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Medical Biochemistry

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Medical Biochemistry Overview Medical Biochemistry Overview Course Overview Carbohydrate Metabolism Sugars, Starches, Digestion, Absorption, Energy Lipid Metabolism ... – PowerPoint PPT presentation

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Title: Medical Biochemistry


1
Medical Biochemistry
  • 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 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-
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 r10 r410000
  • If r9 (10less) r46561 (35 less)
  • If r5 (50less) r4625 (93.75 less!)

10
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

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
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
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
    (Ltrectus-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 -CC-
  • 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)
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)
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 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

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,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

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.

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