BIOCHEMSTRY Flashcards

Question

Antigens or antibodies are immobilized on a microtiter plate. A sample containing the target antigen or antibody is added, and it binds to the immobilized counterpart. An enzyme-linked secondary antibody that binds to the target is then added. A substrate for the enzyme is used to produce a colorimetric or fluorescent signal, which is measured to determine the amount of target present. What test is this?

Answer 1

ELISA (Enzyme-Linked Immunosorbent Assay)

Answer 2

Statins inhibit HMG-CoA reductase, an enzyme involved in the biosynthesis of cholesterol. This leads to decreased cholesterol levels in the liver and increased uptake of LDL cholesterol from the bloodstream.

Answer 3

Atorvastatin (Lipitor).

Answer 4

Muscle-related issues (myalgia, myopathy, and rhabdomyolysis), liver enzyme elevation, and gastrointestinal symptoms.

Answer 5

Rhabdomyolysis, characterized by the breakdown of muscle tissue, which can lead to acute kidney injury.

Answer 6

Statins reduce the risk of cardiovascular events (such as heart attacks and strokes) by lowering LDL cholesterol levels and stabilizing atherosclerotic plaques.

Answer 7

Rosuvastatin (Crestor).

Answer 8

Liver function tests (LFTs) to monitor for liver enzyme elevations and creatine kinase (CK) levels to check for muscle-related side effects.

Answer 9

Statins can interact with drugs that inhibit CYP3A4 (e.g., certain antibiotics and antifungals), which can increase statin levels and the risk of side effects. Examples include clarithromycin and ketoconazole.

Answer 10

Pravastatin.

Answer 11

* Diet modification (low saturated fat and cholesterol) * Regular exercise * Weight management * Smoking cessation.

Answer 12

A reduced FEV1/FVC ratio, typically less than 0.70 (70%).

Answer 13

In COPD, the improvement in FEV1 post-bronchodilator is typically less than 12% and 200 mL from baseline.

Answer 14

Group of progressive lung diseases characterized by chronic airflow limitation, including chronic bronchitis and emphysema. It is primarily caused by long-term exposure to irritants, such as smoking.

Answer 15

COPD involves chronic inflammation, increased mucus production, and destruction of lung tissue (emphysema), leading to airflow limitation and impaired gas exchange.

Answer 16

Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction, bronchial hyperreactivity, and increased mucus production, leading to wheezing, breathlessness, and cough.

Answer 17

Smoking, occupational exposure to dust or chemicals, alpha-1 antitrypsin deficiency, and environmental pollutants.

Answer 18

Allergens (e.g., pollen, dust mites), respiratory infections, exercise, cold air, and irritants such as smoke and pollution.

Answer 19

A reversible decrease in FEV1/FVC ratio with significant improvement (≥12% and 200 mL increase) after bronchodilator administration.

Answer 20

A reduced FEV1/FVC ratio (<0.70) indicating persistent airflow limitation.

Answer 21

Mild: FEV1 ≥ 80% of predicted Moderate: FEV1 50-79% of predicted Severe: FEV1 30-49% of predicted Very Severe: FEV1 < 30% of predicted or FEV1 < 50% with respiratory failure

Answer 22

Diagnosis is based on clinical symptoms and spirometry: * Reversible airflow obstruction (significant response to bronchodilators) * Peak flow variability.

Answer 23

* Corticoesteroid * Oxygen (advanced cases) * Pause smoking * Dialator (Bronchodilators:beta-agonists, anticholinergics)

Answer 24

Inhaled corticosteroids Beta-agonists for acute relief Leukotriene receptor antagonists Avoiding triggers.

Answer 25

The endoplasmic reticulum (ER) and mitochondria.

Answer 26

Calcium pumps (ATPases) actively transport calcium out of the cytosol into the ER, mitochondria, or extracellular space, and calcium channels regulate its flow across cell membranes.

Answer 27

Ischemia (reduced blood flow) or hypoxia (low oxygen levels) and cellular damage due to toxins or trauma.

Answer 28

Proteases, phospholipases, and endonucleases.

Answer 29

It causes the loss of mitochondrial membrane potential, disrupts ATP production, and leads to the release of cytochrome c, triggering apoptosis.

Answer 30

Elevated calcium can enhance the generation of reactive oxygen species (ROS), causing oxidative damage to lipids, proteins, and DNA.

Answer 31

Necrosis (unregulated cell death) and apoptosis (programmed cell death).

Answer 32

Sudden increases in calcium after restoring blood flow lead to ROS generation and enzyme activation, causing further cell damage.

Answer 33

Myocardial infarction, stroke, traumatic brain injury, and neurodegenerative diseases.

Answer 34

In necrosis, unregulated calcium influx causes cell swelling and membrane rupture; in apoptosis, calcium triggers mitochondrial damage and programmed cell death pathways.

Answer 35

Affinity refers to the **strength** with which a ligand (such as a drug or agonist) binds to its receptor. Higher affinity means stronger binding and often lower concentrations needed to achieve an effect.

Answer 36

An agonist is a substance that binds to a receptor and activates it to produce a biological response.

Answer 37

A GPCR is a cell surface receptor that, when activated by an agonist, interacts with G-proteins to trigger intracellular signaling pathways.

Answer 38

Activation of the 5-HT1B receptor, a GPCR, triggers the exchange of GDP for GTP on the G-protein, initiating downstream signaling cascades.

Answer 39

Km represents the concentration of a ligand needed to achieve half of the maximum receptor activity. A lower Km indicates a higher affinity of the ligand for the receptor.

Answer 40

A lower Km means that the drug has a higher affinity for the receptor, requiring a lower concentration to achieve half-maximal activation.

Answer 41

Vmax is the maximum rate of a reaction when the receptor is fully saturated with a ligand. It reflects the total receptor concentration and the intrinsic activity of the receptor-ligand complex.

Answer 42

No, Vmax depends on the total number of receptors and their intrinsic activity, not directly on the ligand's affinity.

Answer 43

Knowing Km and Vmax helps predict how drugs will behave in the body, determine dosing, understand therapeutic effects, and anticipate potential side effects.

Answer 44

The 5-HT1B receptor is a serotonin GPCR involved in neurotransmission, affecting mood, vasoconstriction, and other physiological functions.

Answer 45

Porphyrias are **metabolic disorders** caused by **enzyme deficiencies** in the **heme biosynthesis** pathway, leading to the **accumulation** of porphyrins or their precursors and resulting in clinical symptoms such as **photosensitivity** or **neurovisceral symptoms**.

Answer 46

The two main types are: * Acute porphyrias (neurovisceral symptoms) * Cutaneous porphyrias (photosensitivity and skin lesions).

Answer 47

Porphobilinogen deaminase.

Answer 48

* Severe abdominal pain * Neuropsychiatric disturbances (e.g., anxiety, depression, psychosis) * Peripheral neuropathy. (Patients do not have photosensitivity)

Answer 49

Increased levels of porphobilinogen and δ-aminolevulinic acid (ALA) in the urine.

Answer 50

Uroporphyrinogen decarboxylase.

Answer 51

* Photosensitivity * Blistering skin lesions on sun-exposed areas * Hyperpigmentation * Increased skin fragility. **P** hotosensitivity 🌞 expousured blistering **R** ise of skin fragility **P** igmenttation

Answer 52

Elevated levels of uroporphyrin in the urine.

Answer 53

Coproporphyrinogen oxidase.

Answer 54

* Alcohol consumption * Hepatitis C infection * Estrogen use

Answer 55

* Neurovisceral symptoms (similar to AIP) * Cutaneous photosensitivity.

Answer 56

Increased levels of coproporphyrin in urine and feces

Answer 57

Ferrochelatase

Answer 58

* Photosensitivity with non-blistering * Painful erythema * Swelling after sun exposure

Answer 59

Elevated levels of protoporphyrin in erythrocytes, plasma, and feces.

Answer 60

* Avoiding sun exposure * Using sunscreens * Hydroxychloroquine or * Phlebotomy to reduce porphyrin levels

Answer 61

* Avoiding **triggers** (e.g., certain drugs, alcohol, fasting) * Providing **glucose** to suppress heme synthesis * **Hemin** infusions to inhibit ALA synthase.

Answer 62

* Pink/red urine ("tea colored"): PCT (⬆︎uroporphyrin) * Dark urine ("Port-wine colored"): AIP (⬆︎porphobilinogen)

Answer 63

Inhibits: * Ferrochelatase * δ-aminolevulinic acid dehydratase (ALA dehydratase), ⬆︎ ALA and protoporphyrin = Anemia and Neurological symptoms.

Answer 64

Provides a negative feedback mechanism to inhibit ALA synthase. ⬇︎ production of toxic porphyrin precursors.

Answer 65

* Cutaneous porphyrias - photosensitivity and skin lesions. * Acute porphyrias - neurovisceral symptoms (e.g., abdominal pain, psychiatric symptoms, and neuropathy).

Answer 66

Genetic testing can confirm specific enzyme deficiencies and help identify asymptomatic carriers or individuals at risk for developing symptoms.

Answer 67

(B) Porphobilinogen deaminase This deficiency causes Acute Intermittent Porphyria (AIP), characterized by severe abdominal pain, neurological symptoms, and increased porphobilinogen levels without photosensitivity.

Answer 68

(C) Porphyria Cutanea Tarda Porphyria Cutanea Tarda (PCT) is associated with photosensitivity, blistering skin lesions, and increased uroporphyrin in urine, often triggered by hepatitis C, alcohol, or estrogen.

