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Section 2 Chemical and Biologic Foundations of Biochemistry
Chapt. 4. Basics of Biochemistry
Student Learning Outcomes:
• Describe the importance of water - solvent of life
• Explain the pH of a solution, and the reason
maintenance of pH, and hydration is so critical
• Describe some strong acids and bases and their
dissociation in water
• Describe some key metabolic acids and bases
• Describe typical buffers in biological systems
• (much more later in Physiology)
4. Homeostasis and maintenance of body pH
Maintenance of body pH is
critical:
• 13-22 mol/day of acid produced
from normal metabolism
• Buffers maintain neutral pH
• CO2 is expired through lungs
• NH4+ and ions are excreted
through kidneys
Fig. 4.1
Water
Hydrogen bonds in water
Hydrogen bonds:
Fig. 4.4:
• ~ 60% of body is water
• Dipolar nature makes H2O good
solvent; unequal sharing of e-
A. H bonds
B. Hydration shells
around ions
• bathes cells
• H bonds are weak (5% of covalent)
Water is solvent of life:
• transports compounds in blood
• separates charged molecules
• Dynamic lattice; thermoregulation
(Sweat cools)
• dissapates heat
• participates in chemical
reactions
Fig. 4.2 Fluid compartments
in typical 70-kg man
Fig. 4.3
1
Electrolytes
Osmolality and water movement
Table 4.1 Ions in Body Fluids
ECF mmol/L
ICF mmol/L
Cations
Na+
K+
145
4
12
150
Anions
ClHCO3inorganic phosphate
105
25
2
5
12
100
• Cell membrane semi-permeable
• H2O moves from its high conc to its low
(or from low solute -> high)
Ex. Water from blood to urine
to balance excretion of ions
Ex. Hyperglycemia:
high sugar in blood
pulls water from cells
Energy-requiring transporter (Na+/K+ ATPase)
maintains the Na+/K+ gradient
II. Acids and bases
Table 4 Acids in blood of person
Review Acids and Bases:
• Acids donate H+ (proton)
• Bases (like OH-) accept H+
Fig. 4.5
[H+];
pH = -log
acidic < pH 7; basic > pH 7
in pure H2O, [H+] = 10-7 mol/L = pH of 7
Kd = [H+] [OH-]/ [H2O];
Water distributes between compartments
• Acccording to osmolality
(concentration of dissolved molecules mOsm/kg H2O)
but [H2O] ~ constant
Kw = [H+] [OH-] = 1 x 10-14
increase [H+] -> decrease [OH-],
& vice versa
Acid
anion
Sulfuric (H2SO4)
SO42-
pKa
completely
dissociated
source
dietary aa
Carbonic acid
(R-COOH)
R-COO-
3.8
CO2 from TCA
Acetic acid
(R-COOH)
R-COO-
4.76
ethanol metab
Acetoacetic acid
(R-COOH)
R-COO-
3.62
fatty acid oxid
ketone bodies
Ammonium ion
(NH4+)
NH3
9.25
diet N-containing
2
Acids
Strong acids dissociate completely;
Weak acids dissociate partially – depends on pH
Fig. 4.6:
HA <-> A- + H+
Acid ends in -ic,
Conjugate base
ends in -ate
Henderson-Hasselbalch equation
Ka, equilibrium constant for dissociation of weak acid:
describes tendency of HA to donate H+
HA <-> A- + H+
Ka = [H+] [A-] / [HA]
Higher Ka = greater tendency to donate:
acetic acid Ka = 1.74 x 10-5
NH4+ = 5.6 x 10-10
Ketone bodies
are weak acids
Henderson-Hasselbalch equation
Henderson-Hasselbalch equation describes
relationship between pH of a solution, Ka of acid and
extent of its dissociation
pKa = negative log of Ka
For weak acid HA: pH = pKa + log [A-]/[HA]
a weak acid is 50% dissociated at pH = pKa
[HA] = [A-]
Acids with pKa of 2 are stronger than those pKa of 5:
much more is dissociated at any pH
Buffers resist changes in pH
Buffers resist changes in pH
within ~ 1 pH unit of pKa
Acetic acid:
pH = pKa = 4.76;
50% dissociated:
[A]: [HA] = 1:1
pH 3.76: [A-]: [HA] = 1:10
(not much A- left to
receive more H+)
Fig. 4.7
3
Metabolic buffers
Bicarbonate buffer
Buffers maintain body pH in narrow ranges:
despite huge amounts of acid produced/ day
Blood:
Bicarbonate is metabolic buffer;
• Acid derived from CO2 produced by
fuel oxidation in TCA cycle
• Reacts to form H2CO3
• Weak acid, dissociates to HCO3• Respiration rate can be adjusted to
modify/ in response to pH of blood
pH 7.36-7.44
Intracellular: pH 6.9-7.4
Beating heart: pH 6.8-7.8
Major acid is CO2 from TCA cycle
Metabolic buffers: Bicarbonate-carbonic acid (ECF)
Hemoglobin (rbc), proteins (cells and plasma)
• pH blood = 6.1 + log[HCO3-]/ 0.03 PaCO2
where HCO3- = mEq/ml;
PaCO2 partial pressure arterial blood (mm Hg)
Phosphate in all cell types
(much more later in Physiology)
Biological buffers maintain pH
