Medical Biochemistry

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Medical Biochemistry

• Overview

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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

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Metabolism

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

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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

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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

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Chemistry Review

• Inorganic Chemistry
• Organic Chemistry
• Biochemistry

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Cations and AnionsMono-,Di, and Trivalent
Na Fe,Fe Cu, Cu HCO3- NO2-
K NH4 PO4--- HClO-
H Cl-, F- SO4--
Mg,Mn I- OH-
Ca CO3-- NO3-
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Inorganic Chemistry

• Water
• Poiseulles Law
• Non-compressible
• Friction
• Diameter associated with area
• Pressure
• Viscosity (n)
• Length (l)

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Poiseulles Law Continued

• Linear decrease in size decreases area
  exponentially
• Arterial Plaque Formation
• Example of Arteriosclerosis
• If r10 r410000
• If r9 (10less) r46561 (35 less)
• If r5 (50less) r4625 (93.75 less!)

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Concentration of Water

• 1 liter1000 gm
• 18gm/mole (Gram Equivalent)
• O 16
• 2 H 2
• Number of Moles per liter
• Number of Molecules per liter

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Example of Number of Molecules of Oxygen in a
Breath

• Example to be completed by student
• Assume 1 liter breath
• Diatomic Oxygen

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pH

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

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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

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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

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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

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Chemical Bonds

• Ionic
• Crystal
• Covalent
• Hydrogen (Weak)
• Van der Waals Forces

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Reactions

• Exothermic
• Endothermic

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Elementary Composition of Body-Dry Weight Basis
Carbon50 P2.5 Magnesium0.1
Oxygen20 K1.0 Iron0.01
Hydrogen10 Sulfur0.8 Mn0.001
Nitrogen8.5 Sodium0.4 Iodine0.00005
Calcium4.0 Chlorine0.4 Many Others
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Organic Chemistry

• CHO Primarily
• Ethane, Ethylene,Acetylene
• Benzene
• Methane

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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
  (Ltrectus-right sinister-left)

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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

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Functional Aspect of Groups

• Alkyl CH3-(CH2)n-
• Alkene -CC-
• Aromatic
• Alcohol R-OH
• Amines R-NH2
• Sulfur Derivatives
• R-SH Sulfhydryl (Thiol)
• R-S-S-H Disulfide

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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

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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

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Consistancy of Blood Plasma (Age 40)
Na136-149 meq/L Albumin3.5-5.0 g/dl Cholesterol (total)150-260mg/dl Phenylalanine0.8-1.8mg/dl
Chloride118-132 meq/L Transferrin220-400 mg/dl Triglyceride56-298mg/dl Iron50-170ug/dl
Bicarbonate 18-23 meq/L Ceruloplasmin18-45mg/dl Calcium8.4-10.2mg/dl Vitamin A 30-65ug/dl
Protein6.4-8.3 g/dl Glucose(fasting)70-105mg/dl Glutamine6-16mg/dl Vitamin D 14-42 ng/dl (25-OH)
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Animal Cell Structure

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

Nucleus
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Plant Cell Structure

• Chloroplasts
• Cell Wall
• Starch Granules
• Etc.

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Plant and Animal Biochemistry

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

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Starches

• Amylose
• Amylopectin
• Glycogen

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Sugars

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

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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)

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Cellulose

• Relatively Linear
• Beta 1,4

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Other Sugars

• Chitin
• Arabinogalactan
• Olimeric Proanthocyanidins (OPCs)

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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

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Enzymes

• Isomaltase
• Lactase (?-galactosidase)
• Sucrase
• Maltase

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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

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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

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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

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If you ate a 3oz. Donut in the morning assume
100 carbohydrate---

• What of the donuts energy would be used by the
  brain?
• Brain needs 100-120gm of glucose per day.
  (400-480 Kcal/day)
• 340Kcal/440Kcal x 100 75

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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

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Gluconeogenesis

• Occurs primarily in liver
• Stimulated by epinephrine

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Glucose Homeostasis

• Hypoglycemic Action-Insulin
• Hyperglycemic Action-Glucagon, epinephrine,cortiso
  l, 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

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Alcoholism and Hypoglycemia

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

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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.