A 47-year-old homeless man is brought to the emergency department by police, who found him sleeping by the side of the street. He is somnolent and confused and is unable to give a reliable history. His medical history is unobtainable. Vital signs include: temperature 36.9°C (98.4°F), blood pressure 112/75 mm Hg, and pulse 85/min. Physical examination reveals that he has severe truncal ataxia and horizontal gaze palsy with impaired vestibulo-ocular reflexes. Muscle stretch reflexes and motor strength are normal. He has no sensory deficits. Which of the following best represents the most likely etiology of this patient’s condition?
Q102
A 32-year-old woman comes to the physician for genetic consultation. She has a history of recurrent generalized seizures, diffuse muscular weakness, and multiple episodes of transient left-sided paresis. She has been hospitalized several times for severe lactic acidosis requiring intravenous fluid hydration. Her 10-year-old daughter also has seizures and muscle weakness. Her 7-year-old son has occasional muscle weakness and headaches but has never had a seizure. Pathologic examination of a biopsy specimen from the woman's soleus muscle shows ragged-appearing muscle fibers. Genetic analysis of the patient's son is most likely to show which of the following?
Q103
A homeless woman presents with shortness of breath on exertion and pedal edema. Cardiac workup performed shows evidence of dilated cardiomyopathy and increased cardiac output. She also has decreased sensation over both extremities bilaterally. Which vitamin deficiency most likely caused these symptoms?
Q104
A student is experimenting with the effects of nitric oxide in the body. He used a variety of amino acid isolates and measured the resulting nitric oxide levels and the physiological effects on the body. The amino acids function as substrates for nitric oxide synthase. After supplement administration, blood vessels dilated, and the systemic blood pressure decreased. Which of the following amino acids was used in this study?
Q105
A 52-year-old man comes to the physician because of a 4-month history of fatigue, weakness, constipation, decreased appetite, and intermittent flank pain. He takes ibuprofen for knee and shoulder pain. Physical examination shows mild tenderness bilaterally in the costovertebral areas. His serum calcium concentration is 11.2 mg/dL, phosphorus concentration is 2.5 mg/dL, and N-terminal parathyroid hormone concentration is 830 pg/mL. Which of the following steps in vitamin D metabolism is most likely increased in this patient?
Q106
A 45-year-old man presents with lethargy, muscle aches, and dry skin. He is underweight and has very particular eating habits. Physical examination reveals swollen bleeding gums, cracked lips, petechiae, perifollicular hemorrhage, and corkscrew hairs. Laboratory tests reveal a nutritional deficiency. Which of the following is the key function of the most likely deficient nutrient?
Q107
A 1-year-old boy is brought to the physician by his parents for the evaluation of recurrent seizures. He is at the 5th percentile for height and 10th percentile for weight. Examination shows coarse pale hair, inelastic hypopigmented skin, and generalized hypotonia. Laboratory studies show low serum ceruloplasmin levels. Decreased activity of which of the following enzymes is most likely responsible for this patient's condition?
Q108
A 55-year-old woman presents to her primary care physician with diarrhea. She states that it has persisted for the past several weeks and has not been improving. She also endorses episodes of feeling particularly flushed in the face. Her temperature is 99°F (37.2°C), blood pressure is 125/63 mmHg, pulse is 100/min, respirations are 15/min, and oxygen saturation is 97% on room air. Physical exam is notable for wheezing on pulmonary exam. The patient is discharged with medications for her symptoms. She returns 2 weeks later with symptoms of diarrhea, dry skin, a non-specific rash, and a notable decline in her memory. Which of the following is the most likely cause of this patient’s most recent presentation?
Q109
A 34-year-old man is admitted to the hospital because of a 3-week history of abdominal distention and yellowing of the skin. He also has a 2-year history of progressively worsening breathlessness and cough. Three days after admission, he suddenly develops peritonitis and sepsis. Despite appropriate care, he dies. At autopsy, histopathological examination of liver and lung tissue shows periodic acid-Schiff-positive (PAS-positive) globules within periportal hepatocytes and low levels of a protein that is responsible for the recoil of the lungs during expiration. Which of the following processes most likely contributes to the elastic properties of this protein?