Answer 69

(D) Ferrochelatase Deficiency in ferrochelatase causes Erythropoietic Protoporphyria (EPP), presenting with painful erythema and swelling after sun exposure and increased protoporphyrin levels in erythrocytes.

Answer 70

(D) Barbiturate use Barbiturates can induce cytochrome P450 enzymes, increasing heme demand and triggering acute attacks in Acute Intermittent Porphyria (AIP) patients.

Answer 71

(D) Coproporphyrinogen oxidase Deficiency of coproporphyrinogen oxidase causes Hereditary Coproporphyria (HCP), which can present with both abdominal pain and increased levels of coproporphyrin in the urine and feces.

Answer 72

Aldose reductase converts glucose to sorbitol in the polyol pathway.

Answer 73

Sorbitol is osmotically active and poorly permeable to cell membranes, leading to * osmotic stress * oxidative damage in tissues, such as the lens of the eye, nerves, and kidneys.

Answer 74

Cataracts are associated with sorbitol accumulation in the lens, leading to lens opacity and vision changes.

Answer 75

The polyol pathway depletes NADPH, which is necessary for regenerating reduced glutathione, an important antioxidant. This increases susceptibility to oxidative damage.

Answer 76

Aldose reductase inhibitors aim to reduce sorbitol accumulation and prevent complications like neuropathy and cataracts, but their clinical use is limited.

Answer 77

Tissues with insulin-independent glucose uptake: * lens of the eye * nerves * kidneys

Answer 78

The four major mechanisms are: * Polyol pathway flux * Advanced glycation end products (AGEs) formation * Protein kinase C (PKC) activation * Hexosamine pathway flux

Answer 79

* Increase vascular permeability * Promote inflammation * Enhance the production of extracellular matrix (ECM) proteins * Reduce nitric oxide (NO) production Leading to endothelial dysfunction. Contributes to: * Retinopathy * Nephropathy * Atherosclerosis

Answer 80

* Production of **UDP-N-acetylglucosamine (UDP-GlcNAc)** that modify proteins involved to signaling, transcription and metabolism * Impairming insulin signaling * Altering **gene expression** involved in i**nflammation and fibrosis** * Insulin **resistance** * Vascular and tissue damage leading to **cardiovascular disease and nephropathy**

Answer 81

Polyol pathway deplet NADPH ⇢ ⬇︎availability of NADPH to regenerate reduced glutathione (GSH) (antioxidant) ⇢ ⬆︎oxidative stress, contributing to complications such as neuropathy and cataracts.

Answer 82

Sorbitol accumulation in nerves: * osmotic stress * oxidative stress

Answer 83

Diabetic patients have elevated blood glucose levels, which increases sorbitol production by aldose reductase in the lens, leading to osmotic stress and lens opacity (cataracts).

Answer 84

Hexokinase converts glucose to glucose-6-phosphate in glycolysis; it has a low Km (high affinity for glucose) and functions efficiently at normal glucose levels, whereas aldose reductase is primarily active in hyperglycemic states.

Answer 85

The polyol pathway becomes more active, converting glucose to sorbitol (via aldose reductase) and then to fructose (via sorbitol dehydrogenase).

Answer 86

Answer: (B) Oxidative damage due to elevated sorbitol levels In diabetic cataracts, hyperglycemia leads to excess glucose conversion to sorbitol by aldose reductase. Sorbitol accumulation causes osmotic and oxidative stress, resulting in lens opacities.

Answer 87

Answer: (B) Aldose reductase Aldose reductase converts glucose to sorbitol in hyperglycemic states. Sorbitol accumulation in peripheral nerves causes osmotic stress and contributes to diabetic neuropathy, presenting with numbness and tingling.

Answer 88

Answer: (B) Sorbitol accumulation causing osmotic stress in renal cells Aldose reductase converts excess glucose to sorbitol in hyperglycemic conditions. Sorbitol accumulates in renal cells, causing osmotic damage and contributing to diabetic nephropathy.

Answer 89

Answer: (B) Inhibition of aldose reductase Aldose reductase inhibitors could prevent further sorbitol accumulation in the lens and reduce the risk of developing cataracts and other microvascular complications in diabetes.

Answer 90

Answer: (A) Increased oxidative stress from sorbitol accumulation in Schwann cells Sorbitol accumulation in Schwann cells due to aldose reductase activity causes osmotic and oxidative stress, leading to diabetic peripheral neuropathy.

Answer 91

Transcription factor that regulates the expression of genes involved: * Cell cycle arrest * DNA repair * Apoptosis Prevent tumor development

Answer 92

Prevents the accumulation of mutations by * arresting the cell cycle * promoting DNA repair * inducing apoptosis in response to cellular stress.

Answer 93

**Acquired mutations** that lead to **loss of function** of the p53 protein are the most common mutations in human cancers, occurring in more than 50% of all cases.

Answer 94

Autosomal dominant familial cancer syndrome caused by a germline mutation in the p53 gene, resulting in a high risk of multiple cancers at a young age.

Answer 95

* Cell cycle arrest (via p21) * DNA repair (via GADD45) * Apoptosis (via BAX, PUMA, NOXA)

Answer 96

Upregulation of p21⇢ Inhibition of CDK ⇢ Inhibition of phosphorilation of Rb protein ⇢ inhibition of release of E2F E2F is essential to entering into S phase

Answer 97

Controlling p53 levels under normal condition: MDM2 is an E3 ubiquitin ligase that binds to p53 and targets it for degradation via the ubiquitin-proteasome pathway

Answer 98

* Failure to regulate the cell cycle * Impaired DNA repair * Reduced apoptosis Increased risk of tumor formation due to unchecked cell proliferation.

Answer 99

* DNA damage (e.g., radiation, UV light) * Oncogene activation (e.g., Ras, Myc) * Hypoxia * Telomere shortening

Answer 100

Loss of heterozygosity (LOH) occurs when one allele of the p53 gene is deleted and the other is mutated, resulting in a complete loss of p53 function in many tumors.

Answer 101

Upregulating pro-apoptotic genes like BAX, PUMA, and NOXA, which lead to mitochondrial membrane permeabilization and activation of the apoptotic cascade.

Answer 102

* Poor prognosis * Guide therapeutic decisions, such as the use of specific chemotherapies or targeted therapies.

Answer 103

p53 primarily controls the G1/S checkpoint to prevent the replication of damaged DNA.

Answer 104

p53 prevents tumor formation by ensuring that cells with damaged DNA do not proliferate, either by arresting the cell cycle for repair or by inducing apoptosis if the damage is irreparable.

Answer 105

Answer: (C) Induction of cell cycle arrest at the G1/S checkpoint to allow DNA repair p53 induces cell cycle arrest at the G1/S checkpoint by upregulating p21, allowing time for DNA repair before replication proceeds. This mechanism prevents the proliferation of damaged cells, reducing the risk of tumor formation.

Answer 106

Answer: (B) Impaired induction of p21, resulting in uncontrolled progression through the G1/S checkpoint Loss of p53 function leads to a failure to induce p21, which is critical for inhibiting CDKs and halting cell cycle progression at the G1/S checkpoint. Without p21, cells with damaged DNA continue to divide, contributing to tumorigenesis.

Answer 107

Answer: (B) Enhanced degradation of p53, leading to reduced transcription of pro-apoptotic genes MDM2 is a negative regulator of p53; increased MDM2 expression promotes ubiquitin-mediated degradation of p53, reducing its levels and impairing its ability to activate pro-apoptotic genes.

Answer 108

Answer: (C) p21 (CDKN1A) p21 is a direct target of p53 and is crucial for cell cycle arrest in response to DNA damage. A mutation in p53 that prevents it from binding DNA would result in decreased p21 expression.

Answer 109

Answer: (B) Upregulation of pro-apoptotic genes like BAX and PUMA, leading to mitochondrial membrane permeabilization p53 promotes apoptosis by upregulating pro-apoptotic genes such as BAX and PUMA, which increase mitochondrial membrane permeability, leading to the release of cytochrome c and activation of the intrinsic apoptotic pathway.

Answer 110

HLA-DQ2 HLA-DQ8

Answer 111

HLA-DR3 HLA-DR4

Answer 112

HLA-DR2 HLA-DR3

Answer 113

Resistance is due to the modification of the peptidoglycan precursor from D-Ala-D-Ala to D-Ala-D-Lac or D-Ala-D-Ser, reducing vancomycin binding.

Answer 114

The van genes (e.g., vanA, vanB) encode proteins that alter the terminal amino acids in the cell wall precursors.

Answer 115

Vancomycin binds to the D-Ala-D-Ala terminus of peptidoglycan precursors, preventing their incorporation into the cell wall and inhibiting cell wall synthesis.

Answer 116

β-lactamases hydrolyze the β-lactam ring of penicillins, cephalosporins, and other β-lactam antibiotics, rendering them inactive.

Answer 117

Mutations in DNA gyrase or topoisomerase IV, reducing drug binding to these enzymes.

Answer 118

Efflux pumps actively transport antibiotics out of bacterial cells, decreasing intracellular drug concentration and efficacy.

Answer 119

Methylation of 23S rRNA at the ribosome binding site prevents macrolides from binding effectively to the bacterial ribosome.

Answer 120

Reduce their affinity for β-lactam antibiotics, as seen in methicillin-resistant Staphylococcus aureus (MRSA).

