Physiologic Chemistry

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Physiologic Chemistry

• Respiratory Care Programs
• Integrated Sciences

2
Cell Structure and Function

• The cell is the fundamental unit of all
  organisms, all of which have certain similarities
• The primary function of any cell is the
  manufacture of proteins.

3
The Cellular Organelles--Micromachines

• Nucleus--the cells brain controls cellular
  activities and holder of chromatin, our genetic
  material
• Mitochondrion--the cells powerhouse, creates
  energy in the form of ATP from either stored or
  consumed foodstuffs
• Centrosome--becomes the central locus for spindle
  fiber attachment during cell division(mitosis).

4
The Cellular Organelles--Micromachines

• Endoplasmic Reticulum--holder of the ribosomes,
  the site of protein synthesis
• Golgi Apparatus--site of waste packaging and
  disposition waste vacuoles are created to hold
  waste for later removal
• Vacuoles--look like openings in cytoplasm, used
  as either nutrient or waste sites

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The Cellular Organelles--Micromachines

• Lysosome--site of enzyme release when the cell is
  in jeopardy
• Cell Membrane--the osmotic barrier surrounding
  the cytoplasmic matrix traversed at different
  intervals by specific transport mechanisms
• Cytoplasmic matrix--contains all cellular
  contents...

6
The Cell--a picture
cytoplasm

• A miraculous machine alone...it produces a wide
  variety of proteins, from enzymes, antibodies, to
  nutrient proteins.

centrosome
ER
GOLGI
Nucleus
Lysosome
Mitochondrion
Cell membrane
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How these cells create energy--an abbreviated
version
The three primary foodstuffs of carbohydrates,
proteins, and fats all enter the Krebs cycle
eventually, even though their respective pathways
are different.

• The key however, is carbohydrate metabolism,
  since in
• many ways it is the center of metabolism.
• First glucose, enters the Embden-Meyerhoff
  pathway
• or glycolysis--this path is anaerobic, glucose
  is broken
• into 2, three-carbon chains, and high energy
  phosphates
• are added (oxidative phosphorylation). The end
  result is
• the production of the intermediate compound
  pyruvate.

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How these cells create energy--an abbreviated
version

• Second, pyruvate triggers the release of the
  enzyme
• system Acetyl CoA catalyzing the continued
  breakdown
• of glucose in the aerobic Krebs Cycle, which the
  3-carbon chain
• moves through twice. Waste products are carbon
  dioxide
• and water.
• Third, hydrogen ions from this process trigger
  the
• cytochrome oxidase system, completing this
  pathway.
• The primary waste product of the cytochrome
  system
• is water.
• The result is the production of 38 ATP, high
  energy
• compounds

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How these cells create energy--an abbreviated
version

• If for some reason however, not enough oxygen is
  available,
• anerobic metabolism will occur, and lactic acid
  and ethanol are
• the resultant waste products.
• Again, glucose metabolism is central to all
  metabolic pathways,
• in part because the brain can only use glucose
  for its energy
• requirements.

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Glucose Metabolism
Glucose 6C
2H 2
O 2
2 ATP
Glycolysis
Cytochrome System
anaerobic
LACTATE ETHANOL
Pyruvate 3C
2 H 2
aerobic
6 H2 O
from NADH2
acetyl Co-A
2CO2
2 ATP 4 CO2
Krebs Cycle
10H2
34 ATP
from NADH2 or FADH2
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Glucose, Protein and Fat Metabolism--an overview
Complex Carbohydrates
Fats
Proteins
Glucose
Fatty acids Glycerol
Glyceraldehyde 3P
Amino acids
Pyruvate
Acetyl Co-A
Urea
Ketoacids
H2O
ATP
Krebs Cycle
CO2
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The Nucleic Acids

• DNA, deoxyribonucleic acid,
• the foundation genetic material.
• It is a double helix (double strand)
• polynucleotide made up of four
• primary amino acid bases--
• Guanine
• Cytosine
• Adenine
• Thymine

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The Nucleic Acids
RNA--Ribonucleic Acid--- also a polypeptide, it
is a single helix made up of four primary amino
acid bases-- Guanine Cytosine Adenine Uracil Ur
acil replaces the amino acid Thymine found in DNA.
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The Nucleic Acids
RNA comes in three forms 1) mRNA -- the amino
acid messenger translated from DNA, carrying the
codes for a specific protein to be produced. 2)
tRNA -- this RNA carries the amino acid (and
codes) for assembly at the ribosome. 3) rRNA
--the RNA of the ribosome, that is responsive
to the mRNA from the nucleus (DNA) and arranges
itself to become much like a cast of the mRNA
codes. When tRNA arrives, the amino acids and
codes of the mRNA are now assembled to create the
protein needed.
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Hemoglobin
A large protein structure having a molecular
weight near 65,000, comprised of 4 heme units and
globin
The globin portion is a protein molecule, made up
of 2 ?? and 2 ??polypeptide chains. Each of
these chains is bound to an iron (heme)
moiety. The iron attaches at a histidine residue
in both the alpha and beta chains.
Hemoglobin is a metalloporphyrin , that is,
porphyrin combined with a metal, in this case,
iron.
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Hemoglobin-a simplified structure
HEME
HEME
GLOBIN
HEME
HEME
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Hemoglobin