Q110
A 49-year-old man is brought to the emergency department after being discovered unconscious in a field near the county fair. Several empty bottles of vodka were found near him. On arrival, he is mumbling incoherently. He appears malodorous and disheveled. Serum studies show:
Na+ 150 mEq/L
K+ 3.3 mEq/L
Cl- 115 mEq/L
HCO3- 13 mEq/L
Urea nitrogen 30 mg/dL
Glucose 75 mg/dL
Creatinine 1.4 mg/dL
Lactic acid 6 mmol/L (N < 2)
Which of the following changes to enzyme activity best explains this patient's laboratory findings?
Metabolism US Medical PG Practice Questions and MCQs
Question 101: A 47-year-old homeless man is brought to the emergency department by police, who found him sleeping by the side of the street. He is somnolent and confused and is unable to give a reliable history. His medical history is unobtainable. Vital signs include: temperature 36.9°C (98.4°F), blood pressure 112/75 mm Hg, and pulse 85/min. Physical examination reveals that he has severe truncal ataxia and horizontal gaze palsy with impaired vestibulo-ocular reflexes. Muscle stretch reflexes and motor strength are normal. He has no sensory deficits. Which of the following best represents the most likely etiology of this patient’s condition?
A. Miller-Fisher syndrome
B. Vitamin B1 deficiency (Correct Answer)
C. Vitamin B12 deficiency
D. Delirium tremens
E. Ethylene glycol intoxication
Explanation: ***Vitamin B1 deficiency***
- The patient's **somnolence, confusion, truncal ataxia, and horizontal gaze palsy** are classic symptoms of **Wernicke encephalopathy**, which is caused by acute **thiamine (vitamin B1) deficiency**.
- This condition is common in individuals with **alcohol use disorder** or malnutrition, as the patient's homeless status suggests.
*Miller-Fisher syndrome*
- This is a rare variant of **Guillain-Barré syndrome** characterized by the triad of **ataxia, areflexia, and ophthalmoplegia**.
- While ophthalmoplegia and ataxia are present, the patient's **normal muscle stretch reflexes** and lack of significant **motor weakness** make this diagnosis less likely.
*Vitamin B12 deficiency*
- Leads to **subacute combined degeneration** of the spinal cord, causing **ataxia, paresthesias, weakness, and loss of proprioception and vibratory sensation**.
- The acute presentation with **gaze palsy** and the absence of sensory deficits or significant motor weakness make this less probable.
*Delirium tremens*
- Typically occurs due to **severe alcohol withdrawal** and presents with **agitation, hallucinations, tremors, and autonomic instability** (e.g., fever, tachycardia, hypertension).
- The patient's presentation of somnolence, confusion, ataxia, and gaze palsy is not typical for delirium tremens.
*Ethylene glycol intoxication*
- Can cause **neurological symptoms** like altered mental status and ataxia, and in severe cases, ophthalmoplegia due to **cranial nerve involvement**.
- However, it is also associated with **acute kidney injury, metabolic acidosis with a high anion gap, and calcium oxalate crystaluria**, none of which are indicated in the provided information.
Question 102: A 32-year-old woman comes to the physician for genetic consultation. She has a history of recurrent generalized seizures, diffuse muscular weakness, and multiple episodes of transient left-sided paresis. She has been hospitalized several times for severe lactic acidosis requiring intravenous fluid hydration. Her 10-year-old daughter also has seizures and muscle weakness. Her 7-year-old son has occasional muscle weakness and headaches but has never had a seizure. Pathologic examination of a biopsy specimen from the woman's soleus muscle shows ragged-appearing muscle fibers. Genetic analysis of the patient's son is most likely to show which of the following?
A. Mutation in DNA repair gene
B. Genetically distinct cell lines
C. Silenced paternal gene copy
D. Heterogenous mitochondrial DNA (Correct Answer)
E. Altered allele on the X chromosome
Explanation: ***Heterogenous mitochondrial DNA***
- This scenario describes **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)**, a mitochondrial disorder characterized by diverse symptoms.
- Due to **maternal inheritance**, all children of an affected mother inherit mitochondrial DNA, but the **heteroplasmy** (mix of normal and mutated mitochondrial DNA) can vary, leading to different disease severities, as seen in the son's milder symptoms.
