Download Medical Biochemistry

Medical Biochemistry
Robert F. Waters, PhD
Overview
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
Metabolism

Anabolism
 Catabolism
 Conversion into derivatives
– e.g histidine to histamine
– Tyrosine to thyroxines
– Tyrosine to melanin
– Choline to acetylcholine
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 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 Review

Inorganic Chemistry
 Organic Chemistry
 Biochemistry
Cations and Anions—Mono,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 Chemistry

Water
– Poiseulles’ Law
(r 2 )( p)( r 2 ) pr 4
Q

nl 8
8nl






Non-compressible
Friction
Diameter associated with area
Pressure
Viscosity (n)
Length (l)
r
2
p  Pout  Pin
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!)
Concentration of Water

1 liter=1000 gm
 18gm/mole
(Gram Equivalent)
– O = 16
– 2H=2

Number of Moles per liter
1000
 55.5m / l
18 gm / mole

Number of Molecules per liter
23
55.5 * [6.02 *10 ]
Example of Number of
Molecules of Oxygen in a
Breath

Example to be completed by student
– Assume 1 liter breath
– Diatomic Oxygen
pH

Hydrogen Ion Concentration
 Dissociation of Water


kw  [ H ][OH ]  1  10


P= - logarithm
pH  pOH  pkw
7 + 7 = 14
 Acidity vs. Alkalinity
 pH in living systems
14
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
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
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

Chemical Bonds

Ionic
 Crystal
 Covalent
 Hydrogen (Weak)
 Van der Waals Forces
Reactions

Exothermic
CH4  2O2 
 CO2  2 H 2O   

Endothermic
Elementary Composition of
Body-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 Chemistry

CHO Primarily
 Ethane, Ethylene,Acetylene
 Benzene
 Methane
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)
Major Groups








R-OH
R-NHx
R-COOH
R-CHO
R-CO-R
R-CH3
R-PO4
R-SH
Hydroxyl
Amino
Carboxyl
Carbonyl (Aldehyde)
Ketone
Methyl
Phosphate
Sulfhydryl
Functional Aspect of Groups






Alkyl
CH3-(CH2)nAlkene
-C=CAromatic
Alcohol
R-OH
Amines
R-NH2
Sulfur Derivatives
– R-SH
Sulfhydryl (Thiol)
– R-S-S-HDisulfide
Functional Aspect of Groups-Cont.

Carbonyl Groups (R-CHO)
– Aldehyde
– Ketone
– Carboxylic Acid
– Ester
– Amide
R-CHO
R-CO-R
R-COOH
R-COO-R’
R-CO-NH2
Multifunctional Groups

Hydroxy Acid
 Keto Acid
 Dicarboxylate
 Phosphates
R-COH-COOH
R-CO-COOH
HOOC-R-COOH
– PO4= Pi
– Pyroposphate
– Triphosphate
PPi
R-P-P-P
Consistancy of Blood Plasma
(Age 40)
Na=136-149
meq/L
Albumin=3.5 Cholesterol
(total)=150-5.0 g/dl
Phenylalanine
=0.8-1.8mg/dl
260mg/dl
Chloride=118- Transferrin=
132 meq/L
220-400
mg/dl
Triglyceride=5 Iron=506-298mg/dl
170ug/dl
Bicarbonate=
18-23 meq/L
Ceruloplasmin Calcium=8.4=18-45mg/dl
10.2mg/dl
Vitamin A
=30-65ug/dl
Protein=6.48.3 g/dl
Glucose(fastin Glutamine=6g)=7016mg/dl
105mg/dl
Vitamin D
=14-42 ng/dl
(25-OH)
Animal Cell Structure














Plasma Membrane
Nucleus
Nucleolus
Nuclear Membrane
RER
SER
MTOC (Centrioles)
Mitochondria
Cytosol
Cytoplasm?
Golgi Body
Vesicles
Lysosomes
Microsomes
Nucleus
Plant Cell Structure

Chloroplasts
 Cell Wall
 Starch Granules
 Etc.
Plant and Animal Biochemistry

Plant Biochemistry
 Animal Biochemistry
– Animal Science vs. Human Nutrition
Starches

Amylose
 Amylopectin
 Glycogen
Sugars

Sugars
– Monosaccharides

Glucose, fructose, galactose, mannose
– Disaccharides

Lactose, sucrose, maltose
– Polysaccharides


Glycogen, starch, cellulose
Triose
 Pentose
 Hexose
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)
Cellulose

Relatively Linear
– Beta 1,4
Other Sugars

Chitin
 Arabinogalactan
 Olimeric Proanthocyanidins (OPCs)
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
Enzymes

Isomaltase
 Lactase (-galactosidase)
 Sucrase
 Maltase
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
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
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%
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%
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
Gluconeogenesis

Occurs primarily in liver
 Stimulated by epinephrine
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
Alcoholism and Hypoglycemia

Inhibits Thiamine absorption in gut
 Inhibits Lactate Dehydrogenase (Reverse)
 Liver Pyruvate levels drop
 Hypoglycemic due to inhibited
gluconeogenesis (anabolic)
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.