Answer 121

Linezolid Daptomycin Tigecycline Quinupristin/dalfopristin.

Answer 122

Plasmids and transposons often carry resistance genes (e.g., van genes) that can be transferred between bacteria, spreading resistance.

Answer 123

Hospitalized patients, especially those with prolonged antibiotic use, are at high risk for VRE infections.

Answer 124

* Hand hygiene * Contact precautions * Antibiotic stewardship

Answer 125

Porin mutations decrease the permeability of the bacterial outer membrane, reducing antibiotic uptake.

Answer 126

Vancomycin resistance leads to continued peptidoglycan synthesis despite the presence of the antibiotic, maintaining cell wall integrity.

Answer 127

* Selecting appropriate antibiotics * Managing resistant infections effectively.

Answer 128

Answer: (B) Substitution of D-alanine with D-lactate in the peptidoglycan precursor Vancomycin-resistant Enterococcus (VRE) resists vancomycin by substituting D-alanine with D-lactate or D-serine in its peptidoglycan precursor, which prevents vancomycin from binding effectively to the target

Answer 129

Answer: (E) Mutation in penicillin-binding proteins (PBPs) MRSA resists β-lactam antibiotics primarily through a mutation in the penicillin-binding proteins (PBPs), particularly PBP2a, which has a low affinity for β-lactams.

Answer 130

Answer: (B) vanA gene The vanA gene is responsible for vancomycin resistance in Enterococcus faecium by encoding enzymes that alter the terminal D-Ala-D-Ala to D-Ala-D-Lac.

Answer 131

Answer: (B) Daptomycin depolarizes the bacterial cell membrane, causing rapid cell death. Daptomycin works by binding to bacterial cell membranes and causing depolarization, which leads to the loss of membrane potential and cell death.

Answer 132

Answer: (B) Substitution of D-alanine with D-serine or D-lactate VRE achieves resistance to vancomycin by substituting the terminal D-alanine in its peptidoglycan precursors with either D-serine or D-lactate, reducing vancomycin binding affinity.

Answer 133

A subtype of Primary Ciliary Dyskinesia (PCD) characterized by the triad of recurrent sinusitis, bronchiectasis, and situs inversus (e.g., dextrocardia).

Answer 134

Genetic mutations that result in defective ciliary structure or function, leading to impaired mucociliary clearance.

Answer 135

DNAI1 and DNAH5, which encode proteins crucial for ciliary function.

Answer 136

The triad of recurrent sinusitis, bronchiectasis, and situs inversus totalis (mirror image reversal of thoracic and abdominal organs).

Answer 137

Infertility in males is due to immotile or dysfunctional sperm (defective flagella). In females, impaired ciliary function in the fallopian tubes can reduce fertility or cause ectopic pregnancies.

Answer 138

* Nasal nitric oxide test (low levels) * High-speed video microscopy (abnormal ciliary beat) * Genetic testing * Electron microscopy (revealing ciliary defects).

Answer 139

Situs inversus refers to the mirror-image reversal of internal organs, such as the heart on the right side (dextrocardia) and abdominal organs reversed.

Answer 140

* Airway clearance techniques (e.g., chest physiotherapy) * Antibiotics for infections * Supportive care (e.g., bronchodilators, management of hearing loss).

Answer 141

* Chronic respiratory issues such as bronchiectasis * Hearing loss from recurrent otitis media * Potential fertility problems.

Answer 142

Cilia are hair-like structures that move mucus and fluids; in PCD, ciliary dysfunction leads to poor mucus clearance and recurrent infections.

Answer 143

Defective ciliary function impairs mucociliary clearance, leading to mucus stasis and recurrent infections like sinusitis and bronchitis.

Answer 144

Answer: (B) Ciliary dysfunction due to dynein arm defects The patient’s symptoms (chronic cough, recurrent pneumonia, otitis media, bronchiectasis, and situs inversus) suggest Kartagener Syndrome, a subtype of Primary Ciliary Dyskinesia (PCD) caused by dynein arm defects.

Answer 145

Answer: (C) Absent or dysfunctional dynein arms in the sperm flagella Infertility in males with Kartagener Syndrome is due to defective ciliary function in the sperm flagella, leading to reduced sperm motility

Answer 146

Answer: (B) Measurement of nasal nitric oxide levels Low nasal nitric oxide levels are characteristic of PCD and are used as a diagnostic test to support the diagnosis.

Answer 147

Answer: (B) Presence of Kartagener Syndrome triad The patient’s presentation suggests Kartagener Syndrome, which includes the triad of recurrent sinusitis, bronchiectasis, and situs inversus.

Answer 148

Answer: (B) Defective ciliary motility in the fallopian tubes Infertility in females with Kartagener Syndrome is typically due to defective ciliary motility in the fallopian tubes, which affects the transport of the ovum.

Answer 149

Ornithine Transcarbamylase (OTC) Deficiency.

Answer 150

X-linked recessive.

Answer 151

Ornithine Transcarbamylase (OTC) catalyzes the conversion of carbamoyl phosphate and ornithine to citrulline in the urea cycle.

Answer 152

* Elevated plasma ammonia * Low blood urea nitrogen (BUN) * Elevated orotic acid in urine * Low or absent plasma citrulline.

Answer 153

Due to excess carbamoyl phosphate being diverted into the pyrimidine synthesis pathway, leading to increased orotic acid production.

Answer 154

* Poor feeding * Vomiting * Lethargy * Hypotonia (decreased muscle tone) * Seizures * Hyperammonemic encephalopathy.

Answer 155

* Hemodialysis to rapidly reduce ammonia levels * Ammonia scavenger drugs (e.g., sodium phenylacetate, sodium benzoate) * Intravenous glucose and lipids to prevent catabolism.

Answer 156

* Low-protein diet * Ammonia scavenger medications (e.g., sodium phenylbutyrate) * Essential amino acid supplementation * Consideration of liver transplantation in severe cases.

Answer 157

* Elevated orotic acid in urine * Low or absent citrulline in plasma

Answer 158

Because urea synthesis is impaired due to the enzyme defect in the urea cycle.

Answer 159

* High protein intake * Illness * Fasting

Answer 160

"OTC: Out of The Citrulline" O: Orotic aciduria (elevated orotic acid in urine) T: Toxic Ammonia (hyperammonemia) C: Citrulline Low (low or absent plasma citrulline)

Answer 161

L-arginine provides substrates to enhance residual urea cycle function and helps promote the excretion of nitrogen.

Answer 162

Because it is an X-linked recessive disorder, and males have only one X chromosome, making them more likely to express the disease.

Answer 163

Hyperammonemia due to impaired conversion of ammonia to urea.

Answer 164

Answer: (D) Ornithine transcarbamylase (OTC) deficiency The infant presents with symptoms of hyperammonemia, poor feeding, seizures, and elevated orotic acid, which is characteristic of OTC deficiency, a urea cycle disorder.

Answer 165

Answer: (B) X-linked recessive mutation in the OTC gene OTC deficiency is inherited in an X-linked recessive pattern, making this the most likely genetic finding in a patient with hyperammonemia and elevated orotic acid.

Answer 166

Answer: (B) Ornithine transcarbamylase (OTC) The elevated ammonia, low BUN, and increased orotic acid are specific for OTC deficiency, where the enzyme ornithine transcarbamylase is deficient.

Answer 167

Answer: (D) Low-protein diet A low-protein diet is essential in managing OTC deficiency to reduce the production of ammonia from the breakdown of dietary proteins

Answer 168

Answer: (A) Sodium phenylbutyrate Sodium phenylbutyrate is an ammonia scavenger used to reduce elevated ammonia levels in urea cycle disorders, including OTC deficiency.

Answer 169

Indirect bilirubin is lipid-soluble and transported bound to albumin; it is converted in the liver to direct bilirubin, which is water-soluble and excreted in bile.

Answer 170

Because it is lipid-soluble and bound to albumin, making it unable to pass through the kidneys.

Answer 171

Conjugated (direct) bilirubin is elevated due to impaired excretion from bile duct obstruction.

Answer 172

UDP-glucuronyl transferase deficiency.

Answer 173

Elevated conjugated bilirubin, elevated alkaline phosphatase (ALP), and mildly elevated AST and ALT.

Answer 174

Ultrasound, MRCP (Magnetic Resonance Cholangiopancreatography), and ERCP (Endoscopic Retrograde Cholangiopancreatography).

Answer 175

A: Dark urine is due to the excretion of conjugated bilirubin in the urine; pale stools result from the lack of bilirubin in the intestines.

Answer 176

A: PSC is an autoimmune, inflammatory disease causing fibrosis and strictures of the bile ducts, leading to cholestasis.

Answer 177

A: Primary Biliary Cholangitis (PBC).

Answer 178

A: Scleral icterus (yellowing of the whites of the eyes) and generalized itching due to bile salt accumulation.

Answer 179

A: Biliary atresia.

Answer 180

A: Clonorchiasis (caused by the liver fluke Clonorchis sinensis)

Answer 181

A: Jaundice, pruritus (itching), dark urine, pale stools, and potentially abdominal pain.

Answer 182

A: By obstructing the bile ducts, preventing bile from reaching the intestines.

Answer 183

A: A lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase), leading to glycogen accumulation in various tissues, especially cardiac and skeletal muscles

Answer 184

A: Acid alpha-glucosidase (acid maltase).

Answer 185

A: Autosomal recessive.