Fig. 4.8
Urinary hydrogen, ammonium and phosphate
Buffering systems in body:
• Bicarbonate and H+ from dissolved CO2 in rbc
• H+ buffered by Hemoglobin (Hb) and PO4-2
• HCO3- in blood buffers H+ from metabolic acids
• Other proteins (Pr) also buffer; e.g., albumin in blood
Nonvolatile acid is excreted in urine:
• H+ is often excreted as an undissociated acid
• Urine has pH 5.5 to 7
• Inorganic acids include phosphate, NH4+,
• Organic acids are citric, uric
• Sulfuric acid from S in proteins, other compounds
• NH3 is major buffer (NH3 + H+ <-> NH4+)
NH3 is toxic to neurons;
NH4+ is generated in kidney
Fig. 4.9
4
Homeostasis requires fluid balance
Fluid balance is critical for
homeostasis:
Dehydration if salt and water
intake < combined rates of
renal and extrarenal loss
Even if fasting, urinary water
dilutes solutes and ions;
expired air loses water.
Hormones help monitor blood
volumes, osmolarity
Key concepts
Key concepts:
• Water is the basis of life – 60% of body – H bonds
•
• Compounds dissolved in water act as acids, bases
•
Di Abetes: type I diabetes (IDDM) – autoimmune
destruction of β-cells of pancreas
ketoacidosis from blood ketoacids, lowers pH
respiration increases to compensate somewhat
increase urine to dilute blood glucose;
Hyperventilate can give alkalosis in normal person;
Acids release H+, bases accept H+
• Homeostasis requires neutral pH ([H+]), proper
amount of body water
• Buffers resist changes of pH if H+ or OH- added:
• Physiological buffers: bicarbonate, phosphate
• Normal metabolism generates acids and CO2
•
Clinical comments
Intracellular and extracellular (interstitial, blood, lymph)
CO2 + water -> carbonic acid -> bicarbonate and H+
Chapt 4. Review questions
Chapter 4 Review questions:
2. Which of the following is a universal property of buffers?
a. buffers are composed of mixture of strong acids and
strong bases
b. buffers work best at pH at which they are completely
dissociated
c. buffers work best at the pH at which they are 50%
dissociated
d. buffers work best at one pH unit lower than the pKa
e. buffers work equally well at all concentrations.
5
Chapt. 5 Major compounds of the Body
Chapt. 5 Structures of Major Compounds
Biological compounds
Organic molecules of body have C, H, O, N, S, P:
Student Learning Outcomes:
• Describe structures, functions of major biological
compounds:
• Carbohydrates have C, H, O
• Lipids have fatty acids and glycerol (triglycerides)
• Other lipids are phosphoacyglycerols, cholesterol
• Nitrogen compounds include amino acids,
purines and pyrimidines, nucleosides
Carbon is the basis:
• Can do 4 covalent bonds
• Aliphatic
• Aromatic
Naming for number of C,
type of linkage
Fig. 5.1
Functional groups
Functional groups dictate reactivities of molecules –
especially C-O, C-N, C-S bonds
(C- H and C-C less reactive); oxidation state of C important
Reduced vs. oxidized
Reduced and oxidized state of carbon:
Number of electrons around C:
• In Reduction, molecule gains e- and H+;
• In Oxidized state, loses H or gains O
Reduced oxidized
CH4 most reduced
Fig. 5.2
6
Acidic and amino groups
Reactivities of functional groups
Functional groups include:
• Acidic release
• Amine gain
H+
H+
->
Fig. 5.3
Carboxyl C δ+ is very
reactive, attracts δ-:
-O-
-> -NH3+
Acid + alcohol = ester
Fig. 5.4
Acid + amine = amide
(like peptide bond)
• unequal sharing
• polar
Fig. 5.5
Phosphate + alcohol =
phosphoester,
(phosphodiester)
Fig. 5.7
Carbohydrates
Stereoisomers
Carbohydrates: (C H2 O)n
Asymmetric Carbon:
defines D and L sugars
• Nomenclature for C
• Aldehyde vs. ketone
• Polar molecules
• Very soluble in water
Fig. 5.8
Fig. 5.9
Fig. 5.6
Stereoisomers of
monosaccharides C6H12O6
Fig. 5.10, 11
• Phosphate makes
• more polar, keeps in cell
7
Ring forms of sugars in aqueous solution
Substituted sugars
Sugars form ring structures
in aqueous solution: C=O
reacts with other -OH
Sugars can have substitutions:
-NH2, -PO4,
Can convert α -> β forms
Oxidized has COOReduced has H, or only OH
Enzymes specific for each form
Figs. 14, 15
Fig. 5.12, 13
Polysaccharides (Cooper cell biol)
Glycosidic bonds join sugars
Glycogen: storage in
Sugars join in glycosidic bonds:
animal cells
N- or O-linked
Starch: storage in plant
cells
α or β –OH of C1
Cellulose plant cell wall.
