. The hallmark of a purely ketogenic amino acid is exclusive conversion to acetyl-CoA/acetoacetyl-CoA without generating gluconeogenic intermediates. Lysine fits this definition. Tryptophan and phenylalanine generate mixed products, while valine is routed to succinyl-CoA and is glucogenic. Step-by-Step Solution: Recall the canonical list: lysine and leucine → ketogenic only.Identify valine → succinyl-CoA → glucogenic.Recognize tryptophan/phenylalanine → mixed endpoints (both).Select lysine as the purely ketogenic choice among the options. Verification / Alternative check: Metabolic pathway charts consistently annotate lysine as producing acetoacetyl-CoA, confirming its purely ketogenic status. Why Other Options Are Wrong: Tryptophan: yields both glucogenic and ketogenic products. Valine: glucogenic via propionyl-CoA to succinyl-CoA. Phenylalanine: both glucogenic and ketogenic (via fumarate and acetoacetate). None of these: incorrect because lysine is correct. Common Pitfalls: Memorization errors mixing leucine/lysine with other essential amino acids; always anchor the rule that leucine and lysine are the two purely ketogenic amino acids. Final Answer: Lysine

Question 8

Core definition: Transamination is best defined as the transfer of what to what during amino acid metabolism?

Accepted Answer

Introduction / Context: Transamination reactions are central to amino acid catabolism and biosynthesis. They allow the exchange of amino groups between amino acids and alpha-keto acids, maintaining nitrogen balance and funneling carbon skeletons into central metabolism. Aminotransferases (transaminases) catalyze these reversible reactions using the coenzyme pyridoxal phosphate (PLP). Given Data / Assumptions: Transamination conserves nitrogen by transferring, not releasing, the amino group. Typical pairs include glutamate/alpha-ketoglutarate and alanine/pyruvate. Ammonia release occurs primarily in oxidative deamination (e.g., glutamate dehydrogenase), not in transamination. Concept / Approach: Define precisely what moves in the reaction. In transamination, the alpha-amino group of a donor amino acid is transferred to an acceptor alpha-keto acid, forming a new amino acid and a new keto acid. No net free ammonia is produced in this step. PLP acts as a transient Schiff base carrier of the amino group during the ping-pong mechanism of the enzyme. Step-by-Step Solution: Start with amino acid 1 + alpha-keto acid 2.Transfer the amino group from amino acid 1 to alpha-keto acid 2 (via PLP).Form amino acid 2 + alpha-keto acid 1.Recognize there is no direct ammonia release in this step. Verification / Alternative check: Laboratory assays for ALT (alanine aminotransferase) and AST (aspartate aminotransferase) use this chemistry diagnostically to evaluate hepatocellular injury, underscoring the reaction's physiological importance. Why Other Options Are Wrong: Options involving ammonia release describe deamination, not transamination. Transfers to a carboxylic acid are incorrect; the acceptor is an alpha-keto acid. Carboxyl group transfer is not the defining feature of transamination. Common Pitfalls: Confusing transamination with oxidative deamination or the urea cycle; keep in mind that transamination shuttles amino groups without producing free ammonia. Final Answer: An amino group from an amino acid to a keto acid

Question 9

Phenylketonuria (PKU): In classical PKU due to phenylalanine hydroxylase deficiency, which aberrant metabolite is formed from phenylalanine?