Answer 186

* Hypotonia * Generalized muscle weakness * Cardiomegaly * Hypertrophic cardiomyopathy * Respiratory distress * Feeding difficulties * Failure to thrive.

Answer 187

* Progressive muscle weakness (especially proximal muscles) * Respiratory insufficiency * Milder or no cardiac involvement.

Answer 188

A: Enzyme assay showing low acid alpha-glucosidase activity in blood, skin fibroblasts, or muscle biopsy.

Answer 189

A: Mutations in the GAA gene on chromosome 17.

Answer 190

A: Enzyme Replacement Therapy (ERT) with alglucosidase alfa.

Answer 191

A: Due to glycogen accumulation in the cardiac muscle cells, leading to hypertrophic cardiomyopathy.

Answer 192

A: Vacuoles filled with glycogen in muscle tissue.

Answer 193

"Pompe Trashes the Pump" P: Progressive muscle weakness O: Organomegaly (hepatomegaly, cardiomegaly) M: Myopathy (skeletal muscle weakness) P: Pulmonary issues (respiratory distress) E: Exercise intolerance E: Enlargement tongue

Answer 194

A: Poor prognosis, with death usually occurring within the first year of life due to cardiorespiratory failure

Answer 195

A: Cardiac, skeletal, and smooth muscles

Answer 196

A: Confirms mutations in the GAA gene and assists with genetic counseling for families.

Answer 197

A: ERT provides a recombinant form of acid alpha-glucosidase, reducing glycogen accumulation, improving muscle function, and prolonging survival.

Answer 198

Answer: (B) Acid alpha-glucosidase The patient presents with hypotonia, difficulty feeding, respiratory distress, and cardiomegaly, which are characteristic of Pompe disease. This condition is due to a deficiency of acid alpha-glucosidase, leading to glycogen accumulation in muscles

Answer 199

Answer: (C) Pompe disease (Glycogen Storage Disease Type II) The autopsy findings of glycogen accumulation in lysosomes of cardiac and skeletal muscle cells are classic for Pompe disease

Answer 200

Answer: (B) Enzyme replacement therapy (ERT) ERT with recombinant acid alpha-glucosidase is the main treatment for Pompe disease. It helps reduce glycogen accumulation, improve muscle function, and prolong survival.

Answer 201

Answer: (B) Enzyme assay for acid alpha-glucosidase activity Measuring acid alpha-glucosidase activity in blood, skin fibroblasts, or muscle biopsy is the key diagnostic test for confirming Pompe disease.

Answer 202

Answer: (B) Replacement of deficient acid alpha-glucosidase to break down glycogen in lysosomes Enzyme replacement therapy provides the deficient enzyme (acid alpha-glucosidase) to break down glycogen in lysosomes, reducing accumulation and improving symptoms.

Answer 203

A: To convert glucose to glucose-6-phosphate after a meal, helping to regulate blood glucose levels by storing or using excess glucose.

Answer 204

A: In the liver and pancreatic beta cells

Answer 205

A: It indicates a low affinity for glucose, meaning glucokinase becomes active only when glucose concentrations are high, such as after a carbohydrate-rich meal.

Answer 206

A: To allow the liver to continuously take up and phosphorylate glucose even when glucose-6-phosphate levels are high.

Answer 207

A: It allows the liver to rapidly convert large amounts of glucose to glucose-6-phosphate, efficiently handling high glucose levels after a meal.

Answer 208

A: To convert glucose to glucose-6-phosphate in most tissues, providing a steady supply for energy production and biosynthesis.

Answer 209

A: Low Km (high affinity for glucose), low Vmax, and inhibited by glucose-6-phosphate.

Answer 210

A: To prevent excessive accumulation of glucose-6-phosphate in peripheral tissues, ensuring balance and efficient use of glucose.

Answer 211

A: By converting excess glucose to glucose-6-phosphate, which is then stored as glycogen or used in other metabolic pathways.

Answer 212

A: It allows the liver to take up large amounts of glucose from the blood after a meal, reducing blood glucose levels.

Answer 213

A: Acts as a glucose sensor to help regulate insulin secretion in response to blood glucose levels.

Answer 214

A: Glucokinase has a low affinity for glucose (high Km), while hexokinase has a high affinity for glucose (low Km).

Answer 215

A: Because its high Km makes it more active at high glucose concentrations, allowing it to manage large amounts of glucose efficiently.

Answer 216

A: Hexokinase, due to its low Km (high affinity for glucose).

Answer 217

A: "Glucokinase Goes for Glucose in Great amounts!"

Answer 218

Answer: (B) Glucokinase Glucokinase is upregulated to increase glucose uptake and storage as glycogen in the liver after a meal, particularly in response to high glucose levels.

Answer 219

Answer: (B) Glucokinase The enzyme described has a high Km (low affinity for glucose) and is not inhibited by glucose-6-phosphate, characteristics specific to glucokinase.

Answer 220

Answer: (B) Glucokinase After a carbohydrate-rich meal, glucokinase in the liver becomes most active to phosphorylate and store excess glucose, lowering blood glucose levels.

Answer 221

Answer: (C) Promotes glycogen synthesis in the liver after a meal The described enzyme is glucokinase, which is highly active in the liver after a meal to promote glycogen synthesis and reduce blood glucose.

Answer 222

Answer: (A) Hyperglycemia after meals A mutation in glucokinase affects glucose uptake and phosphorylation in the liver and pancreatic beta cells, leading to postprandial hyperglycemia.

Answer 223

Mutations in the PKD1 gene (on chromosome 16) or PKD2 gene (on chromosome 4).

Answer 224

* Hematuria * Flank or back pain * Hypertension * Progressive renal insufficiency * Enlarged kidneys with multiple cysts.

Answer 225

Berry aneurysm (saccular aneurysm) in the circle of Willis, which can lead to subarachnoid hemorrhage.

Answer 226

Hepatic cysts, mitral valve prolapse, colonic diverticula, and pancreatic cysts

Answer 227

Ultrasound to detect multiple renal cysts.

Answer 228

Autosomal dominant.

Answer 229

Progressive cyst formation and enlargement cause kidney tissue destruction and loss of function, leading to chronic kidney disease and potentially end-stage renal disease (ESRD).

Answer 230

Blood pressure control (ACE inhibitors/ARBs), pain management, monitoring for aneurysms, and management of chronic kidney disease (e.g., dialysis, kidney transplantation).

Answer 231

Cysts can become infected, leading to recurrent UTIs.

Answer 232

ADPKD typically presents in adulthood with multiple large cysts and systemic manifestations, whereas ARPKD presents in infancy or early childhood with enlarged kidneys and hepatic fibrosis.

Answer 233

Answer: (A) Mutation in the PKD1 gene on chromosome 16 Explanation: ADPKD is most commonly caused by a mutation in the PKD1 gene on chromosome 16 (about 85% of cases). The PKD2 gene mutation on chromosome 4 accounts for 15% of cases. COL1A1 is associated with osteogenesis imperfecta, HNF1B with renal cysts and diabetes syndrome, and TSC1 with tuberous sclerosis.

Answer 234

Answer: (B) CT angiography of the head Explanation: The patient's sudden severe headache and neck stiffness suggest a possible subarachnoid hemorrhage, which is a known complication of ADPKD due to the risk of Berry aneurysm rupture. CT angiography of the head is the most appropriate initial test to assess for an aneurysm or hemorrhage.

Answer 235

Answer: (C) Angiotensin-converting enzyme inhibitors (ACE inhibitors) Explanation: ACE inhibitors are preferred in managing hypertension in ADPKD patients because they reduce intraglomerular pressure and slow the progression of kidney disease by blocking the effects of angiotensin II, which is especially beneficial in maintaining kidney function.

Answer 236

Answer: (B) Polycystic liver disease Explanation: Polycystic liver disease is a common extrarenal manifestation of ADPKD, characterized by multiple liver cysts. This condition is generally asymptomatic and does not usually affect liver function.

Answer 237

Answer: (D) Kidney transplantation Explanation: Kidney transplantation is the definitive treatment for end-stage renal disease (ESRD) in patients with ADPKD. While dialysis can be used as a bridge to transplantation, it is not a definitive cure. Other options (angioplasty, renal artery stenting, and nephrolithotomy) do not address the underlying kidney failure.

Answer 238

Cystathionine β-synthase (CBS) deficiency.

Answer 239

**HOMOCYSTIN**uria **H**omocyteine in urine **O**cular chages (lens dislocation downward and inward) **M**arfanoid habitus (tall stature, arachnodactyly) **O**steoporosis **C**ardiovascular issues (MI and stroke) k**Y**phosis **S**kin hiperpigmentation **T**hrombosis **IN**tellectual disability

Answer 240

**HOMOCYSTIN**uria **N**itroprusside cyanide test.

Answer 241

Vitamin B6 (pyridoxine), Vitamin B12 (cobalamin), and Folic acid.

Answer 242

Autosomal recessive.

Answer 243

Low methionine diet with cysteine supplementation.

Answer 244

In homocystinuria, the lens dislocation is downward, while in Marfan syndrome, it is upward.

Answer 245

Elevated homocysteine levels cause endothelial damage and promote coagulation.

Answer 246

Betaine acts as an alternative methyl donor to convert homocysteine to methionine.

Answer 247

It can lead to elevated homocysteine levels due to impaired remethylation of homocysteine to methionine.

Answer 248

A: Facilitates basal glucose uptake; found in most tissues, especially the brain and red blood cells (RBCs).

Answer 249

A: GLUT 4.

