Biochem Final

Amino Acid, Steroid, & Cholesterol Metabolism

1. Neurotransmitters derived from tyrosine:

   • Dopamine: Produced via tyrosine hydroxylase (rate-limiting step) and DOPA decarboxylase.

   • Norepinephrine: Synthesized from dopamine by dopamine beta-hydroxylase.

   • Epinephrine: Synthesized from norepinephrine by phenylethanolamine N-methyltransferase (PNMT).

2. Physiological effects of aldosterone:

   • Sodium reabsorption: Increases sodium channels (ENaC) in distal tubules/collecting ducts.

   • Potassium excretion: Stimulates K+ secretion via renal tubules.

   • Regulates fluid balance: Increases extracellular fluid volume and blood pressure.

3. Actions/reactions catalyzed by glutamate decarboxylase (GAD):

   • Converts glutamate (excitatory neurotransmitter) to GABA (inhibitory neurotransmitter).

   • Requires pyridoxal phosphate (PLP) as a cofactor.

4. Allosteric regulation mechanisms with examples:

   • Positive regulation: Oxygen binding to hemoglobin increases affinity at other sites.

   • Negative regulation: ATP inhibiting phosphofructokinase (PFK) in glycolysis.

   • Feedback inhibition: Isoleucine inhibiting threonine deaminase in amino acid biosynthesis.

5. Tryptophan is the amino acid precursor for serotonin synthesis via the enzyme tryptophan hydroxylase.

6. Enzymes catalyzing transdeamination:

   • Aminotransferase: Transfers amino groups between amino acids and alpha-keto acids.

   • Glutamate dehydrogenase: Oxidatively deaminates glutamate to alpha-ketoglutarate.

7. Actions of S-Adenosyl Methionine (SAM):

   • Methyl donor: DNA, RNA, and protein methylation.

   • Precursor for polyamines: Spermidine and spermine synthesis.

   • Structure: Contains an adenosine group, sulfur, and a methionine moiety.

8. Steroid production sites:

   • Cortisol: Adrenal cortex (zona fasciculata).

   • Aldosterone: Adrenal cortex (zona glomerulosa).

   • Testosterone: Testes (Leydig cells).

   • Estradiol: Ovaries (granulosa cells).

9. Enzyme concentration changes indicating liver damage:

   • Elevated ALT (alanine aminotransferase).

   • Elevated AST (aspartate aminotransferase).

10. Precursors of creatine and phosphocreatine:

    • Glycine: Provides carbon and nitrogen.

    • Arginine: Donates guanidino group.

    • Methionine: Provides a methyl group via SAM.

11. Enzymes regulating the urea cycle:

    • Carbamoyl phosphate synthetase I: Rate-limiting step.

    • Ornithine transcarbamylase (OTC).

    • Argininosuccinate synthetase.

    • Argininosuccinate lyase.

    • Arginase: Cleaves arginine into urea and ornithine.

12. Symptoms of Cushing’s syndrome:

    • Hyperglycemia: Increased gluconeogenesis.

    • Central obesity: Fat redistribution.

    • Hypertension: Sodium retention.

    • Osteoporosis: Decreased bone mineral density.

13. Amino acids providing carbon skeleton for acetyl CoA/acetoacetyl CoA:

    • Ketogenic amino acids: Leucine, lysine.

    • Partially ketogenic: Isoleucine, phenylalanine, tryptophan, tyrosine.

14. Side effects of chronic steroid use:

    • Suppressed immune function.

    • Osteoporosis.

    • Muscle wasting.

    • Adrenal insufficiency on withdrawal.

15. Metabolic cycles:

    • Alanine cycle: Transports nitrogen from muscles to the liver.

    • Urea cycle: Removes toxic ammonia.

    • Cori cycle: Converts lactate back to glucose.

    • Citric acid cycle: Generates ATP and electron carriers.

16. Cholesterol precursors:

    • Steroid hormones: Cortisol, aldosterone, sex hormones.

    • Bile acids: Chenodeoxycholic acid, cholic acid.

    • Vitamin D: Cholecalciferol.