*Mutation in DNA repair gene*
- Mutations in DNA repair genes are associated with conditions like **xeroderma pigmentosum** and **hereditary nonpolyposis colorectal cancer**.
- These conditions typically present with **increased cancer risk** and hypersensitivity to DNA-damaging agents, not the neurological and muscular symptoms described.
*Genetically distinct cell lines*
- This refers to **mosaicism**, where an individual has two or more genetically different sets of cells.
- While mosaicism can cause variable disease presentation, the inheritance pattern and specific symptoms (lactic acidosis, "ragged red fibers") are highly indicative of a mitochondrial disorder.
*Silenced paternal gene copy*
- This describes **genomic imprinting**, where one parent's gene copy is methylated and silenced.
- Conditions like **Prader-Willi** and **Angelman syndromes** arise from defects in imprinting, but their clinical features differ significantly from those presented here.
*Altered allele on the X chromosome*
- This refers to **X-linked inheritance**, seen in disorders like **Duchenne muscular dystrophy** or **fragile X syndrome**.
- X-linked disorders have distinct inheritance patterns (e.g., affected males, carrier females) and different clinical presentations compared to MELAS, which is maternally inherited.
Question 103: A homeless woman presents with shortness of breath on exertion and pedal edema. Cardiac workup performed shows evidence of dilated cardiomyopathy and increased cardiac output. She also has decreased sensation over both extremities bilaterally. Which vitamin deficiency most likely caused these symptoms?
A. Vitamin B6
B. Vitamin C
C. Vitamin B1 (Correct Answer)
D. Vitamin B3
E. Vitamin A
Explanation: ***Vitamin B1***
- The combination of **dilated cardiomyopathy**, **high-output heart failure** (manifesting as shortness of breath and pedal edema), and **peripheral neuropathy** (decreased sensation) is classic for **wet beriberi**, caused by thiamine (Vitamin B1) deficiency.
- **Homelessness** is a significant risk factor for nutritional deficiencies, including thiamine deficiency, due to inadequate diet.
*Vitamin B6*
- Deficiency can cause **peripheral neuropathy**, but it does not typically lead to **dilated cardiomyopathy** or **high-output heart failure**.
- Other manifestations of B6 deficiency include **sideroblastic anemia** and **seizures**.
*Vitamin C*
- Deficiency causes **scurvy**, characterized by **gingivitis**, **poor wound healing**, **petechiae**, and joint pain.
- It does not present with **cardiomyopathy** or **neuropathy** as described.
*Vitamin B3*
- Deficiency causes **pellagra**, characterized by the "3 Ds": **dermatitis**, **diarrhea**, and **dementia**.
- While it can affect the nervous system (dementia), it does not typically cause **dilated cardiomyopathy** or **peripheral neuropathy**.
*Vitamin A*
- Deficiency primarily affects **vision** (e.g., **night blindness**, **xerophthalmia**) and immune function.
- It is not associated with **cardiac** or **neurological symptoms** like those described in the patient.
Question 104: A student is experimenting with the effects of nitric oxide in the body. He used a variety of amino acid isolates and measured the resulting nitric oxide levels and the physiological effects on the body. The amino acids function as substrates for nitric oxide synthase. After supplement administration, blood vessels dilated, and the systemic blood pressure decreased. Which of the following amino acids was used in this study?
A. Histidine
B. Tyrosine
C. Methionine
D. Arginine (Correct Answer)
E. Leucine
Explanation: ***Arginine***
- **Arginine** is the direct precursor to **nitric oxide (NO)** through the action of **nitric oxide synthase (NOS)**.
- The production of NO leads to **vasodilation** and a subsequent decrease in **systemic blood pressure**, which aligns with the observed effects.
*Histidine*
- **Histidine** is a precursor for **histamine**, which can cause vasodilation, but it is not the direct substrate for **nitric oxide synthase**.
- Its primary role in NO synthesis is indirect, unlike arginine.
*Tyrosine*
- **Tyrosine** is a precursor for **catecholamines** like dopamine, norepinephrine, and epinephrine, which are involved in various physiological responses but not directly in **nitric oxide synthesis**.