Answer 250

A: GLUT 2 allows glucose entry into pancreatic β cells; glucose metabolism raises ATP levels, leading to insulin release.

Answer 251

A: Found primarily in neurons; ensures constant glucose supply to the brain.

Answer 252

A: GLUT 5.

Answer 253

A: GLUT 2.

Answer 254

A: GLUT 4 is translocated to the cell surface of muscle and adipose cells, facilitating glucose uptake.

Answer 255

A: Ensures a continuous supply of glucose for energy, as RBCs rely exclusively on glycolysis.

Answer 256

A: GLUT 4 in muscle and adipose tissue.

Answer 257

Decreased affinity of hemoglobin for oxygen, promoting oxygen release to tissues.

Answer 258

* Increased 2,3-BPG * Increased CO₂ * Decreased pH * Increased temperature.

Answer 259

Increased affinity of hemoglobin for oxygen, promoting oxygen binding in the lungs.

Answer 260

*Decreased 2,3-BPG * Decreased CO₂ * Increased pH * Decreased temperature.

Answer 261

2,3-BPG binds to deoxygenated hemoglobin, stabilizing the T state and decreasing oxygen affinity.

Answer 262

The effect of pH and CO₂ on hemoglobin's oxygen affinity; decreased pH and increased CO₂ cause a rightward shift in the curve.

Answer 263

CO binds tightly to hemoglobin, forming carboxyhemoglobin, which increases oxygen affinity (leftward shift) but prevents oxygen release

Answer 264

It reflects cooperative binding: hemoglobin's affinity for oxygen increases as more oxygen molecules bind.

Answer 265

It promotes oxygen unloading to active tissues with high metabolic demand.

Answer 266

Increased 2,3-BPG production causes a rightward shift, facilitating oxygen release to tissues.

Answer 267

Answer: (C) Increased levels of 2,3-bisphosphoglycerate (2,3-BPG) Explanation: At high altitudes, the body compensates for lower oxygen availability by increasing 2,3-BPG levels, which shifts the oxygen-hemoglobin dissociation curve to the right, promoting oxygen release to tissues.

Answer 268

Answer: (A) Decreased affinity due to rightward shift Explanation: A low pH and elevated pCO₂ cause a rightward shift in the oxygen-hemoglobin dissociation curve (Bohr effect), decreasing hemoglobin's oxygen affinity and promoting oxygen release to tissues.

Answer 269

Answer: (B) Leftward shift with decreased oxygen release Explanation: Carbon monoxide (CO) binds tightly to hemoglobin, forming carboxyhemoglobin, which increases hemoglobin's affinity for oxygen (leftward shift) but prevents oxygen release to tissues, causing hypoxia.

Answer 270

Answer: (C) Decreased oxygen release, leftward shift Explanation: In carbon monoxide poisoning, CO binds to hemoglobin, causing a leftward shift of the oxygen-hemoglobin dissociation curve, which increases oxygen binding but reduces oxygen release to tissues.

Answer 271

Answer: (D) Leftward shift due to decreased pCO₂ Explanation: Mechanical ventilation with 100% oxygen will lead to decreased pCO₂ and increased pH, causing a leftward shift in the oxygen-hemoglobin dissociation curve, which increases hemoglobin's affinity for oxygen.

Answer 272

To generate NADPH in the pentose phosphate pathway (PPP), protecting cells, especially red blood cells, from oxidative damage.

Answer 273

A: Presence of Heinz bodies (denatured hemoglobin) and bite cells (RBCs with pieces removed by splenic macrophages).

Answer 274

A: Infections, certain medications (e.g., sulfa drugs, antimalarials, NSAIDs), and foods like fava beans.

Answer 275

A: Because G6PD deficiency is an X-linked recessive disorder; males have only one X chromosome, so one defective gene results in the condition.

Answer 276

Enzyme assay in red blood cells ## Footnote (performed several weeks after a hemolytic episode).

Answer 277

Creating an unfavorable environment for the malaria parasite within red blood cells, reducing its survival.

Answer 278

A: Fatigue, jaundice, dark urine, pallor, back pain, and splenomegaly.

Answer 279

A: NADPH maintains glutathione in its reduced form, which detoxifies reactive oxygen species and protects RBCs from oxidative damage.

Answer 280

A: Common in African, Mediterranean, Middle Eastern, and South Asian populations due to the selective advantage against malaria.

Answer 281

A: Avoid triggers (oxidative stressors like certain drugs, foods) and provide supportive care (hydration, oxygen, transfusion if severe) during hemolytic episodes.

Answer 282

A: To regulate calcium and phosphate levels in the blood by acting on the bones, kidneys, and intestines.

Answer 283

PTH increases **bone resorption** by stimulating osteoclast activity, indirectly leading to the **release of calcium and phosphate** into the bloodstream.

Answer 284

PTH **increases** **calcium reabsorption** in the distal convoluted tubules and **decreases phosphate reabsorption** in the proximal convoluted tubules.

Answer 285

A: PTH stimulates the production of 1,25-dihydroxyvitamin D (calcitriol) in the kidneys, which enhances calcium absorption in the intestines.

Answer 286

A: PTH reduces phosphate reabsorption in the kidneys, promoting phosphate excretion and preventing hyperphosphatemia.

Answer 287

A: High serum calcium levels inhibit PTH secretion, while low serum calcium levels stimulate PTH secretion.

Answer 288

"Stones, thrones, bones, groans, and psychiatric overtones" * Renal stones (stones) * Polyuria (thrones) * Osteoporosis and pain (bones) * Constipation (groans) * Neuropsychiatric disturbances (psychiatric overtones)

Answer 289

A: Multiple Endocrine Neoplasia (MEN) types 1 and 2A.

Answer 290

A: 1α-hydroxylase, which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol).

Answer 291

A: Hypocalcemia, tetany, and hyperphosphatemia.

Answer 292

A: Wilms tumor (Nephroblastoma).

Answer 293

A: Typically in children under 5 years old, with a peak incidence between ages 2-4.

Answer 294

A: WT1 gene mutations/deletions on chromosome 11p13 and WT2 gene abnormalities on chromosome 11p15.

Answer 295

A: Wilms tumor, Aniridia, Genitourinary anomalies, and intellectual Retardation

Answer 296

A: Deletion on chromosome 11p13 affecting the WT1 and PAX6 genes.

Answer 297

A: Wilms tumor, diffuse mesangial sclerosis (nephropathy), and gonadal dysgenesis.

Answer 298

WT1 gene mutation on chromosome 11p13.

Answer 299

* Hemihyperplasia * Macroglossia * Macrosomia * Omphalocele * Increased risk of Wilms tumor.

Answer 300

A: Abnormalities on chromosome 11p15.5, including paternal uniparental disomy (UPD), loss of imprinting, or mutations affecting IGF2 and H19 genes.

Answer 301

A: Abdominal ultrasounds every 3 months until age 8 for Wilms tumor; alpha-fetoprotein (AFP) monitoring every 3 months until age 4 for hepatoblastoma.

Answer 302

A: A large, solitary, well-circumscribed mass often with areas of hemorrhage, necrosis, or cystic degeneration.

Answer 303

A: A triphasic pattern consisting of blastemal, stromal, and epithelial cell types.

Answer 304

A: Surgery (nephrectomy), chemotherapy, and radiation therapy for advanced stages or unfavorable histology.

Answer 305

A: Beckwith-Wiedemann syndrome.

Answer 306

A: The WT1 gene is a tumor suppressor gene involved in kidney and gonadal development. Mutations or deletions lead to an increased risk of Wilms tumor.

Answer 307

A: Favorable histology has a high cure rate (>90%), while unfavorable histology (anaplastic) has a poorer prognosis.

Answer 308

A: The lungs are the most common site of metastasis for Wilms tumor.

Answer 309

A: The PAX6 gene is crucial for eye development. Its deletion results in aniridia (absence of the iris), a key feature of WAGR syndrome.

Answer 310

A: Due to the high risk of developing bilateral Wilms tumor

Answer 311

A: Wilms tumor often presents as a unilateral renal mass that does not cross the midline, while neuroblastoma often arises from the adrenal gland and may cross the midline.

Answer 312

A: Vitamin A deficiency

Answer 313

A: Rickets – characterized by bowed legs, rachitic rosary, and growth retardation.

Answer 314

A: Vitamin E deficiency.

Answer 315

A: Essential for the synthesis of clotting factors (II, VII, IX, X) and proteins C and S involved in coagulation.

Answer 316

A: Hemorrhagic disease of the newborn (bleeding due to reduced clotting factor synthesis).

Answer 317

A: Niacin (Vitamin B3) deficiency.

Answer 318

Scurvy – characterized by poor wound healing, gum bleeding, petechiae, and corkscrew hairs.

Answer 319

A: Thiamine (Vitamin B1) deficiency.

Answer 320

A: Vitamin B12 (cobalamin) deficiency.

Answer 321

A: Riboflavin (Vitamin B2) deficiency.

Answer 322

A: Megaloblastic anemia and risk of neural tube defects in pregnancy.

Answer 323

A: Osteomalacia.

Answer 324

A: Vitamin K deficiency.

Answer 325

A: Pyridoxine (Vitamin B6) deficiency.

Answer 326

A: Thiamine (Vitamin B1) deficiency; symptoms include neuropathy, muscle weakness, cardiac failure, and edema.

Answer 327

A: Lysosomes.