• In the life of a human being, 4 different types
  of hemoglobin
• will be produced, all with different globin
  chains
• Embronic Hemoglobin (2????and 2???chains)
• Fetal Hemoglobin or HbF (2 ? and 2 ? chains)
• Normal Adult Hemoglobin or HbA (2 ??and 2 ?
  chains)
• Adult Hemoglobin Variant or HbA2 (2 ? and 2 ?
  chains)

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Hemoglobin-The Oxygen Dissociation Curve
Hb Sat ()
Under normal conditions, only 27 torr PO2 needed
for 50 Saturation!!!!
PO2 in torr
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Hemoglobin--The Oxygen Dissociation Curve
Actually a misnomer, for the curve tells the
story of oxygen loading as well as unloading.
Increased Hemoglobin Affinity for Oxygen--a
left shift of the curve...easy to load
oxygen...difficult to unload Decreased
Hemoglobin Affinity for Oxygen-- a right shift of
the curve...difficult to load...easy to unload
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Hemoglobin--Causes of Right and Left Shifts

• RIGHT SHIFTS
• (Decreased Affinity)
• H
• Body Temperature
• PCO2
• 2,3-Diphosphoglycerate
• Abnormal Hbs such as
• Hb Kansas, Hb Bristol, Hb
• Seattle

• LEFT SHIFTS
• (Increased Affinity)
• H
• Body Temperature
• PCO2
• 2,3-Diphosphoglycerate
• Abnormal Hbs such as
• Hb Chesapeake , Hb Little Rock, Hb Rainier

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Hemoglobin

• Not only an oxygen carrier, it serves as one of
  bloods
• buffering systems.
• When oxygenated, hydrogen ions are released to
  play a
• vital role in lowering pH, helping to reverse the
  carbon
• dioxide reaction so that carbon dioxide can be
  exhaled as
• a free gas.
• When deoxygenated, hydrogen ions (primarily from
• the carbon dioxide reaction), are accepted
  thereby allowing
• the carbon dioxide reaction to proceed
  forward,placing
• carbon dioxide in solution in the form of
  bicarbonate.

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Hemoglobin--reactions at the tissue level
Tissue
Plasma
Erythrocyte
Dissolved
CO2
Dissolved
CO2
CO2
H2O CO2
H2O
capillary membrane
H2CO3
CO2
HCO3- H
HCO3-
Cl-
Cl-
H HbO2
O2 HHb
HHb CO2
O2
O2
Carbamino compounds
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Hemoglobin--reactions at the alveolar level
Alveoli
Plasma
Erythrocyte
Dissolved
CO2
CO2
CO2
Dissolved
H2O CO2
H2O
capillary membrane
H2CO3
CO2
HCO3- H
HCO3-
Cl-
Cl-
H HbO2
O2 HHb
HHb CO2
O2
O2
Carbamino compounds
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Hemoglobin Breakdown Reuse
hemoglobin
Porphyrin ring split w/ open heme complexed
w/globin chains-- VERDOHEMOGLOBIN
Iron atom released
Open porphyrin ring-- BILIVERDIN
Reduction
Iron stored in Liver
BILIRUBIN excreted in bile
BILIRUBIN
LIVER
to liver
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Hemoglobin--Carbon Dioxide

• Attaches to the terminal amine groups of the
  globin chains, not to heme as oxygen does
• The reaction is reversible and is rapid, similar
  to oxygen

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Hemoglobin Myoglobin

• Hemoglobin
• 4 heme units, 1 globin chain
• Dissociation curve sigmoid
• attach 4 molecules O2
• oxygen release lt 60 torr

• Myoglobin
• 1 heme, 1 globin chain
• Dissociation curve--hyperbolic
• attach--1 molecule O2
• oxygen release lt 40 torr

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Oxygen Free Radicals

• We need oxygen to maintain metabolism...but,
  oxygen has its side effects as well
• Oxygen has two unpaired electrons spinning in the
  same direction in its outermost shell
• During its metabolic engagements, oxygen is
  reduced, but some the oxygen may undergo
  univalent reduction--that is it gains one
  electron...
• When this happens, OXYGEN FREE RADICALS ,
  chemical intermediates of oxygen metabolism, are
  formed.

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Oxygen Free Radicals

• Those radicals considered cytotoxic (oxidants)
• O2- --superoxide radical
• 1O2 --singlet oxygen
• OH . -- hydroxyl radical
• .OH2 . --perhydroxyl radical