17. Inactivation of HMG-CoA reductase:

    • Glucagon inhibits through phosphorylation (via AMP-activated protein kinase).

18. Cholesterol biosynthesis precursors:

    • Acetyl-CoA → HMG-CoA → Mevalonate.

19. Statin supplements:

    • Coenzyme Q10 (CoQ10): Counteracts myopathy.

20. Rate-limiting enzyme for cholesterol biosynthesis:

    • HMG-CoA reductase.

21. PCSK9 inhibitors:

    • Drugs: Alirocumab, Evolocumab.

    • Mechanism: Blocks PCSK9 binding to LDL receptors, promoting receptor recycling.

22. Difference between bile acids and bile salts:

    • Bile acids: Non-conjugated.

    • Bile salts: Conjugated with taurine or glycine.

    Vitamins/Micronutrients

    1. Micronutrients include:

       • Vitamins: Organic compounds essential for metabolism.

       • Minerals: Inorganic elements like iron, zinc, and magnesium.

    2. Water-soluble vitamins:

       • Nine water-soluble vitamins: B1, B2, B3, B5, B6, B7, B9, B12, and Vitamin C.

       • Energy-releasing B-complex vitamins: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), and B7 (biotin).

       • Hematopoietic B-complex vitamins: B9 (folic acid) and B12 (cobalamin).

       • Other B-complex vitamins: B6 (pyridoxine, pyridoxal, pyridoxamine).

    3. Fat-soluble vitamins:

       • Four fat-soluble vitamins: A, D, E, and K.

    4. Vitamin A forms and sources:

       • Forms: Retinol, retinal, retinoic acid (active forms).

       • Sources:

         • Retinol: Animal products like liver and dairy.

         • Beta-carotene: Carrots, sweet potatoes, and green leafy vegetables.

       • Most important provitamin A carotenoid: Beta-carotene.

    5. Vitamin A metabolites (active/inactive forms):

       • Active: Retinal, retinoic acid.

       • Inactive: Retinyl esters.

    6. Retinoids definition and examples:

       • Definition: Vitamin A and its derivatives.

       • Examples: Retinol, retinal, retinoic acid.

    7. Vitamin A metabolism:

       • Retinol is the precursor for vitamin A and is converted into retinyl esters for storage.

    8. Retinoic acid receptors (RAR):

       • Nuclear receptors regulating gene expression.

    9. Vitamin A in medical treatments:

       • Isotretinoin: Treats severe acne.

       • All-trans retinoic acid (ATRA): Treats acute promyelocytic leukemia and psoriasis.

    10. Hypervitaminosis A:

        • Excess vitamin A causing toxicity.

        • Symptoms: Nausea, headache, liver damage, blurred vision.

        • High-risk group: Pregnant women (teratogenic effects).

    11. Vitamin D:

        • Precursor: 7-dehydrocholesterol (converted in the skin via UV light).

        • Metabolism: Hydroxylated in the liver (25-OH-D3) and kidneys (1,25-OH-D3, active form).

        • Regulation:

          • Stimulated by: Parathyroid hormone (PTH).

          • Inhibited by: High calcium, phosphate, and 1,25-OH-D3 levels.

    12. Functions of Vitamin D:

        • Enhances calcium and phosphate absorption in intestines.

        • Promotes bone mineralization.

        • Modulates immune system function.

    13. Diseases caused by Vitamin D deficiency:

        • Rickets (children).

        • Osteomalacia (adults).

        • Hypocalcemia.

    14. Functions of Vitamin E:

        • Antioxidant (protects cell membranes from oxidative damage).

        • Prevents lipid peroxidation.

        • Supports immune function.

    15. Vitamin K:

        • Function: Gamma-carboxylation of clotting factors II, VII, IX, X.

        • Enzyme cofactor: Vitamin K-dependent carboxylase.

        • Warfarin inhibition: Blocks vitamin K epoxide reductase.

        • Sources: Leafy greens (phylloquinone), gut microbiota (menaquinone).

        • Toxicity in infants: Can cause hemolysis and jaundice.

    16. Vitamin C:

        • Chemical name: Ascorbic acid.