Answer 328

A: Deficiency or dysfunction of specific lysosomal enzymes, leading to the accumulation of undegraded substrates.

Answer 329

A: β-hexosaminidase A.

Answer 330

* Developmental delay * Seizures * Cherry-red spot on the retina * Progressive neurodegeneration.

Answer 331

A: Glucocerebrosidase.

Answer 332

* Hepatosplenomegaly * Bone pain * Anemia * Thrombocytopenia * "Gaucher cells" (lipid-laden macrophages).

Answer 333

A: Hunter syndrome (MPS II).

Answer 334

* Coarse facial features * Joint stiffness * Hepatosplenomegaly * Developmental delay.

Answer 335

A: Acid α-glucosidase (acid maltase).

Answer 336

A: Cardiomegaly, muscle weakness (hypotonia), respiratory distress, and hepatomegaly.

Answer 337

A: Metachromatic leukodystrophy.

Answer 338

A: Progressive neurodegeneration, peripheral neuropathy, ataxia, and developmental regression.

Answer 339

A: Niemann-Pick disease.

Answer 340

A: Hepatosplenomegaly, cherry-red spot on the retina, progressive neurodegeneration, and "foam cells" (lipid-laden macrophages).

Answer 341

A: Hurler syndrome involves corneal clouding and is more severe, whereas Hunter syndrome does not have corneal clouding and is X-linked recessive.

Answer 342

A: Enzyme activity assays in cultured fibroblasts or leukocytes.

Answer 343

A: Enzyme replacement therapy (ERT).

Answer 344

A: Due to defective transport or function of the enzymes within lysosomes, causing them to be released into the serum.

Answer 345

A: Autosomal recessive inheritance.

Answer 346

A: Absence of hepatosplenomegaly in Tay-Sachs disease.

Answer 347

Answer: B. Hexosaminidase A Explanation: The child likely has Tay-Sachs disease, characterized by a deficiency of hexosaminidase A, leading to the accumulation of GM2 ganglioside. The absence of hepatosplenomegaly helps differentiate it from Niemann-Pick disease.

Answer 348

Answer: B. Hunter syndrome Explanation: Hunter syndrome (MPS II) presents with the accumulation of heparan sulfate and dermatan sulfate, but without corneal clouding. It is X-linked and often involves aggressive behavior.

Answer 349

Answer: C. Sphingomyelinase Explanation: This is Niemann-Pick disease, characterized by sphingomyelinase deficiency, leading to sphingomyelin accumulation. The presence of hepatosplenomegaly differentiates it from Tay-Sachs disease.

Answer 350

Answer: B. Glucocerebroside Explanation: This is Gaucher disease, caused by a deficiency of glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages, giving them the "crumpled tissue paper" appearance.

Answer 351

Answer: A. Krabbe disease Explanation: Krabbe disease involves a deficiency of galactocerebrosidase, leading to galactocerebroside accumulation. It is characterized by peripheral neuropathy and optic atrophy.

Answer 352

Answer: B. α-L-iduronidase Explanation: This is Hurler syndrome (MPS I), caused by a deficiency in α-L-iduronidase. It leads to the accumulation of dermatan sulfate and heparan sulfate, with characteristic facial features and corneal clouding

Answer 353

Answer: B. Mannose-6-phosphate tagging in the Golgi apparatus Explanation: This describes I-cell disease, where there is defective mannose-6-phosphate tagging, preventing lysosomal enzymes from reaching the lysosome, leading to their secretion into the serum.

Answer 354

Answer: A. α-Galactosidase A Explanation: This is Fabry disease, an X-linked disorder caused by a deficiency of α-galactosidase A, leading to the accumulation of ceramide trihexoside

Answer 355

Answer: B. Arylsulfatase A Explanation: This is metachromatic leukodystrophy, caused by a deficiency in arylsulfatase A, leading to the accumulation of cerebroside sulfate

Answer 356

Answer: C. Acid α-glucosidase Explanation: This is Pompe disease (Type II glycogen storage disease), characterized by a deficiency in acid α-glucosidase, leading to glycogen accumulation in lysosomes.

Answer 357

Answer: C. Corneal clouding Explanation: Corneal clouding is a classic feature of Hurler syndrome, along with developmental delay and hepatosplenomegaly.

Answer 358

Answer: B. Defective enzyme targeting to the lysosome Explanation: In I-cell disease, defective mannose-6-phosphate tagging prevents enzymes from being directed to the lysosomes, leading to their secretion into the serum.

Answer 359

Answer: B. X-linked recessive Explanation: Hunter syndrome is an X-linked recessive disorder caused by a deficiency in iduronate-2-sulfatase.

Answer 360

Answer: B. α-L-iduronidase Explanation: Hurler syndrome is caused by a deficiency in α-L-iduronidase, leading to the accumulation of glycosaminoglycans such as dermatan sulfate and heparan sulfate.

Answer 361

Answer: C. Sphingomyelin Explanation: This is Niemann-Pick disease, characterized by the accumulation of sphingomyelin due to a deficiency in sphingomyelinase

Answer 362

Ankylosing spondylitis Reactive arthritis (Reiter’s syndrome) Psoriatic arthritis Inflammatory bowel disease (IBD)–associated arthritis

Answer 363

Multiple sclerosis Goodpasture syndrome Systemic lupus erythematosus (SLE)

Answer 364

Type 1 diabetes mellitus Graves' disease Hashimoto thyroiditis SLE Addison’s disease Pernicious anemia

Answer 365

Rheumatoid arthritis Type 1 diabetes mellitus Addison’s disease

Answer 366

Hashimoto thyroiditis Pernicious anemia

Answer 367

Celiac disease

Answer 368

Addison’s disease Myasthenia gravis Graves’ disease

Answer 369

Psoriasis (especially HLA-Cw6)

Answer 370

Infancy onset Severe hypoglycemia Hepatomegaly Lactic acidosis Hyperuricemia

Answer 371

Glucose-6-phosphatase

Answer 372

Glycogen Storage Disease Type I (Von Gierke)

Answer 373

Cardiomegaly Hypotonia Exercise intolerance Early death in severe form

Answer 374

Lysosomal α-1,4-glucosidase (acid maltase)

Answer 375

Glycogen Storage Disease Type II (Pompe)

Answer 376

Mild hypoglycemia Hepatomegaly Muscle Weakness Gluconeogenesis intact

Answer 377

Debranching enzyme (α-1,6-glucosidase)

Answer 378

Glycogen Storage Disease Type III (Cori)

Answer 379

Hepatosplenomegaly Cirrhosis Failure to thrive Muscule weakness

Answer 380

Branching enzyme (amylo-1,4-to-1,6 transglucosidase) Glycogen Storage Disease Type IV (Andersen)

Answer 381

Childhood to adolescence Muscle cramps Myoglobinuria with exercise Exercise intolerance

Answer 382

Muscle glycogen phosphorylase Glycogen Storage Disease Type V (McArdle)

Answer 383

Childhood Mild hypoglicemia Hepatomegaly Growth retardation

Answer 384

Liver glycogen phosphorylase Glycogen Storage Disease Type VI (Hers)

Answer 385

Answer: C) Pyruvate carboxylase Explanation: Pyruvate carboxylase catalyzes the first step in gluconeogenesis, converting pyruvate to oxaloacetate in the mitochondria. A deficiency in this enzyme leads to elevated levels of pyruvate, lactate, and alanine, as these substrates are diverted into other metabolic pathways, causing lactic acidosis and failure to thrive.

Answer 386

Answer: B) Lactate Explanation: During fasting or prolonged exercise, lactate, derived from anaerobic metabolism in muscles and red blood cells, is used by the liver for gluconeogenesis. Acetyl-CoA and ketone bodies cannot be used directly for glucose production, while even-chain fatty acids are not gluconeogenic.

Answer 387

Answer: B) Increased glycolysis due to elevated fructose 2,6-bisphosphate levels Explanation: Fructose 2,6-bisphosphate is a potent activator of phosphofructokinase-1 (PFK-1), which drives glycolysis. In insulin-deficient patients, fructose 2,6-bisphosphate levels can become dysregulated, leading to increased glycolysis despite hyperglycemia, worsening the metabolic disturbance.

Answer 388

Answer: D) Glucose-6-phosphatase Explanation: Glucose-6-phosphatase is responsible for converting glucose-6-phosphate into free glucose, which can be released into the bloodstream. A deficiency in this enzyme, as seen in glycogen storage diseases like Von Gierke disease, leads to hypoglycemia and glycogen accumulation in the liver.

Answer 389

Answer: C) Increased activity of fructose 1,6-bisphosphatase Explanation: Glucagon promotes gluconeogenesis by increasing the activity of fructose 1,6-bisphosphatase, which is responsible for the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate. This process favors glucose production during hypoglycemia.

Answer 390

Answer: D) Propionyl-CoA Explanation: Odd-chain fatty acids are metabolized to propionyl-CoA, which can then enter gluconeogenesis. A defect in the metabolism of odd-chain fatty acids would reduce the availability of propionyl-CoA, impairing gluconeogenesis from these fatty acids.

Answer 391

Answer: B) High levels of ATP Explanation: Pyruvate carboxylase is activated by high levels of acetyl-CoA, which signals that the TCA cycle is inhibited due to abundant ATP. This pushes pyruvate into gluconeogenesis rather than into the TCA cycle for energy production, promoting glucose synthesis.

Answer 392

The first step of gluconeogenesis is the conversion of pyruvate to oxaloacetate, catalyzed by pyruvate carboxylase. This step requires ATP and biotin as a cofactor.