Accepted Answer

Introduction / Context: Phenylketonuria (PKU) is a classic inborn error of metabolism characterized by deficient phenylalanine hydroxylase (or its cofactor tetrahydrobiopterin in some variants). Without conversion of phenylalanine to tyrosine, excess phenylalanine is shunted into alternative pathways, producing phenylketones that can be detected in urine and contribute to neurotoxicity if untreated. Given Data / Assumptions: Phenylalanine hydroxylase normally converts phenylalanine to tyrosine. In PKU, this primary route is blocked. Alternate transamination of phenylalanine generates phenylpyruvate, which can be further reduced or decarboxylated to phenyllactate and phenylacetate. Concept / Approach: Identify the metabolic detour that occurs when the primary hydroxylation step is impaired. The amino group of phenylalanine is transferred to alpha-ketoglutarate, forming phenylpyruvate and glutamate via an aminotransferase. Elevated phenylalanine and its keto-acid derivatives are typical laboratory findings in untreated PKU, explaining the term phenylketonuria (phenyl ketones in urine). Step-by-Step Solution: Recognize the blocked step: phenylalanine → tyrosine (deficient).Follow the alternative: phenylalanine → phenylpyruvate (via transamination).Appreciate downstream products: phenylacetate, phenyllactate.Connect metabolite buildup with clinical features and screening tests. Verification / Alternative check: Newborn screening measures elevated phenylalanine; urinary analysis may reveal phenylketones. Dietary restriction of phenylalanine and tyrosine supplementation improve outcomes, confirming pathway logic. Why Other Options Are Wrong: Isoleucine formation from phenylalanine does not occur. Reverse reactions listed are not physiologic. Phenylalanine → tyrosine is the normal (defective) step, not the aberrant product in PKU. Common Pitfalls: Confusing classical PAH deficiency with BH4 deficiency; both elevate phenylalanine, but the core detour to phenylpyruvate remains a defining biochemical feature. Final Answer: Phenylalanine to phenylpyruvate

Question 10

PKU and dietary load: In a person with phenylketonuria who consumes foods high in phenylalanine, which metabolite would most characteristically accumulate?

Accepted Answer

Introduction / Context: Dietary management of phenylketonuria (PKU) aims to prevent accumulation of phenylalanine and its toxic derivatives. When intake exceeds metabolic capacity due to phenylalanine hydroxylase deficiency, alternative catabolic routes dominate, producing characteristic metabolites that can be measured clinically and that contribute to neuropathology if levels remain high. Given Data / Assumptions: Classical PKU blocks phenylalanine → tyrosine conversion. Transamination of excess phenylalanine forms phenylpyruvate. Phenylpyruvate can be further reduced to phenyllactate or converted to phenylacetate. Concept / Approach: Under a high-phenylalanine load, the first and most proximate abnormal product is phenylpyruvate. Although phenylalanine itself also rises, the question asks for the metabolite that characteristically accumulates downstream in PKU. Urinary phenylketones (phenylpyruvate, phenylacetate, phenyllactate) give the disorder its name and are detectable in screening tests. Step-by-Step Solution: Block the primary route (phenylalanine hydroxylase).Shunt phenylalanine via transamination to phenylpyruvate.Recognize phenylpyruvate as the hallmark abnormal metabolite.Acknowledge further conversions to phenyllactate and phenylacetate. Verification / Alternative check: Biochemical profiling in untreated PKU shows elevated plasma phenylalanine and increased urinary phenylpyruvate; dietary restriction reduces these levels and prevents neurocognitive impairment. Why Other Options Are Wrong: Tyrosine tends to be low or normal in classical PKU. Isoleucine is unrelated to phenylalanine catabolism. Phenylacetate may rise but is downstream; phenylpyruvate is the immediate, signature keto-acid. Common Pitfalls: Answering with phenylalanine itself; while elevated, the question focuses on the characteristic metabolite produced by the aberrant pathway. Final Answer: Phenylpyruvate

Question 11

Transamination concept check: Which statement correctly describes what happens during a transamination reaction?

