High-Yield Biochemistry for USMLE Step 1

Introduction

• Presenter: Ethan Plotzker
• Focus: High-yield biochemistry topics for USMLE Step 1

Vitamins

Thiamine (Vitamin B1)

• Clinical Context: Beriberi
  • Types: Wet and Dry
  • Wet Beriberi: High-output heart failure, muscle wasting, nerve damage
• Wernicke Encephalopathy:
  • Mnemonic: CAN O' Beer
  • Symptoms: Confusion, Ataxia, Nystagmus, Ophthalmoplegia
  • Risk Factor: Alcoholism
• Korsakoff Syndrome: Confabulation, damage to mammillary bodies
• Brain Structures Affected: Medial dorsal nucleus of the thalamus, mammillary bodies

Niacin (Vitamin B3)

• Deficiency: Pellagra
  • Symptoms: Dermatitis, Diarrhea, Dementia, (Death)
  • Image: Necklace distribution of dermatitis
• Hartnup Disease: Defective transporters in kidneys, leads to tryptophan loss
• Role: NAD+ and NADP+ in energy production (glycolysis, TCA cycle)

Folate (Vitamin B9)

• Sources: Leafy greens
• Importance in Pregnancy: Prevents neural tube defects
• Deficiency: Macrocytic anemia, elevated homocysteine
• Absorption Site: Jejunum

Cobalamin (Vitamin B12)

• Deficiency Symptoms: Megaloblastic anemia, neuropathy, elevated homocysteine and methylmalonic acid
• Sources: Animal products
• Condition: Pernicious anemia (antibodies against intrinsic factor)

Vitamin C (Ascorbic Acid)

• Role: Collagen synthesis, hydroxylation of proline and lysine
• Deficiency: Scurvy (corkscrew hairs, joint bleeding)
• At-risk Diet: Tea and toast diet

Vitamin A (Retinol)

• Role: Vision (photoreceptor proteins), acne treatment
• Deficiency: Night blindness, Bitot's spots
• Therapeutic Use: ATRA for APML

Vitamin D

• Forms: D2 (Ergocalciferol), D3 (Cholecalciferol)
• Role: Calcium homeostasis
• Deficiency: Rickets (children), Osteomalacia (adults)
• Activation: Requires hydroxylation in kidneys

Vitamin E (Tocopherol)

• Role: Antioxidant
• Deficiency: Hemolytic anemia, neurological symptoms

Vitamin K

• Role: Clotting functions, interacts with warfarin
• Deficiency in Newborns: Due to lack of intestinal flora

Metabolic Disorders

Fructose Metabolism Disorders

• Essential Fructosuria: Benign, fructokinase deficiency, fructose in urine
• Hereditary Fructose Intolerance: Aldolase B deficiency, hypoglycemia, dietary management

Galactose Metabolism Disorders

• Galactokinase Deficiency: Cataracts, developmental delay
• Classic Galactosemia: Galactose-1-phosphate uridyltransferase deficiency

Glycogen Storage Diseases

• Von Gierke Disease (Type I): Glucose-6-phosphatase deficiency, fasting hypoglycemia
• Pompe Disease (Type II): Alpha-1,4-glucosidase deficiency, cardiomyopathy
• Cori Disease (Type III): Debranching enzyme deficiency, mild hypoglycemia
• McArdle Disease (Type V): Muscle glycogen phosphorylase deficiency

Lysosomal Storage Diseases

• Metachromatic Leukodystrophy: Arylsulfatase A deficiency, demyelination
• Tay-Sachs Disease: Hexosaminidase A deficiency, cherry-red macula
• Niemann-Pick Disease: Sphingomyelinase deficiency, hepatosplenomegaly
• Fabry Disease: Alpha-galactosidase A deficiency, neuropathy
• Gaucher Disease: Glucocerebrosidase deficiency, hepatosplenomegaly
• Krabbe Disease: Galactocerebrosidase deficiency, optic atrophy
• Hunter & Hurler Syndromes: Mucopolysaccharidoses, differing severities

Other Metabolic Conditions

• Cystinuria: Amino acid reabsorption defect, kidney stones
• Homocystinuria: Enzyme deficiencies affecting methionine metabolism
• Phenylketonuria (PKU): Phenylalanine hydroxylase deficiency
• Maple Syrup Urine Disease: Branched-chain amino acid metabolism disorder

Genetic Abnormalities

• Trisomy 13 (Patau Syndrome): Holoprosencephaly, cleft lip
• Trisomy 18 (Edwards Syndrome): Rocker-bottom feet, clenched fists
• Trisomy 21 (Down Syndrome): Cardiac defects, facial dysmorphisms

Conclusion

• Q&A Session: Opportunity for questions and discussion.
• Contact Information: Available for further queries.