Medical Biochemistry Robert F. Waters, PhD

1. Medical BiochemistryRobert F. Waters, PhD Overview

2. Medical Biochemistry Overview • Course Overview • Carbohydrate Metabolism • Sugars, Starches, Digestion, Absorption, Energy • Lipid Metabolism • Digestion, Absorption, Transport, Mobilization • Amino Acids and Proteins • Production, Breakdown, Conversion • Nucleic Acids, DNA and RNA • Production, Breakdown • Medical Genetics

3. Metabolism • Anabolism • Catabolism • Conversion into derivatives • e.g histidine to histamine • Tyrosine to thyroxines • Tyrosine to melanin • Choline to acetylcholine

4. Mycotoxins (Silent Killer) • Example is aflatoxin (B1,B2,G1,G2) • Converted to M1 in liver and P1 in kidney (urine) • Carcinogenic • Negatively affects immune system • Where do they come from? • Molds growing on plant material produce toxins • Other toxins • Fumonison(horses) [10-15-ppm], vomitoxin, bovarison

5. Low Level Radiation • Proposed by Dr. Sternglas • Sr90 is a - emmitter • Mimics calcium in bone marrow • Negative impact on immune system • Low birth weights • High cancer rates • MS (Multiple Sclerosis) • Neurological Disorders

6. Chemistry Review • Inorganic Chemistry • Organic Chemistry • Biochemistry

7. Cations and Anions—Mono-,Di, and Trivalent

8. Inorganic Chemistry • Water • Poiseulles’ Law • Non-compressible • Friction • Diameter associated with area • Pressure • Viscosity (n) • Length (l)

9. Poiseulles’ Law Continued • Linear decrease in size decreases area exponentially • Arterial Plaque Formation • Example of Arteriosclerosis • If r=10 r4=10000 • If r=9 (10%less) r4=6561 (35% less) • If r=5 (50%less) r4=625 (93.75% less!)

10. Concentration of Water • 1 liter=1000 gm • 18gm/mole (Gram Equivalent) • O = 16 • 2 H = 2 • Number of Moles per liter • Number of Molecules per liter

11. Example of Number of Molecules of Oxygen in a Breath • Example to be completed by student • Assume 1 liter breath • Diatomic Oxygen

12. pH • Hydrogen Ion Concentration • Dissociation of Water • P= - logarithm • 7 + 7 = 14 • Acidity vs. Alkalinity • pH in living systems

13. Atomic Structure • Bohr Concept • Shells, sub-shells, orbitals • Quantum structure vs. Sun and Planet revolution • Electron spin on orbitals • Example of Chlorophyll • Pauli Exclusion Principle

14. Pauli Exclusion Principle • Example of Carbon • Carbon • 2 electrons in first shell (sub-shell) (1s) • Second shell has two sub-shells 2s and 2p • 2s has one orbital and 2p has 3 orbitals • Initially 2s has two electrons and two of the three 2p orbitals have 1 electron • 1 2s electron is promoted to 3rd 2p orbital

15. Pauli Exclusion Principle Cont. • Now forms sp3 Configuration • 2 electrons in 1s and 1 electron in 2s orbital and each of the three 2p orbitals • Carbon now has 4 electrons to share giving it a valence of 4 • Example of Methane with angle between hydrogen bonds being 109.5o

16. Chemical Bonds • Ionic • Crystal • Covalent • Hydrogen (Weak) • Van der Waals Forces

17. Reactions • Exothermic • Endothermic

18. Elementary Composition of Body-Dry Weight Basis

19. Organic Chemistry • CHO Primarily • Ethane, Ethylene,Acetylene • Benzene • Methane

20. Isomers • Structural Isomers • Ethanol and Dimethyl Ether • Geometric Isomers • Trans-2-butene, Cis-2-butene • Stereochemistry and Stereoisomerism • Polarimeter • D vs. L • d-Lactate, l-Lactate (dextrorotary(+), levorotary(-)) • Chirality (rotational aspect of molecule) • Enantiomeres (Isomers that are mirror images of each other) • Same physical properties except for rotation of light---maybe different biochemical properties! • Racemic mixture-mixture in solution of enantiomeres • Orientation around a chiral center based on atomic number where highest atomic number has highest priority. Highest to lowest from left to right is R and the opposite direction is S (Lt:rectus-right & sinister-left)

21. Major Groups • R-OH Hydroxyl • R-NHx Amino • R-COOH Carboxyl • R-CHO Carbonyl (Aldehyde) • R-CO-R Ketone • R-CH3 Methyl • R-PO4 Phosphate • R-SH Sulfhydryl

22. Functional Aspect of Groups • Alkyl CH3-(CH2)n- • Alkene -C=C- • Aromatic • Alcohol R-OH • Amines R-NH2 • Sulfur Derivatives • R-SH Sulfhydryl (Thiol) • R-S-S-H Disulfide

23. Functional Aspect of Groups-Cont. • Carbonyl Groups (R-CHO) • Aldehyde R-CHO • Ketone R-CO-R • Carboxylic Acid R-COOH • Ester R-COO-R’ • Amide R-CO-NH2