Accepted Answer

Introduction / Context: Transamination reactions redistribute nitrogen among amino acids and alpha-keto acids without releasing ammonia. They are catalyzed by aminotransferases using pyridoxal phosphate (PLP) and are vital for both amino acid catabolism and biosynthesis, as well as for shuttling nitrogen into glutamate before urea formation. Given Data / Assumptions: Transamination is typically reversible. Free ammonia is not produced directly in transamination. Common pairs include alanine/pyruvate and glutamate/alpha-ketoglutarate. Concept / Approach: Define what is transferred and between which molecules. The alpha-amino group moves from a donor amino acid to an acceptor alpha-keto acid, yielding a new amino acid and a new alpha-keto acid. This contrasts with oxidative deamination, which removes the amino group to free ammonia, and with peptide bond formation, which is a ribosomal process and not a transamination. Step-by-Step Solution: Write the general pattern: amino acid 1 + alpha-keto acid 2 ⇄ alpha-keto acid 1 + amino acid 2.Note PLP as the coenzyme forming a Schiff base intermediate (internal and external aldimines).Emphasize that no free NH3 is released in this step.Relate this to nitrogen funneling into glutamate for subsequent deamination by glutamate dehydrogenase. Verification / Alternative check: Enzyme assays for ALT and AST, used clinically in liver function testing, directly measure transamination activities, supporting the defined chemistry. Why Other Options Are Wrong: Carboxyl group transfer: not the defining feature of transamination. Removal of the amino group as ammonia: describes oxidative deamination. Polymerization into peptides: describes translation, not transamination. Oxygen transfer from keto acids: not a standard step in transamination. Common Pitfalls: Mixing up transamination with deamination or transamidation; remember that in transamination the nitrogen stays organic, simply changing partners. Final Answer: An amino group is transferred from an amino acid to an alpha-keto acid to form a new amino acid

Question 12

Classification by fate: Lysine is degraded to acetoacetyl-CoA. Based on this endpoint, how is lysine classified?

Accepted Answer

Introduction / Context: Amino acid classification hinges on carbon fate after nitrogen removal. If the carbon skeleton yields acetyl-CoA or acetoacetyl-CoA, the amino acid is ketogenic because these products cannot provide net carbons for glucose synthesis in humans. Lysine is a classic example, along with leucine. Given Data / Assumptions: Lysine catabolism proceeds to acetoacetyl-CoA. Acetoacetyl-CoA contributes to ketone body formation and lipid synthesis. No net gluconeogenesis occurs from acetyl-derived carbons in animals. Concept / Approach: Match the endpoint to the classification scheme. Because acetoacetyl-CoA is a ketogenic product, lysine is labeled ketogenic-only. This differs from dual-fate amino acids (e.g., isoleucine, phenylalanine) that produce both TCA intermediates (glucogenic) and acetyl-derived products (ketogenic). Step-by-Step Solution: Identify lysine's catabolic product: acetoacetyl-CoA.Relate acetoacetyl-CoA to ketone body pathways (acetoacetate, beta-hydroxybutyrate).Exclude any route to net oxaloacetate formation.Conclude lysine is ketogenic. Verification / Alternative check: Standard pathway charts and clinical nutrition references classify lysine and leucine as the two purely ketogenic amino acids, corroborating this answer. Why Other Options Are Wrong: Glucogenic: would require formation of pyruvate or TCA intermediates. Both equally: lysine is not dual-fate. None of these / invented terms: do not reflect accepted biochemical categories. Common Pitfalls: Assuming essential amino acids are all glucogenic; essentiality does not determine glucogenic or ketogenic status. Final Answer: Ketogenic amino acid

Question 13

PKU pathway block: A person with phenylketonuria cannot carry out which normal step in phenylalanine metabolism?