- While catecholamines can affect blood pressure, their synthesis does not involve **nitric oxide synthase (NOS)** as a substrate.
*Methionine*
- **Methionine** is an essential amino acid primarily involved in **methylation reactions** and the synthesis of other sulfur-containing compounds.
- It does not directly serve as a substrate for **nitric oxide synthase** in the production of nitric oxide.
*Leucine*
- **Leucine** is a branched-chain amino acid (BCAA) primarily involved in **protein synthesis** and muscle metabolism.
- It does not serve as a substrate for **nitric oxide synthase** to produce nitric oxide.
Question 105: A 52-year-old man comes to the physician because of a 4-month history of fatigue, weakness, constipation, decreased appetite, and intermittent flank pain. He takes ibuprofen for knee and shoulder pain. Physical examination shows mild tenderness bilaterally in the costovertebral areas. His serum calcium concentration is 11.2 mg/dL, phosphorus concentration is 2.5 mg/dL, and N-terminal parathyroid hormone concentration is 830 pg/mL. Which of the following steps in vitamin D metabolism is most likely increased in this patient?
A. Ergocalciferol → 25-hydroxyergocalciferol
B. 7-dehydrocholesterol → cholecalciferol
C. 25-hydroxycholecalciferol → 1,25-dihydroxycholecalciferol (Correct Answer)
D. 25-hydroxycholecalciferol → 24,25-dihydroxycholecalciferol
E. Cholecalciferol → 25-hydroxycholecalciferol
Explanation: ***25-hydroxycholecalciferol → 1,25-dihydroxycholecalciferol***
- This patient presents with **hypercalcemia** (11.2 mg/dL), **hypophosphatemia** (2.5 mg/dL), and a markedly **elevated N-terminal parathyroid hormone (PTH)** concentration (830 pg/mL), which are classic findings for **primary hyperparathyroidism**.
- In primary hyperparathyroidism, elevated PTH directly stimulates the **renal 1-alpha-hydroxylase enzyme**, increasing the conversion of **25-hydroxycholecalciferol** (calcidiol) to its active form, **1,25-dihydroxycholecalciferol** (calcitriol), which raises calcium levels.
*Ergocalciferol → 25-hydroxyergocalciferol*
- This step involves the **hepatic 25-hydroxylase enzyme** converting dietary vitamin D2 (ergocalciferol) to its storage form, which is not primarily regulated by PTH in the context of hyperparathyroidism.
- While essential for vitamin D activation, this conversion rate is usually adequate and not the primary increased step responsible for the hypercalcemic state in this patient's presentation.
*7-dehydrocholesterol → cholecalciferol*
- This process is the **cutaneous synthesis of vitamin D3 (cholecalciferol)**, which is dependent on UV light exposure and is not directly regulated by PTH.
- This initial step of vitamin D synthesis occurs in the skin and is upstream of the metabolic pathway influenced by PTH.
*25-hydroxycholecalciferol → 24,25-dihydroxycholecalciferol*
- This conversion produces an **inactive form of vitamin D** and is catalyzed by the **24-hydroxylase enzyme**.
- This enzyme activity is typically **suppressed by high PTH** and **increased by high levels of 1,25-dihydroxycholecalciferol**, serving to degrade excess active vitamin D; therefore, this step would likely be decreased, not increased, in primary hyperparathyroidism.
*Cholecalciferol → 25-hydroxycholecalciferol*
- This is the **hepatic 25-hydroxylation** of vitamin D3, producing 25-hydroxycholecalciferol (calcidiol), the major circulating form of vitamin D.
- While critical for producing the substrate for further activation, this step is not the *most likely increased* step in response to high PTH in primary hyperparathyroidism.
Question 106: A 45-year-old man presents with lethargy, muscle aches, and dry skin. He is underweight and has very particular eating habits. Physical examination reveals swollen bleeding gums, cracked lips, petechiae, perifollicular hemorrhage, and corkscrew hairs. Laboratory tests reveal a nutritional deficiency. Which of the following is the key function of the most likely deficient nutrient?