24. Multifunctional Groups • Hydroxy Acid R-COH-COOH • Keto Acid R-CO-COOH • Dicarboxylate HOOC-R-COOH • Phosphates • PO4= Pi • Pyroposphate PPi • Triphosphate R-P-P-P

25. Consistancy of Blood Plasma (Age 40)

26. Animal Cell Structure • Plasma Membrane • Nucleus • Nucleolus • Nuclear Membrane • RER • SER • MTOC (Centrioles) • Mitochondria • Cytosol • Cytoplasm? • Golgi Body • Vesicles • Lysosomes • Microsomes Nucleus

27. Plant Cell Structure • Chloroplasts • Cell Wall • Starch Granules • Etc.

28. Plant and Animal Biochemistry • Plant Biochemistry • Animal Biochemistry • Animal Science vs. Human Nutrition

29. Starches • Amylose • Amylopectin • Glycogen

30. Sugars • Sugars • Monosaccharides • Glucose, fructose, galactose, mannose • Disaccharides • Lactose, sucrose, maltose • Polysaccharides • Glycogen, starch, cellulose • Triose • Pentose • Hexose

31. Glycogen • Branched Chain Polysaccharide • Approx. every 8 glucose a branch (alpha 1,6) • Bond between glucose (alpha 1,4) • Efficient energy storage • Mainly liver (also other tissues)

32. Cellulose • Relatively Linear • Beta 1,4

33. Other Sugars • Chitin • Arabinogalactan • Olimeric Proanthocyanidins (OPCs)

34. Digestion • Breakdown of Starch • -1,4 •  -Amylase • Maltotriose OOO • Maltose OO • Dextrins – fragments of branched and unbranched starches • Isomaltose Two Glucose -1,6 • Sucrose • Lactose (Infantile) • Trehalase-Some people lack enzyme and acts like mushroom poisoning. • Trehalose in foods like mushrooms

35. Enzymes • Isomaltase • Lactase (-galactosidase) • Sucrase • Maltase

36. Insulin/Glucagon and Glucose-Glucose Homeostasis • Main Metabolic Fuels are Glucose and Fatty Acids • Long Chain Fatty Acids are Ideal Fuel Storage 9 kcal/g vs. 4 kcal/g for carbs and proteins • Amino Acids can be fuel during fasting, illness, or injury

37. If you ate a 3oz. Donut in the morning & assume 100% carbohydrate--- • How many calories would you have ingested? • ~4 Kcal/g • 16 oz/lb • 454 gm/lb • 3oz/16oz x 454gm = 85 gm • 85gm x 4 Kcal/gm = 340 Kcal/donut

38. If you ate a 3oz. Donut in the morning & assume 100% carbohydrate--- • What % of your average daily caloric intake does this represent? • 1800 Kcal / day (1500-2200) • 340Kcal/1800Kcal X 100 = ~20%

39. If you ate a 3oz. Donut in the morning & assume 100% carbohydrate--- • What % of the donut’s energy would be used by the brain? • Brain needs 100-120gm of glucose per day. (400-480 Kcal/day) • 340Kcal/440Kcal x 100 = ~75%

40. If you ate a 3oz. Donut in the morning & assume 100% carbohydrate--- • How long could the brain function on the energy from one donut? • Brain needs 100-120 gm or ~440Kcal/day • 340Kcal/440Kcal x 24 hrs = 18 hrs

41. Gluconeogenesis • Occurs primarily in liver • Stimulated by epinephrine

42. Glucose Homeostasis • Hypoglycemic Action-Insulin • Hyperglycemic Action-Glucagon, epinephrine,cortisol, Growth Hormone (GH) • Insulin • Produced by -cells (70% of islet cells) • Glucagon secreted by -cells • Pre-proinsulin, pro-insulin, insulin • C-peptide (-cell Assessment) • Insulin-2 chains (-21AAand -30AA) connected by 2 disulfide bonds • Biphasic Secretion • Insulin Receptors and Glucose Receptors • TNF-  inhibits glucose receptor • Type I and Type II Diabetes

43. Alcoholism and Hypoglycemia • Inhibits Thiamine absorption in gut • Inhibits Lactate Dehydrogenase (Reverse) • Liver Pyruvate levels drop • Hypoglycemic due to inhibited gluconeogenesis (anabolic)

44. Alcohol Consumption Continued; Animal cells contain alcohol dehydrogenase (ADH) which oxidizes ethanol to acetaldehyde. Acetaldehyde is oxidized to acetate by acetaldehyde dehydrogenase (AcDH). Acetaldehyde and acetate are toxic leading to the many side effects (the hangover) that are associated with alcohol consumption. The ADH and AcDH catalyzed reactions also leads to the reduction of NAD+ to NADH. The metabolic effects of ethanol intoxication stem from the actions of ADH and AcDH and the resultant cellular imbalance in the NADH/NAD+. The reduction in NAD+ impairs the flux of glucose through glycolysis at the glyceraldehyde-3-phosphate dehydrogenase reaction, thereby limiting energy production. Additionally, there is an increased rate of hepatic lactate production due to the effect of increased NADH on direction of the hepatic lactate dehydrogenase (LDH) reaction. This reverseral of the LDH reaction in hepatocytes diverts pyruvate from gluconeogenesis leading to a reduction in the capacity of the liver to deliver glucose to the blood.