Accepted Answer

Introduction / Context: Classical phenylketonuria (PKU) results from deficiency of phenylalanine hydroxylase or its cofactor tetrahydrobiopterin, blocking the hydroxylation of phenylalanine to tyrosine. Recognizing the precise blocked step is vital for understanding dietary therapy and the biochemical basis of newborn screening programs. Given Data / Assumptions: Phenylalanine hydroxylase normally produces tyrosine from phenylalanine. In PKU, this conversion is impaired, elevating phenylalanine. Alternative metabolites (phenylpyruvate, phenyllactate, phenylacetate) accumulate. Concept / Approach: Identify the specific enzyme-catalyzed step that fails. The phenylalanine → tyrosine reaction is the first and key step of phenylalanine catabolism toward fumarate and acetoacetate. Other pairings in the options are not physiological conversions or refer to later steps not directly blocked by PAH deficiency. Step-by-Step Solution: Locate the normal pathway: phenylalanine → tyrosine → p-hydroxyphenylpyruvate → homogentisate → maleylacetoacetate → fumarylacetoacetate → fumarate + acetoacetate.Recognize the PKU block at the first step.Predict accumulation of phenylalanine and appearance of phenylketones.Select the blocked conversion accordingly. Verification / Alternative check: Elevated blood phenylalanine with low/normal tyrosine in newborn screening confirms the impaired phenylalanine → tyrosine step; dietary therapy reduces phenylalanine load and supplies tyrosine as a semiessential amino acid in PKU. Why Other Options Are Wrong: Phenylalanine to isoleucine/lysine: not a metabolic conversion. Phenol into ketones: not relevant to amino acid catabolism. Tyrosine to fumarate: occurs downstream, not the defining PKU block. Common Pitfalls: Assuming PKU blocks later aromatic steps; the defect is at the very first hydroxylation reaction. Final Answer: Phenylalanine to tyrosine

Question 14

Normal phenylalanine catabolism: At the first committed step of phenylalanine breakdown in humans, phenylalanine is initially converted to which compound?

Accepted Answer

Introduction / Context: Understanding the normal pathway of phenylalanine catabolism clarifies multiple inherited disorders, including PKU and tyrosinemias. The very first step sets the stage for subsequent ring-cleavage reactions that eventually yield both glucogenic and ketogenic end products. Given Data / Assumptions: Phenylalanine hydroxylase in the liver converts phenylalanine to tyrosine. This step requires the cofactor tetrahydrobiopterin, molecular oxygen, and iron. Downstream, tyrosine is further degraded toward fumarate (glucogenic) and acetoacetate (ketogenic). Concept / Approach: Identify the immediate product of the PAH-catalyzed reaction. The initial hydroxylation adds a hydroxyl group to the phenyl ring, producing tyrosine (p-hydroxyphenylalanine). Only afterward do transamination and ring-cleavage steps generate keto-acids and TCA intermediates. Therefore, tyrosine is the correct first product, not fumarate or phenylpyruvate. Step-by-Step Solution: Write the first step: phenylalanine + O2 + BH4 → tyrosine + H2O + BH2.Follow downstream: tyrosine → p-hydroxyphenylpyruvate → homogentisate → maleylacetoacetate → fumarylacetoacetate → fumarate + acetoacetate.Note dual fate: fumarate is glucogenic; acetoacetate is ketogenic.Select tyrosine as the initial product. Verification / Alternative check: Deficiency of phenylalanine hydroxylase leads to PKU with elevated phenylalanine and low/normal tyrosine, reinforcing that tyrosine is the normal first product in phenylalanine breakdown. Why Other Options Are Wrong: Fumarate: a later product after multiple steps. Phenylpyruvate: an abnormal side product seen in PKU, not the normal first step. Lysine and acetoacetate: not immediate products of the initial reaction. Common Pitfalls: Confusing the normal initial step with the alternative pathway active in PKU; remember that phenylpyruvate appears only when hydroxylation fails. Final Answer: Tyrosine

Question 15

Amino acid metabolism — identifying amino acids that are both ketogenic and glucogenic  Which of the following amino acids is classified as both ketogenic (yielding acetoacetyl CoA/acetyl CoA) and glucogenic (yielding TCA intermediates for gluconeog…