glucose, β configuration.
β(1→4) linkages form ->
long chains that pack to
form fibers
Fig. 5.16
8
Lipids
Fatty acids
Fatty acids are simplest lipids: long hydrocarbon
Lipids have 3 main roles:
chains (16 or 20 C) with (COO−) at one end.
Hydrocarbon chain is hydrophobic
– Energy storage
– Major components
of cell membranes
Saturated fatty acids:
no double bonds.
– Important in cell signaling:
steroid hormones, messenger molecules
Unsaturated fatty acids:
one or more
double bonds
(kink structure)
Fig. 5.1 Cooper Cell Biology
Fatty acids
Fats – acyglycerols
Fats = triacylglycerols =
triglycerides: 3 fatty acids, glycerol
Fatty acids are
saturated (solid)
or unsaturated
(fluid)
Phosphoacylglycerols =
2 fatty acids, glycerol, PO4-
Nomenclature:
Fig. 5.18
Cis- (natural) vs
trans- from
artificial
hydrogenation of
polyunsat f.a.
Fig. 5.17
Fig. 5.19
9
sphingolipids
Steroids cholesterol
Sphingolipids = serine + 2 fatty acids
Sphingosine = serine + palmitate
Ceramide = fatty acid + sphingosine
Gangliosides = sugar + sphingolipid
Steroids have 4 ring structure:
• Not very water soluble
Cholesterol is precursor for others:
Sex hormones
Bile salt cholic acid is soluble
Sphingomyelin:
component of
cell membranes,
myelin sheath
Fig. 5.20
Amino acids
Fig. 5.21
Nitrogen bases
Amino acids have –NH2
-COOH
Humans only Lα-aa in proteins (Fig. 5.22)
(Bacteria have D-aa in cell walls)
Fig. 5.22
Nitrogen-containing ring structures
(heterocyclic rings, nitrogenous bases):
N on ring can form H bonds with other molecules
Purines:
A and G
Pyrimidines: T, C and U
Pyridines: - vitamins nicotinic acid (niacin)
pyridoxine (vitamin B6)
Fig. 5.23
neurotransmitter
10
nucleosides
• Bases are linked to sugars form nucleosides.
• DNA has sugar 2′-deoxyribose, RNA has ribose.
• Nucleotides have one or more phosphate groups
linked to 5′ carbon of sugars.
The Molecules of Cells
Important nucleotides: adenosine 5′-triphosphate
(ATP), principal form of chemical energy
Some (e.g., cyclic AMP) act as signaling molecules
within cells.
ATP
Cooper Cell Biology
Compare dATP to ATP
Tautomers
cAMP
Key concepts
Tautomers in N-containing rings are alternate forms,
can have different properties, reactivities:
Ex. Uric acid forms Na-urate crystals in gout
Acidic urine can precipitate uric acid (kidney stone)
Key concepts:
Carbohydrates [sugars, (CH2O)n];
asymmetric carbon, carbonyl, linkages of sugars
Lipids are not very water soluble (hydrophobic):
triacylglcerol, phosphoacylglycerol, cholesterol
Nitrogen-containing compounds:
amino acids, purines, pyrimidines, pyridines
nucleosides, nucleotides
Glycoproteins and proteoglycans - sugars and proteins
Fig. 5.24
11
Figure 2.33 A protein interaction map of Drosophila melanogaster
Clinical comments
Lotta Topaigne – gouty arthritis:
urate from breakdown of G and A, precipitates with Na+
phagocytosed by white blood cells; inflammatory reaction
Di Abietes – diabetic detoacidosis (DKA)
measure blood glucose, ketone bodies
Review questions:
• Diagram the structure of a phospholipid and a fat
• What are the major functions of fats and
phospholipids in cells?
• Diagram the structure of D-glucose, ribose and
dexoyribose in ring form
• Diagram the structure of a disaccharide
12