Answer 393

Key substrates include: Lactate Alanine (via the alanine cycle) Glycerol (from triglycerides) Odd-chain fatty acids (converted to propionyl-CoA) Some amino acids (glucogenic)

Answer 394

High levels of fructose 2,6-bisphosphate activate phosphofructokinase-1 (PFK-1), promoting glycolysis. Low levels of fructose 2,6-bisphosphate activate fructose 1,6-bisphosphatase, promoting gluconeogenesis.

Answer 395

Glucose-6-phosphatase, found mainly in the liver and kidneys, is responsible for converting glucose-6-phosphate into glucose, which is released into the blood.

Answer 396

Acetyl-CoA is an allosteric activator of pyruvate carboxylase, signaling high energy levels and promoting gluconeogenesis by converting pyruvate into oxaloacetate.

Answer 397

Insulin increases the levels of fructose 2,6-bisphosphate, promoting glycolysis. Glucagon decreases the levels of fructose 2,6-bisphosphate, promoting gluconeogenesis

Answer 398

Back: Pyruvate can enter: TCA cycle (via acetyl-CoA) to generate ATP. Gluconeogenesis (via oxaloacetate) to synthesize glucose. The choice is regulated by the levels of acetyl-CoA and ATP. High ATP and acetyl-CoA promote gluconeogenesis.

Answer 399

Back: A deficiency in pyruvate carboxylase leads to the accumulation of pyruvate, which is converted into lactate and alanine, causing lactic acidosis and failure to thrive.

Answer 400

Back: Biotin is a cofactor for carboxylase enzymes, including pyruvate carboxylase, and is essential for adding CO₂ to pyruvate to form oxaloacetate in gluconeogenesis.

Answer 401

Back: Even-chain fatty acids cannot contribute to gluconeogenesis because they are metabolized entirely into acetyl-CoA, which cannot be converted back into glucose. Only odd-chain fatty acids can contribute via propionyl-CoA.

Answer 402

Back: Glycolysis breaks down glucose (6 carbons) into 2 molecules of pyruvate (3 carbons), generating 2 net ATP and 2 NADH molecules per glucose molecule. It occurs in the cytoplasm of all cells.

Answer 403

Back: Glucose → Glucose-6-Phosphate (Hexokinase/Glucokinase) Fructose-6-Phosphate → Fructose-1,6-Bisphosphate (Phosphofructokinase-1) Phosphoenolpyruvate → Pyruvate (Pyruvate Kinase)

Answer 404

Back: NADH is produced during glycolysis and carries electrons to the electron transport chain in mitochondria for ATP production in aerobic metabolism. In anaerobic conditions, NADH helps regenerate NAD⁺ by converting pyruvate into lactate.

Answer 405

Back: PFK-1 is the rate-limiting enzyme of glycolysis. It is activated by AMP and Fructose-2,6-Bisphosphate, and inhibited by ATP and Citrate (high-energy signals).

Answer 406

Fructose-2,6-bisphosphate is a key regulator that activates PFK-1 (stimulating glycolysis) and inhibits fructose-1,6-bisphosphatase (inhibiting gluconeogenesis).

Answer 407

Insulin dephosphorylates PFK-2, increasing fructose-2,6-bisphosphate levels, activating glycolysis. Glucagon phosphorylates PFK-2, reducing fructose-2,6-bisphosphate levels, favoring gluconeogenesis.

Answer 408

Hexokinase: Found in most tissues, has low Km (high affinity for glucose), inhibited by glucose-6-phosphate. Glucokinase: Found in liver/pancreas, high Km (low affinity, only active in high glucose), induced by insulin, inhibited by fructose-6-phosphate.

Answer 409

Pyruvate kinase deficiency impairs glycolysis, especially in red blood cells, leading to hemolytic anemia, splenomegaly, and a range of severity based on enzyme activity.

Answer 410

Back: In low oxygen conditions, pyruvate is converted to lactate to regenerate NAD⁺, which is required for glycolysis. This increases lactate production, leading to lactic acidosis (e.g., in sepsis, bowel ischemia, exercise).

Answer 411

Back: Aerobic: 30-32 ATP per glucose (with oxygen and mitochondria). Anaerobic: 2 ATP per glucose (without oxygen or mitochondria, producing lactate).

Answer 412

Back: In the alanine cycle, muscles break down protein, producing alanine, which is sent to the liver for conversion into glucose via gluconeogenesis. Alanine inhibits pyruvate kinase, slowing glycolysis in the liver.

Answer 413

2,3-BPG, produced from glycolysis in red blood cells, binds to hemoglobin and helps release oxygen to tissues, especially during hypoxia (e.g., at high altitudes).

Answer 414

Answer: C) TCA cycle Explanation: In intense exercise, the lack of oxygen and the increased NADH/NAD⁺ ratio inhibit the TCA cycle because NAD⁺ is needed to carry electrons. The buildup of NADH shifts metabolism toward lactate production to regenerate NAD⁺ and keep glycolysis running. This anaerobic condition impairs oxidative processes like the TCA cycle.

Answer 415

Answer: C) Conversion of pyruvate to lactate Explanation: In diabetic ketoacidosis, anaerobic conditions promote the conversion of pyruvate to lactate via lactate dehydrogenase. This allows for the regeneration of NAD⁺, enabling glycolysis to continue despite a lack of oxygen or mitochondrial function. This results in lactic acidosis.

Answer 416

Answer: B) Impaired ATP production Explanation: Pyruvate kinase deficiency results in decreased ATP production, which is essential for maintaining the shape and integrity of red blood cells. Without sufficient ATP, red blood cells become deformed and are destroyed in the spleen, leading to hemolysis and splenomegaly.

Answer 417

Answer: A) Increased fructose-2,6-bisphosphate levels Explanation: Insulin promotes glycolysis by increasing the levels of fructose-2,6-bisphosphate, which activates phosphofructokinase-1 (PFK-1) and inhibits fructose-1,6-bisphosphatase. This shift favors glycolysis over gluconeogenesis in the liver.

Answer 418

Answer: C) Phosphofructokinase-1 Explanation: During intense exercise, AMP levels increase, which activates phosphofructokinase-1 (PFK-1), the rate-limiting enzyme of glycolysis. This activation ensures that glycolysis proceeds quickly to meet the energy demands of the muscle.

Answer 419

Answer: A) Reduced insulin secretion from the pancreas Explanation: Glucokinase is found in the liver and pancreas and plays a key role in glucose sensing. A mutation in glucokinase reduces insulin secretion from the pancreas because it impairs the ability of pancreatic β-cells to sense elevated glucose levels and release insulin, leading to hyperglycemia.

Answer 420

Answer: C) Pyruvate levels Explanation: PFK-1 is the rate-limiting enzyme in glycolysis. A deficiency in PFK-1 would result in decreased glycolytic flux, leading to reduced production of pyruvate, the end product of glycolysis.

Answer 421

Answer: D) Conversion of pyruvate to lactate Explanation: In anaerobic conditions during intense exercise, pyruvate is converted to lactate via lactate dehydrogenase. This regenerates NAD⁺, allowing glycolysis to continue producing ATP even without oxygen.

Answer 422

Answer: D) Decreased gluconeogenesis Explanation: Fructose-2,6-bisphosphate promotes glycolysis by activating PFK-1 and inhibiting fructose-1,6-bisphosphatase, which reduces gluconeogenesis. In metabolic syndrome, high insulin levels elevate fructose-2,6-bisphosphate, favoring glycolysis and reducing gluconeogenesis.

Answer 423

A: In the inner mitochondrial membrane.

Answer 424

A: To generate ATP by transferring electrons from NADH and FADH₂ to oxygen.

Answer 425

A: NADH and FADH₂, both generated from the TCA cycle, glycolysis, and β-oxidation of fatty acids.

Answer 426

A: Complex I, also known as NADH dehydrogenase, transfers electrons from NADH to coenzyme Q (ubiquinone), and pumps protons into the intermembrane space.

Answer 427

A: Complex II, also called succinate dehydrogenase, is part of both the TCA cycle and the ETC, and it transfers electrons from FADH₂ to coenzyme Q without pumping protons.

Answer 428

A: Coenzyme Q transfers electrons from Complex I and Complex II to Complex III.

Answer 429

A: Complex III, also called cytochrome bc₁ complex, transfers electrons from coenzyme Q to cytochrome C and pumps protons into the intermembrane space

Answer 430

A: Cytochrome C shuttles electrons from Complex III to Complex IV.

Answer 431

A: Complex IV, also called cytochrome a₃ or cytochrome c oxidase, transfers electrons to oxygen, forming water and pumping protons into the intermembrane space.

Answer 432

A: Protons flow back into the mitochondrial matrix through ATP synthase (Complex V), driving the production of ATP from ADP and inorganic phosphate.

Answer 433

A: It transfers NADH from glycolysis (cytosol) into the mitochondria by converting oxaloacetate to malate, which crosses the mitochondrial membrane.

Answer 434

A: It transfers electrons from NADH in the cytosol to FADH₂ in the mitochondria, which is less efficient than the malate-aspartate shuttle.

Answer 435

A: Proton gradient dissipation occurs without ATP generation, leading to heat production (e.g., via uncoupling proteins or 2,4-dinitrophenol).

Answer 436

A: Rotenone inhibits Complex I, preventing electron transfer from NADH to coenzyme Q.