Accepted Answer

Introduction / Context: Amino acids are categorized as glucogenic, ketogenic, or both based on the metabolic fate of their carbon skeletons after deamination. This classification is important in biochemistry and clinical nutrition, especially for understanding fasting metabolism, inborn errors, and dietary planning for certain metabolic diseases. The question tests recognition of amino acids that can contribute carbon to glucose synthesis and also to ketone body or fatty acid synthesis. Given Data / Assumptions: Glucogenic amino acids yield pyruvate or TCA intermediates (e.g., oxaloacetate, alpha-ketoglutarate) that can form glucose. Ketogenic amino acids yield acetyl CoA or acetoacetyl CoA, precursors of ketone bodies and fatty acids. Some amino acids can be both, producing a mix of these products. Concept / Approach: To answer correctly, recall the standard classification: leucine and lysine are strictly ketogenic; valine, histidine, methionine are strictly glucogenic; isoleucine, phenylalanine, tyrosine, tryptophan, and threonine are both ketogenic and glucogenic. Therefore, among the options, tryptophan is the correct dual-class amino acid. Step-by-Step Solution: List strictly ketogenic: leucine, lysine.List strictly glucogenic: valine (→ succinyl CoA), among others.Recall dual-category group: isoleucine, phenylalanine, tyrosine, tryptophan, threonine.Match with options: tryptophan is both ketogenic and glucogenic. Verification / Alternative check: Pathway maps show tryptophan degradation produces alanine/pyruvate pathway intermediates (glucogenic) and acetoacetyl CoA (ketogenic), confirming its dual status. Why Other Options Are Wrong: Valine is glucogenic only (→ succinyl CoA). Lysine is ketogenic only (→ acetoacetyl CoA). Leucine (added distractor) is also strictly ketogenic. “None of these” is incorrect because tryptophan fits. Common Pitfalls: Memorizing only leucine and lysine as ketogenic and forgetting the broader “both” category, or misplacing valine into the dual list. Final Answer: Tryptophan

Question 16

Clinical enzymology — primary sites of transaminase (aminotransferase) activity  Transaminase enzymes (ALT/SGPT and AST/SGOT) are abundantly present in which organ under normal physiology and are widely used as diagnostic markers for injury?

Accepted Answer

Introduction / Context: Aminotransferases (transaminases) catalyze the transfer of amino groups between amino acids and alpha-keto acids. Two clinically important enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Their tissue distribution underlies their diagnostic value in assessing organ injury, especially hepatocellular damage. Given Data / Assumptions: ALT and AST are intracellular enzymes involved in amino acid metabolism and the malate–aspartate shuttle. Serum levels rise when cells are damaged and release enzymes. The liver contains high activity of both enzymes, particularly ALT. Concept / Approach: Identify the organ with the highest diagnostic relevance for transaminases. While AST appears in multiple tissues (heart, muscle, liver), ALT is more liver specific. Hence, in routine clinical practice, elevations of ALT and AST point strongly toward liver injury (hepatitis, ischemia, toxins). Therefore, the best single answer from the list is “Liver.” Step-by-Step Solution: Recall enzyme names: ALT (alanine aminotransferase), AST (aspartate aminotransferase).Consider tissue distribution: both abundant in hepatocytes.Relate to diagnostics: serum ALT/AST increases indicate hepatocellular damage.Select the organ most associated with these markers: liver. Verification / Alternative check: Clinical reference ranges and interpretation guides emphasize ALT as liver-predominant; AST, while less specific, also rises in liver damage, supporting the organ association. Why Other Options Are Wrong: Pancreas and intestine possess various enzymes (e.g., amylase, lipase, peptidases) but are not the classic focus of ALT/AST diagnostics. “None of these” ignores well-established clinical practice. Kidney cortex has aminotransferases but is not the primary association for diagnostic purposes. Common Pitfalls: Confusing AST’s broader distribution with specificity; the question asks for logical association used in diagnostics, which points to liver. Final Answer: Liver

Question 17

Nitrogen metabolism — recognizing oxidative deamination vs transamination  Which reaction is a correct example of oxidative deamination (removal of an amino group with concurrent oxidation), rather than transamination?