A. Hydroxylation of lysine and proline residues in collagen synthesis (Correct Answer)
B. Precursor of serotonin
C. Component of the visual pigment rhodopsin
D. Gamma-carboxylation of glutamate residues in clotting factors
E. Cofactor in carboxylase reactions
Explanation: ***Hydroxylation of lysine and proline residues in collagen synthesis***
- The patient's symptoms of **swollen, bleeding gums**, **petechiae**, **perifollicular hemorrhage**, and **corkscrew hairs** are classic signs of **scurvy**, caused by a severe deficiency of **vitamin C**.
- **Vitamin C** (ascorbic acid) is a crucial **cofactor** for **prolyl hydroxylase** and **lysyl hydroxylase**, enzymes essential for the hydroxylation of **proline** and **lysine** residues in **collagen** synthesis, which stabilizes the collagen triple helix.
*Precursor of serotonin*
- **Serotonin** is synthesized from the amino acid **tryptophan**, not vitamin C.
- Deficiency of serotonin precursors is not associated with the bleeding and connective tissue problems observed in this patient.
*Component of the visual pigment rhodopsin*
- **Rhodopsin** is a visual pigment found in the retina, and its formation requires **vitamin A** (retinol).
- Deficiency of vitamin A leads to **night blindness** and xerophthalmia, not the symptoms described.
*Gamma-carboxylation of glutamate residues in clotting factors*
- This process is essential for the activation of several **blood clotting factors** (II, VII, IX, X) and is dependent on **vitamin K**.
- Vitamin K deficiency can lead to bleeding diathesis, but the specific mucocutaneous and follicular signs point away from this.
*Cofactor in carboxylase reactions*
- **Biotin** (vitamin B7) acts as a cofactor for **carboxylase enzymes**, which are involved in fatty acid synthesis, gluconeogenesis, and amino acid metabolism.
- While biotin deficiency can cause skin and hair problems, it does not typically present with the specific bleeding and perifollicular hemorrhages seen with scurvy.
Question 107: A 1-year-old boy is brought to the physician by his parents for the evaluation of recurrent seizures. He is at the 5th percentile for height and 10th percentile for weight. Examination shows coarse pale hair, inelastic hypopigmented skin, and generalized hypotonia. Laboratory studies show low serum ceruloplasmin levels. Decreased activity of which of the following enzymes is most likely responsible for this patient's condition?
A. Phenylalanine hydroxylase
B. Lysyl oxidase (Correct Answer)
C. Glucocerebrosidase
D. Prolyl hydroxylase
E. Homogentisate oxidase
Explanation: ***Lysyl oxidase***
- This patient's presentation with **recurrent seizures**, **growth failure**, **coarse pale hair**, **hypopigmented skin**, **generalized hypotonia**, and **low serum ceruloplasmin** is highly suggestive of **Menkes disease**.
- **Menkes disease** is an X-linked recessive disorder of copper metabolism, resulting from a defect in the **ATP7A gene**. This defect leads to impaired copper transport from intestinal cells, causing copper deficiency, which in turn reduces the activity of copper-dependent enzymes, including **lysyl oxidase**.
*Phenylalanine hydroxylase*
- A deficiency in **phenylalanine hydroxylase** causes **phenylketonuria (PKU)**, which involves an accumulation of phenylalanine.
- PKU typically presents with intellectual disability, seizures, and a musty odor, but not the specific skin and hair findings or low ceruloplasmin seen in this case.
*Glucocerebrosidase*
- A deficiency in **glucocerebrosidase** is responsible for **Gaucher disease**, a lysosomal storage disorder.
- Gaucher disease presents with hepatosplenomegaly, bone crises, and neurological symptoms in some types, which are not the primary features here.
*Prolyl hydroxylase*
- **Prolyl hydroxylase** is involved in the hydroxylation of proline residues during collagen synthesis.
- Deficiencies or dysfunction of this enzyme are typically associated with collagen disorders or scurvy (due to vitamin C deficiency affecting its activity) and do not manifest with the specific constellation of symptoms described.
*Homogentisate oxidase*
- A deficiency in **homogentisate oxidase** causes **alkaptonuria**.
- Alkaptonuria is characterized by dark urine upon standing, ochronosis (darkening of connective tissues), and arthritis in adulthood, which are not consistent with the patient's presentation.