        • Functions:

          • Antioxidant.

          • Coenzyme for collagen synthesis and norepinephrine production.

          • Enhances iron absorption.

        • Deficiency symptoms: Scurvy (fatigue, bleeding gums, poor wound healing).

        • Antioxidant synergy: Works with Vitamin E.

    17. Vitamin B family members:

        • B1 (Thiamine), B2 (Riboflavin), B3 (Niacin), B5 (Pantothenic Acid), B6 (Pyridoxine), B7 (Biotin), B9 (Folic Acid), B12 (Cobalamin).

    18. Vitamin B1 (Thiamine):

        • Bioactive form: Thiamine pyrophosphate (TPP).

        • Deficiency syndromes:

          • Beriberi: Dry (neurological symptoms) or wet (cardiac symptoms).

          • Wernicke-Korsakoff syndrome: Alcoholism-related, with confusion, ataxia, and memory loss.

    19. Vitamin B2 (Riboflavin):

        • Active forms: FMN (flavin mononucleotide), FAD (flavin adenine dinucleotide).

        • Functions: Electron carriers in redox reactions (e.g., TCA cycle).

    20. Vitamin B3 (Niacin):

        • Active forms: NAD, NADP.

        • Deficiency: Pellagra (dermatitis, diarrhea, dementia).

        • Therapeutic use: Lowers LDL and increases HDL cholesterol.

    21. Vitamin B5 (Pantothenic Acid):

        • Component of coenzyme A (CoA), essential for fatty acid metabolism.

    22. Vitamin B6:

        • Includes pyridoxine, pyridoxal, and pyridoxamine.

        • Functions: Amino acid metabolism, neurotransmitter synthesis.

        • Deficiency: Can cause peripheral neuropathy, worsened by isoniazid.

    23. Vitamin B7 (Biotin):

        • Prosthetic group for carboxylation reactions (e.g., pyruvate carboxylase).

    24. Vitamin B9 (Folic Acid):

        • Active form: Tetrahydrofolate (THF).

        • Functions: DNA synthesis, amino acid metabolism.

        • Deficiency: Macrocytic anemia, neural tube defects (spina bifida, anencephaly).

    25. Vitamin B12 (Cobalamin):

        • Essential for methylation reactions and DNA synthesis.

        • Deficiency: Pernicious anemia (macrocytic, megaloblastic anemia).

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    Clinical Applications

    1. Symptoms of Type 1 Diabetes:

       • Polyuria, polydipsia, polyphagia.

       • Weight loss despite increased appetite.

       • Hyperglycemia and ketoacidosis.

    2. Actions of insulin:

       • Stimulates glucose uptake via GLUT4.

       • Promotes glycogenesis, lipogenesis, and protein synthesis.

       • Inhibits gluconeogenesis and lipolysis.

    3. Effects of insulin resistance:

       • Decreased glucose uptake.

       • Hyperglycemia.

       • Increased risk of metabolic syndrome and type 2 diabetes.

    4. Actions of glucagon:

       • Stimulates glycogenolysis and gluconeogenesis.

       • Mobilizes fatty acids via lipolysis.

    5. Comparison of insulin vs. glucagon:

       • Insulin: Anabolic hormone; promotes nutrient storage.

       • Glucagon: Catabolic hormone; mobilizes stored energy.

    6. Primary fuel consumed during fed state:

       • Brain: Glucose.

       • Muscle: Glucose (or fatty acids in fasting state).

    7. Enzymes activated by glucagon in fasting state:

       • Glycogen phosphorylase.

       • Fructose-1,6-bisphosphatase.

       • Hormone-sensitive lipase.

    8. Mechanisms of diabetes medications:

       • Metformin: Reduces hepatic gluconeogenesis, increases insulin sensitivity.

       • Sulfonylureas: Stimulate insulin release by closing K+ channels in beta cells.

       • Thiazolidinediones: Enhance peripheral insulin sensitivity via PPAR-γ activation.

    9. Ketoacidosis:

       • High in type 1 diabetes (due to insulin deficiency).

       • Low in type 2 diabetes (residual insulin prevents ketosis).