Accepted Answer

Introduction / Context: Nitrogen removal from amino acids occurs by two major mechanisms: transamination (amino group transfer) and oxidative deamination (amino group release as free ammonia with oxidation of the carbon skeleton). Distinguishing these pathways is fundamental for understanding the urea cycle and hepatic nitrogen handling. Given Data / Assumptions: Glutamate dehydrogenase catalyzes oxidative deamination of glutamate to alpha-ketoglutarate + NH3 with NAD+ or NADP+ as cofactor. Transaminases swap amino groups between amino acids and alpha-keto acids without releasing free ammonia. Non-physiologic substrate pairings are implausible in core amino acid pathways. Concept / Approach: Scan each reaction: if NH3 is released and the amino acid carbon becomes an alpha-keto acid, it is oxidative deamination. If amino groups are exchanged between partners with no free ammonia, it is transamination. Only the glutamate → alpha-ketoglutarate + NH3 reaction matches oxidative deamination. Step-by-Step Solution: Identify hallmark: free NH3 generation with oxidation.Recognize enzyme: glutamate dehydrogenase acts on glutamate to form alpha-ketoglutarate.Reject transamination examples: aspartate + alpha-ketoglutarate ↔ glutamate + oxaloacetate.Eliminate chemically implausible pairs (hexanoic acid reactions). Verification / Alternative check: Standard hepatic nitrogen flow: most amino acids first undergo transamination to glutamate; glutamate then undergoes oxidative deamination, releasing NH3 for urea synthesis. Why Other Options Are Wrong: Option B and E are transamination reactions. Options A and D include hexanoic acid, a fatty acid, not an alpha-keto acid partner in amino transfer, making them incorrect. Common Pitfalls: Assuming any ammonia release equals oxidative “deamination” without checking the carbon skeleton product, or accepting unrealistic reaction partners. Final Answer: Glutamate → alpha-ketoglutarate + NH3

Question 18

Definition check — what is oxidative deamination?  Oxidative deamination is best described as the conversion of an amino acid into which set of products?

Accepted Answer

Introduction / Context: Oxidative deamination removes an amino group from an amino acid while oxidizing the carbon skeleton, typically generating a corresponding alpha-keto acid and free ammonia. This reaction is central to hepatic nitrogen disposal and integration with the tricarboxylic acid cycle via alpha-ketoglutarate and other intermediates. Given Data / Assumptions: Glutamate dehydrogenase is the prototypical enzyme catalyzing oxidative deamination. NAD+ or NADP+ accepts electrons in the process. Free ammonia is produced for conversion to urea in the liver. Concept / Approach: Differentiate oxidative deamination from transamination. Transamination transfers amino groups between amino acids and alpha-keto acids without releasing ammonia. Oxidative deamination releases ammonia and produces a keto acid from the original amino acid carbon skeleton. Step-by-Step Solution: Identify reactant: an amino acid (e.g., glutamate).Apply oxidation with deamination: remove NH3 while oxidizing the alpha-carbon.Obtain products: corresponding alpha-keto acid (e.g., alpha-ketoglutarate) + NH3.Select the definition that matches these products. Verification / Alternative check: Enzymatic assays for glutamate dehydrogenase demonstrate stoichiometric production of NH3 and alpha-keto acids, confirming the definition. Why Other Options Are Wrong: Option A describes transamination, not oxidative deamination. Options B and E propose products (carboxylic acid or aldehyde) that are not standard outcomes. Option D misconstrues the chemistry. Common Pitfalls: Mixing up “transfer” (transamination) with “release” (oxidative deamination) of ammonia. Final Answer: Amino acid converted to a keto acid plus ammonia

Question 19

Catabolic fate of tyrosine — classification by products  Tyrosine catabolism yields acetoacetyl CoA (ketogenic) and fumarate (glucogenic). How is tyrosine therefore classified?