Answer 437

A: Cyanide binds to the Fe³⁺ in Complex IV (cytochrome c oxidase), preventing electron transfer to oxygen and halting ATP production.

Answer 438

A: Carbon monoxide binds to Fe²⁺ in Complex IV, preventing oxygen binding and disrupting electron transfer.

Answer 439

A: NADH yields approximately 2.5 ATP, and FADH₂ yields approximately 1.5 ATP.

Answer 440

A: Antimycin A inhibits Complex III, preventing electron transfer from coenzyme Q to cytochrome C.

Answer 441

A: Substrate-level phosphorylation directly generates ATP via an enzyme, while oxidative phosphorylation generates ATP through the proton gradient in the ETC.

Answer 442

A: The proton motive force is the electrochemical gradient of protons across the inner mitochondrial membrane, driving ATP synthesis through ATP synthase.

Answer 443

A. Inhibition of Complex I of the electron transport chain Explanation: The patient’s exposure to insecticides, his symptoms, and elevated lactate levels suggest rotenone poisoning, which is an inhibitor of Complex I of the ETC. Inhibition of Complex I prevents the transfer of electrons from NADH to coenzyme Q, disrupting ATP production and leading to increased anaerobic metabolism (lactic acidosis).

Answer 444

C. Succinate dehydrogenase Explanation: Succinate dehydrogenase is the only enzyme that participates in both the TCA cycle (by converting succinate to fumarate) and the electron transport chain (as Complex II). It transfers electrons from FADH₂ to coenzyme Q (ubiquinone) in the ETC.

Answer 445

C. Inhibition of Complex IV, preventing electron transfer to oxygen Explanation: Cyanide binds to the Fe³⁺ in cytochrome a₃ (part of Complex IV), preventing electron transfer to oxygen. This halts oxidative phosphorylation, leading to cellular hypoxia despite adequate oxygen in the blood, which explains the bright red venous blood and confusion. Sodium nitrite works by generating methemoglobin, which binds cyanide and protects cytochrome a₃.

Answer 446

B. Uncoupling of the proton gradient, causing increased heat production Explanation: 2,4-Dinitrophenol (DNP) is an uncoupling agent that causes protons to leak across the mitochondrial membrane without passing through ATP synthase. This disrupts ATP production and instead releases energy as heat, causing the patient’s feeling of warmth.

Answer 447

A. Inhibition of cytochrome c oxidase in Complex IV Explanation: Nitroprusside toxicity can cause cyanide poisoning, as it releases cyanide. Cyanide inhibits Complex IV (cytochrome c oxidase), leading to lactic acidosis, confusion, and bright red venous blood. This disrupts ATP production by preventing the transfer of electrons to oxygen.

Answer 448

B. Ubiquinone (coenzyme Q) Explanation: Statins reduce cholesterol synthesis by inhibiting HMG-CoA reductase, which also lowers the levels of coenzyme Q (ubiquinone), an essential component of the electron transport chain. Reduced coenzyme Q may contribute to statin-induced myopathy, and patients often take supplements to alleviate symptoms.

Answer 449

B. Thermogenin Explanation: Thermogenin (uncoupling protein 1, UCP-1) is found in brown adipose tissue. It uncouples oxidative phosphorylation by allowing protons to leak back into the mitochondrial matrix, generating heat instead of ATP. This is crucial in newborns and hibernating animals to maintain body temperature.

Answer 450

C. Uses the proton gradient to synthesize ATP Explanation: ATP synthase (Complex V) uses the proton gradient generated by the electron transport chain to synthesize ATP from ADP and inorganic phosphate. Protons flow down their concentration gradient through ATP synthase, which drives ATP production.

Answer 451

B. Dissipation of the proton gradient, generating heat instead of ATP Explanation: Aspirin overdose can uncouple oxidative phosphorylation, allowing protons to leak across the mitochondrial membrane. This dissipates the proton gradient, preventing ATP production and instead generating heat, leading to the patient’s fever.

Answer 452

A. Use of malate-aspartate vs glycerol phosphate shuttle Explanation: The difference in ATP yield (30 vs. 32 ATP per glucose molecule) depends on which shuttle system is used to transport NADH from glycolysis into the mitochondria. The malate-aspartate shuttle yields 32 ATP, while the glycerol phosphate shuttle yields 30 ATP due to the conversion of NADH to FADH₂, which generates fewer ATP.

Answer 453

Answer: Ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH) in the cytosol. Acetaldehyde is converted to acetate by aldehyde dehydrogenase (ALDH) in the mitochondria.

Answer 454

Answer: High NADH levels shunt oxaloacetate to malate, reducing its availability for gluconeogenesis, leading to hypoglycemia, especially in individuals with low glycogen stores.

Answer 455

Answer: High NADH inhibits the TCA cycle, causing acetyl-CoA to be diverted into ketone body production, leading to ketosis.

Answer 456

Answer: High NADH levels inhibit pyruvate dehydrogenase, leading to the shunting of pyruvate to lactate, resulting in lactic acidosis.

Answer 457

Answer: High NADH levels inhibit beta-oxidation and increase fatty acid synthesis, while glycerol-3-phosphate accumulates, leading to the formation of triglycerides and resulting in a fatty liver.

Answer 458

Answer: The MEOS (microsomal ethanol-oxidizing system) metabolizes excess ethanol via a cytochrome P450 pathway, generating free radicals and depleting NADPH, contributing to liver damage.

Answer 459

Answer: Disulfiram inhibits aldehyde dehydrogenase (ALDH), causing a buildup of acetaldehyde, leading to unpleasant symptoms (e.g., flushing, nausea) when alcohol is consumed.

Answer 460

Answer: Fomepizole is used to inhibit alcohol dehydrogenase (ADH), preventing the formation of toxic metabolites such as formic acid (from methanol) and oxalate (from ethylene glycol).

Answer 461

Answer: Alcohol flushing syndrome is caused by a deficiency in aldehyde dehydrogenase (ALDH2), leading to the accumulation of acetaldehyde. It is more common in Asian populations.

Answer 462

C) Inhibition of beta-oxidation Explanation: Ethanol metabolism generates large amounts of NADH. High levels of NADH inhibit processes that require NAD+, including beta-oxidation of fatty acids. This leads to the accumulation of fatty acids and contributes to the development of fatty liver in chronic alcohol users.

Answer 463

B) Inhibition of aldehyde dehydrogenase Explanation: Disulfiram (Antabuse) inhibits aldehyde dehydrogenase, leading to the accumulation of acetaldehyde when alcohol is consumed. The buildup of acetaldehyde causes unpleasant symptoms such as flushing, nausea, and palpitations, which act as a deterrent to alcohol consumption.

Answer 464

C) Inhibition of gluconeogenesis due to oxaloacetate shunting to malate Explanation: High levels of NADH produced during alcohol metabolism shunt oxaloacetate to malate, reducing the availability of oxaloacetate for gluconeogenesis. As a result, gluconeogenesis is impaired, leading to hypoglycemia, especially when glycogen stores are depleted.

Answer 465

B) Increased conversion of acetate to acetyl-CoA Explanation: Ethanol metabolism produces acetate, which is converted into acetyl-CoA. When the TCA cycle is inhibited by high NADH levels, acetyl-CoA is shunted toward ketone body production, leading to ketoacidosis in chronic alcoholics.

Answer 466

C) Inhibition of pyruvate dehydrogenase by NADH Explanation: High NADH levels inhibit pyruvate dehydrogenase, preventing pyruvate from entering the TCA cycle. Instead, pyruvate is converted to lactate, leading to lactic acidosis, a common complication in chronic alcohol abuse.

Answer 467

E) Increased glycerol-3-phosphate leading to triglyceride formation Explanation: In alcoholics, high levels of NADH inhibit beta-oxidation and promote fatty acid synthesis. Glycerol-3-phosphate accumulates because its metabolism is impaired, and it combines with fatty acids to form triglycerides, contributing to fatty liver.

Answer 468

C) Aldehyde dehydrogenase Explanation: Alcohol flushing syndrome is caused by a deficiency in aldehyde dehydrogenase (ALDH2), leading to the accumulation of acetaldehyde after alcohol consumption. This condition is more common in individuals of East Asian descent.

Answer 469

B) Inhibits alcohol dehydrogenase Explanation: Fomepizole inhibits alcohol dehydrogenase, preventing the metabolism of methanol into toxic metabolites like formaldehyde and formic acid. This treatment reduces the formation of toxic byproducts that lead to methanol poisoning.

Answer 470

C) Microsomal ethanol-oxidizing system (MEOS) Explanation: The MEOS pathway, part of the cytochrome P450 system, becomes more active with excessive alcohol consumption. It generates free radicals and consumes NADPH, contributing to oxidative stress and liver damage, which can lead to hepatitis and cirrhosis in alcoholics.

Answer 471

C) High lactic acid competes with uric acid for excretion in the kidney Explanation: High levels of lactic acid in alcoholics compete with uric acid for excretion in the proximal tubule via the URAT1 transporter. This results in decreased uric acid excretion and hyperuricemia, which can trigger gout attacks, especially after excessive alcohol consumption.

Answer 472

a) Ferrochelatase and ALA dehydratase b) Protoporphirin and ALA (blood) c) Mycrocytic anemia peripheral smear: basophilic stippling bone marrow: ringed sideroblasts GI and kidney disease Children: Mental deterioration Adult: headache, memory loss, demyelination (peripheral neuropathy)

BIOCHEMSTRY Flashcards

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