Question 108: A 55-year-old woman presents to her primary care physician with diarrhea. She states that it has persisted for the past several weeks and has not been improving. She also endorses episodes of feeling particularly flushed in the face. Her temperature is 99°F (37.2°C), blood pressure is 125/63 mmHg, pulse is 100/min, respirations are 15/min, and oxygen saturation is 97% on room air. Physical exam is notable for wheezing on pulmonary exam. The patient is discharged with medications for her symptoms. She returns 2 weeks later with symptoms of diarrhea, dry skin, a non-specific rash, and a notable decline in her memory. Which of the following is the most likely cause of this patient’s most recent presentation?
A. Niacin deficiency (Correct Answer)
B. Increased vasoactive intestinal peptide levels
C. Increased catecholamine levels
D. Vitamin B12 deficiency
E. Increased serotonin levels
Explanation: ***Niacin deficiency***
- The patient's **most recent presentation** with the **\"3 Ds\" of pellagra**—**dermatitis** (dry skin, rash), **diarrhea**, and **dementia** (memory decline)—is characteristic of **niacin (Vitamin B3) deficiency**.
- The initial presentation (diarrhea, flushing, wheezing) suggests **carcinoid syndrome** from a carcinoid tumor secreting **serotonin**.
- **Carcinoid tumors consume large amounts of tryptophan** to produce serotonin, thereby **depleting the tryptophan pool** needed for **endogenous niacin synthesis**.
- This leads to **secondary niacin deficiency (pellagra)**, especially in patients with carcinoid syndrome, making niacin deficiency the cause of the **most recent symptoms** after the initial carcinoid presentation.
*Increased vasoactive intestinal peptide levels*
- Elevated **vasoactive intestinal peptide (VIP)** levels are seen in **VIPomas**, causing **watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome)**.
- While diarrhea is present, VIPoma does not explain the **flushing, wheezing, or the subsequent development of pellagra** (dermatitis and dementia).
*Increased catecholamine levels*
- Increased **catecholamine levels** are characteristic of **pheochromocytoma**, presenting with **paroxysmal hypertension, headaches, palpitations, and diaphoresis**.
- This does not explain the **diarrhea, flushing, wheezing, or pellagra symptoms** seen in this patient.
*Vitamin B12 deficiency*
- **Vitamin B12 deficiency** causes **megaloblastic anemia, subacute combined degeneration** (posterior column and corticospinal tract findings), **peripheral neuropathy, and glossitis**.
- The prominent **diarrhea, flushing, wheezing, and dermatitis** are not consistent with B12 deficiency.
*Increased serotonin levels*
- While elevated **serotonin levels** from **carcinoid syndrome** explain the **initial presentation** (diarrhea, flushing, bronchospasm), they do not directly explain the **most recent presentation**.
- The question specifically asks about the cause of the **most recent symptoms** (dry skin, rash, memory decline), which represent **pellagra from niacin deficiency**—a known complication of carcinoid syndrome due to tryptophan depletion for serotonin synthesis.
- The **niacin deficiency** is the proximate cause of the new symptoms, making it the better answer for "most recent presentation."
Question 109: A 34-year-old man is admitted to the hospital because of a 3-week history of abdominal distention and yellowing of the skin. He also has a 2-year history of progressively worsening breathlessness and cough. Three days after admission, he suddenly develops peritonitis and sepsis. Despite appropriate care, he dies. At autopsy, histopathological examination of liver and lung tissue shows periodic acid-Schiff-positive (PAS-positive) globules within periportal hepatocytes and low levels of a protein that is responsible for the recoil of the lungs during expiration. Which of the following processes most likely contributes to the elastic properties of this protein?
A. O-glycosylation of serine residues
B. Arrangement in a triple helical structure
C. Formation of disulfide bridges
D. Hydroxylation of proline residues
E. Oxidative deamination of lysine residues (Correct Answer)
Explanation: ***Oxidative deamination of lysine residues***
- The patient's presentation *abdominal distention*, *yellowing of skin*, *breathlessness*, *cough*, and *PAS-positive globules* in the liver, along with low levels of a protein responsible for lung recoil, are consistent with **alpha-1 antitrypsin deficiency (A1AD)**.