Accepted Answer

Introduction / Context: Amino acid classification by end products clarifies how their carbon contributes to energy metabolism. Tyrosine, derived from phenylalanine, degrades to both acetoacetyl CoA (a ketone body precursor) and fumarate (an anaplerotic TCA intermediate). This dual fate defines its category and has clinical implications in metabolic disorders like tyrosinemia and PKU. Given Data / Assumptions: Acetoacetyl CoA contributes to ketogenesis and lipid synthesis (ketogenic). Fumarate enters the TCA cycle and supports gluconeogenesis via oxaloacetate (glucogenic). Classification reflects carbon skeleton outcomes after deamination and side-chain breakdown. Concept / Approach: If an amino acid yields both acetyl/acetoacetyl CoA and TCA cycle intermediates, it is both ketogenic and glucogenic. Tyrosine meets this criterion based on its pathway through homogentisate and subsequent cleavage steps. Step-by-Step Solution: Recall tyrosine degradation route: tyrosine → p-hydroxyphenylpyruvate → homogentisate → maleylacetoacetate.Downstream cleavage: forms fumarate and acetoacetate (→ acetoacetyl CoA).Assign classification: ketogenic (acetoacetate) + glucogenic (fumarate).Select the option indicating both categories. Verification / Alternative check: Biochemical maps consistently place tyrosine (and phenylalanine) in the “both” list along with tryptophan, isoleucine, and threonine. Why Other Options Are Wrong: Options A and B consider only one product class. Option D is informal and not a standard category. Option E contradicts known metabolism. Common Pitfalls: Confusing tyrosine with lysine or leucine (strictly ketogenic) or with valine (strictly glucogenic). Final Answer: Ketogenic and glucogenic amino acid

Question 20

Phenylalanine metabolism — identifying a more toxic metabolite  In disorders of phenylalanine metabolism (e.g., phenylketonuria), accumulation of which compound is considered particularly toxic to the nervous system?

Accepted Answer

Introduction / Context: Phenylketonuria (PKU) is characterized by deficient phenylalanine hydroxylase activity, leading to the accumulation of phenylalanine and its alternative transamination products. Among these, phenylpyruvate and related metabolites (phenyllactate, phenylacetate) contribute significantly to neurotoxicity and the classic “mousy” odor. Recognizing the most problematic metabolite aids in understanding pathophysiology and rationale for dietary therapy. Given Data / Assumptions: PKU diverts phenylalanine toward transamination producing phenylpyruvate. Elevated phenylketones interfere with brain development and neurotransmitter balance. Tyrosine becomes conditionally essential in PKU management. Concept / Approach: Although high phenylalanine is harmful, the keto acid phenylpyruvate and its derivatives are particularly implicated in neurotoxicity. These compounds disrupt myelination and neurotransmitter synthesis and can be detected in urine (“phenylketones”). Therefore, phenylpyruvate is the best answer when asked to identify the most toxic compound among common choices. Step-by-Step Solution: Note enzyme defect: phenylalanine hydroxylase deficiency.Alternative pathway: phenylalanine → phenylpyruvate via transaminase.Downstream metabolites: phenylacetate and phenyllactate contribute to toxicity.Select phenylpyruvate as the key toxic metabolite. Verification / Alternative check: Clinical testing reveals elevated urinary phenylketones; dietary restriction of phenylalanine reduces phenylpyruvate levels and improves outcomes, corroborating its central role. Why Other Options Are Wrong: Tyrosine is a downstream product and therapeutic supplement in PKU; lysine is unrelated; phenylalanine is elevated but the question asks for the most toxic compound among listed, highlighting phenylpyruvate; acetoacetate is a ketone body not specific to PKU toxicity. Common Pitfalls: Equating the highest concentration (phenylalanine) with the principal toxin without considering metabolite potency. Final Answer: Phenylpyruvate

Amino Acid Metabolism Questions