Locomotion module Biochemistry Omer M. Abdalla, PhD molecular medicine.
Medical Biochemistry Robert F. Waters, PhD
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Transcript of Medical Biochemistry Robert F. Waters, PhD
Medical BiochemistryMedical BiochemistryRobert F. Waters, PhDRobert F. Waters, PhD
Overview
Medical Biochemistry Medical Biochemistry OverviewOverview
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
MetabolismMetabolism
AnabolismCatabolismConversion into derivatives
– e.g histidine to histamine– Tyrosine to thyroxines– Tyrosine to melanin– Choline to acetylcholine
Mycotoxins (Silent Killer)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
Low Level RadiationLow 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
Chemistry ReviewChemistry Review
Inorganic ChemistryOrganic ChemistryBiochemistry
Cations and Anions—Cations and Anions—Mono-,Di, and TrivalentMono-,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
-
Inorganic ChemistryInorganic Chemistry
Water– Poiseulles’ Law
Non-compressible Friction Diameter associated with area Pressure Viscosity (n) Length (l)
nl
pr
nl
rprQ
88
))()(( 422
PinPoutp
2r
Poiseulles’ Law ContinuedPoiseulles’ 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!)
Concentration of WaterConcentration of Water
1 liter=1000 gm18gm/mole (Gram Equivalent)
– O = 16– 2 H = 2
Number of Moles per liter
Number of Molecules per liter
lmmolegm
/5.55/18
1000
]10*02.6[*5.55 23
Example of Number of Example of Number of Molecules of Oxygen in a Molecules of Oxygen in a BreathBreathExample to be completed by student
– Assume 1 liter breath– Diatomic Oxygen
pHpH Hydrogen Ion Concentration Dissociation of Water
P= - logarithm
7 + 7 = 14 Acidity vs. Alkalinity pH in living systems
14101]][[ OHHkw
pkwpOHpH
Atomic StructureAtomic Structure
Bohr Concept– Shells, sub-shells, orbitals– Quantum structure vs. Sun and Planet
revolution– Electron spin on orbitals– Example of Chlorophyll– Pauli Exclusion Principle
Pauli Exclusion PrinciplePauli Exclusion Principle
Example of CarbonCarbon
– 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
Pauli Exclusion Principle Pauli Exclusion Principle Cont.Cont.
Now forms sp3 Configuration2 electrons in 1s and 1 electron in 2s orbital
and each of the three 2p orbitalsCarbon now has 4 electrons to share giving
it a valence of 4Example of Methane with angle between
hydrogen bonds being 109.5o
Chemical BondsChemical Bonds
IonicCrystalCovalentHydrogen (Weak)Van der Waals Forces
ReactionsReactions
Exothermic
Endothermic
OHCOOCH 2224 22
Elementary Composition of Elementary Composition of Body-Dry Weight BasisBody-Dry Weight Basis
Carbon=50% P=2.5% Magnesium=0.1
Oxygen=20% K=1.0% Iron=0.01%
Hydrogen=10% Sulfur=0.8% Mn=0.001%
Nitrogen=8.5% Sodium=0.4% Iodine=0.00005
Calcium=4.0% Chlorine=0.4% Many Others
Organic ChemistryOrganic Chemistry
CHO PrimarilyEthane, Ethylene,AcetyleneBenzeneMethane
IsomersIsomers 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)
Major GroupsMajor 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
Functional Aspect of GroupsFunctional 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
Functional Aspect of Groups-Cont.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
Multifunctional GroupsMultifunctional Groups
Hydroxy Acid R-COH-COOHKeto Acid R-CO-COOHDicarboxylate HOOC-R-COOHPhosphates
– PO4= Pi
– Pyroposphate PPi
– Triphosphate R-P-P-P
Consistancy of Blood Plasma Consistancy of Blood Plasma (Age 40)(Age 40)
Na=136-149 meq/L
Albumin=3.5-5.0 g/dl
Cholesterol (total)=150-260mg/dl
Phenylalanine=0.8-1.8mg/dl
Chloride=118-132 meq/L
Transferrin=220-400 mg/dl
Triglyceride=56-298mg/dl
Iron=50-170ug/dl
Bicarbonate= 18-23 meq/L
Ceruloplasmin=18-45mg/dl
Calcium=8.4-10.2mg/dl
Vitamin A =30-65ug/dl
Protein=6.4-8.3 g/dl
Glucose(fasting)=70-105mg/dl
Glutamine=6-16mg/dl
Vitamin D =14-42 ng/dl
(25-OH)
Animal Cell StructureAnimal Cell Structure Plasma Membrane Nucleus Nucleolus Nuclear Membrane RER SER MTOC (Centrioles) Mitochondria Cytosol Cytoplasm? Golgi Body Vesicles Lysosomes Microsomes
Nucleus
Plant Cell StructurePlant Cell Structure
ChloroplastsCell Wall Starch GranulesEtc.
Plant and Animal Plant and Animal BiochemistryBiochemistry
Plant BiochemistryAnimal Biochemistry
– Animal Science vs. Human Nutrition
StarchesStarches
AmyloseAmylopectinGlycogen
SugarsSugars
Sugars– Monosaccharides
Glucose, fructose, galactose, mannose
– Disaccharides Lactose, sucrose, maltose
– Polysaccharides Glycogen, starch, cellulose
Triose Pentose Hexose
GlycogenGlycogen
Branched Chain Polysaccharide– Approx. every 8 glucose a branch (alpha 1,6)– Bond between glucose (alpha 1,4)
Efficient energy storageMainly liver (also other tissues)
CelluloseCellulose
Relatively Linear – Beta 1,4
Other SugarsOther Sugars
ChitinArabinogalactanOlimeric Proanthocyanidins (OPCs)
DigestionDigestion 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
EnzymesEnzymes
IsomaltaseLactase (-galactosidase)SucraseMaltase
Insulin/Glucagon and Insulin/Glucagon and Glucose-Glucose Glucose-Glucose HomeostasisHomeostasisMain Metabolic Fuels are Glucose and
Fatty AcidsLong 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
If you ate a 3oz. Donut in the If you ate a 3oz. Donut in the morning & assume 100% morning & assume 100% carbohydrate---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
If you ate a 3oz. Donut in the If you ate a 3oz. Donut in the morning & assume 100% morning & assume 100% carbohydrate---carbohydrate---What % of your average daily caloric intake
does this represent?– 1800 Kcal / day (1500-2200)– 340Kcal/1800Kcal X 100 = ~20%
If you ate a 3oz. Donut in the If you ate a 3oz. Donut in the morning & assume 100% morning & assume 100% carbohydrate---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%
If you ate a 3oz. Donut in the If you ate a 3oz. Donut in the morning & assume 100% morning & assume 100% carbohydrate---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
GluconeogenesisGluconeogenesis
Occurs primarily in liverStimulated by epinephrine
Glucose HomeostasisGlucose 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
Alcoholism and HypoglycemiaAlcoholism and Hypoglycemia
Inhibits Thiamine absorption in gutInhibits Lactate Dehydrogenase (Reverse)Liver Pyruvate levels dropHypoglycemic due to inhibited
gluconeogenesis (anabolic)
Alcohol Consumption Alcohol Consumption Continued;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.