- The defective protein is **alpha-1 antitrypsin (A1AT)**, and the lung damage (emphysema) is due to uncontrolled **elastase activity**. The elastic properties of **elastin**, the protein responsible for lung recoil, are largely due to cross-linking of its polypeptide chains via **desmosine** and **isodesmosine** bridges, which are formed by the **oxidative deamination of lysine residues**.
*O-glycosylation of serine residues*
- **O-glycosylation** involves the addition of saccharides to the hydroxyl group of serine or threonine residues.
- While important for some proteins, this process is not responsible for the elastic properties of **elastin**.
*Arrangement in a triple helical structure*
- A **triple helical structure** is characteristic of **collagen**, providing tensile strength, not the elastic recoil of proteins like **elastin**.
- **Elastin** has a more random coil structure that allows it to stretch and recoil.
*Formation of disulfide bridges*
- **Disulfide bridges** (between cysteine residues) are crucial for stabilizing the tertiary and quaternary structures of many proteins.
- However, **elastin** is notably low in cysteine, and its elastic properties mainly arise from **lysine-derived cross-links**.
*Hydroxylation of proline residues*
- **Hydroxylation of proline** and lysine residues is essential for the stability and cross-linking of **collagen**, specifically in forming its triple helix.
- This modification is not the primary mechanism conferring elasticity to **elastin**.
Question 110: A 49-year-old man is brought to the emergency department after being discovered unconscious in a field near the county fair. Several empty bottles of vodka were found near him. On arrival, he is mumbling incoherently. He appears malodorous and disheveled. Serum studies show:
Na+ 150 mEq/L
K+ 3.3 mEq/L
Cl- 115 mEq/L
HCO3- 13 mEq/L
Urea nitrogen 30 mg/dL
Glucose 75 mg/dL
Creatinine 1.4 mg/dL
Lactic acid 6 mmol/L (N < 2)
Which of the following changes to enzyme activity best explains this patient's laboratory findings?
A. Increased activity of phenylalanine hydroxylase
B. Decreased activity of glucose-6-phosphate dehydrogenase
C. Decreased activity of phosphofructokinase-2
D. Decreased activity of pyruvate dehydrogenase (Correct Answer)
E. Increased activity of α-ketoglutarate dehydrogenase
Explanation: ***Decreased activity of pyruvate dehydrogenase***
- The patient presents with **lactic acidosis** (lactic acid 6 mmol/L) and a high anion gap metabolic acidosis (AG = Na - Cl - HCO3 = 150 - 115 - 13 = 22 mEq/L). **Alcohol consumption** can lead to an increased NADH/NAD+ ratio, which inhibits pyruvate dehydrogenase.
- Inhibition of **pyruvate dehydrogenase** prevents the conversion of pyruvate to acetyl-CoA, shunting pyruvate towards lactate via lactate dehydrogenase, which is enhanced by the high NADH levels.
*Increased activity of phenylalanine hydroxylase*
- **Phenylalanine hydroxylase** is involved in the metabolism of phenylalanine to tyrosine, and its increased activity is not associated with lactic acidosis.
- Defective phenylalanine hydroxylase leads to **phenylketonuria**, which presents differently.
*Decreased activity of glucose-6-phosphate dehydrogenase*
- **Glucose-6-phosphate dehydrogenase (G6PD)** deficiency leads to hemolytic anemia due to impaired NADPH production, making red blood cells susceptible to oxidative stress, and is not directly linked to lactic acidosis.
- It does not explain the observed electrolyte imbalances or elevated lactate levels.
*Decreased activity of phosphofructokinase-2*
- **Phosphofructokinase-2 (PFK-2)** regulates glycolysis by producing fructose-2,6-bisphosphate, which activates PFK-1. Decreased activity would generally *reduce* glycolysis rather than promote lactic acid buildup.
- A decrease in PFK-2 activity is not a primary cause of lactic acidosis in the context of alcohol intoxication.
*Increased activity of α-ketoglutarate dehydrogenase*
- **α-ketoglutarate dehydrogenase** is a key enzyme in the citric acid cycle. Increased activity would enhance the citric acid cycle, potentially *reducing* the accumulation of glycolytic intermediates, rather than causing lactic acidosis.
- Its increased activity would generally lead to more efficient energy production, not the metabolic derangements seen here.
