Water and pH

Water
Hydrogen Bonds in Water
- Dipolar nature of water allows it to form hydrogen bonds
- in H20, the oxygen atom has two unshared electrons that form an electron dense cloud around it
- In the covalent bond formed between the hydrogen and oxygen atoms, the shared electrons are
attracted toward the oxygen atom, thus giving the oxygen atom a partial negative charge and
the hydrogen atom a partial positive charge.

Water as a solvent
- Polar organic molecules and inorganic salts readily dissolve in water because water also forms
hydrogen bonds and electrostatic interactions with these molecules
o The organic molecules which contain a high proportion of electronegative atoms
(usually O and N) are soluble in water because these atoms participate in hydrogen
bonding
- Hydrogen bonds are weak enough to allow movement of water and solutes. The hydrogen
bonds continuously dissociate and reform which permits solutes to move through water and
water to pass through channels in cellular membranes
o Hydrogen bond between water molecules lasts only 10psec (1 picosecond = 10 -12 sec)
o Water molecule in hydration shell stays only 2.4 nsec (1 nanosecond = 10 -9 sec)

Water and Thermal Regulation

- Water has high heat of fusion (the heat you need to remove to solidify)
o The quantity of heat necessary to change 1g of solid to a liquid with no temperature
change
o Solids can be heated to the point where the molecules holding their bonds together
break apart and form a liquid. The most common example is solid ice turning into liquid
water. This process is better known as melting, or heat of fusion, and results in the
molecules within the substance becoming less organized. When a substance converts
from a solid state to a liquid state, the change in enthalpy (ΔH) is positive. However, if
the substance is transforming from a liquid state to a solid state the change in enthalpy
(ΔH) is negative. This process is commonly known as the freezing, and results in the
molecules within the substance becoming more ordered.
- Water has high thermal conductivity
o Materials with a high thermal conductivity can effectively transfer heat and readily take
up heat from their environment
o facilitating heat dissipation from high energy-using areas such as the brain into
the blood and the total body water pool
- High heat capacitiy and high heat of vaporization
- Water responds to the input of heat by decreasing the extent of hydrogen bonding and to
cooling by increasing the bonding betweenwater molecules
Electrolytes
- ECF and ICF contain electrolytes (term applied to bicarbonate HC03 -, and inorganic cations and
anions)
- Na+ and Cl- in ECF
- K+ and HPO4-2 in ICF

Osmolality and Water Movement

- Osmolality is the concentration of solutes
o the osmolality of a fluid is proportionate to the total concentration of all dissolved
molecules, including ions,organic metabolites, and proteins expressed in milliosmoles
mOsm/kg water
- Water will move from low osmolality to high osmolality to achieve equal osmolality on both
sides of a membrane
o Osmotic pressure – the force needed to keep the same amount of water on both sides
of the membrane

Acids
The pH of water
- Review: common logarithm is a logarithm to the base 10
o Logarithm Log10 0.0000001 = -7
o Exponential form 0.0000001 = 10-7
-

Proteins
Enzymes
Catalysis
- Review: Factors that can influence the rate of a chemical reaction:
o Temperature (increased kinetic energy, more frequent collisions)
o Concentration (more reactants packed in given volume, greater chances of reactants
colliding properly)
o Catalysts (lowers activation energy)
- Reminder: activation energy has no connection to whether reaction is SPONTANEOUS (energy
releasing) or NONSPONTANEOUS (energy absorbing)
o Uncatalyzed reaction that is nonspontaneous is still nonspontaneous in the presence of
a catalyst
- Enzyme Reaction
o E + S ⇌ ES → E + P
o KM or the Michaelis constant describes Step 1
o Vmax or the maximum velocity describes Step 2

Cofactors and Coenzymes

 - some enzymes consist ENTIRELY of proteins
- some enzymes have nonprotein portions called cofactors (metal ion; if organic substance
specifically a coenzyme)
o apoenzyme - enzyme lacking its cofactor
o holoenzyme - combination of apoenzyme and its cofactor
o metalloenzyme - apoenzyme and metal ion cofactor
o prosthetic group - tightly bound coenzyme
- enzyme in an inactive form is called proenzyme or zygmogen
- Remember: activation of inactive form of enzyme serves one form of enzyme control:
o Inhibition is another form of control (i.e. competitive and noncompetitive inhibition)

Six Basic Types of Enzymes

Class Class Name Type of reaction catalyzed

no.
1 Oxidoreductases Redox reactions – transfer of electrons (hydride ions or H
atoms)
2 Transferases The transfer groups of atoms
3 Hydrolases Hydrolysis
4 Lyases Additions to a double bond, or the formation of a double bond

(Cleavage of C—C, C—O, C—N or other bonds by elimination,

leaving double bonds or rings, or addition of groups to double
bonds)
5 Isomerases The isomerization of molecules (transfer of groups within
molecues to yield isomeric forms)
6 Ligases or synthetases The joining of two molecules

(Formation of C—C, C—S, C—O, and C—N bonds by

condensation reactions coupled to cleavage of ATP or similar
cofactor)

Enzyme Kinetics
- Enzymes, like all catalysts, catalyze both the forward and the reverse reactions.
- The ultimate equilibrium concentrations of substrate and products are the same whether an
enzyme is present or not; the enzyme merely changes the amount of time necessary to reach
this state.

Rate Determination
- Rate increases until it reaches saturation point (where all enzyme molecules are part of an
enzyme-substrate complex)
- Plot the Reaction rate (V) versus substrate concentration [Substrate]
 - Rate approaches Vmax asymptotically
o Low substrate concentrations, reaction approaches first order kinetics (rate depends on
concentration of one reactant)
 Useful in application of Michaelis-Menten equation
o High concentrations, reactios approaches zero order kinetics (rate is independent of
reactant concentration)
- In an uncatalyzed reaction, increasing the substrate concentration doesn’t lead to a limiting V max.
The rate continues to increase with increasing substrate concentration.
o An indirect evidence of the enzyme-substrate complex: tightly bound grouping of the
enzyme and substrate
o The limit occurs when all enzyme molecules are part of a complex and no free enzyme
molecules are available to accommodate the additional substrate molecules

Michaelis-Menten Equation
V max [ S ]
V=
[ S ] +KM

- An expression relating the catalytic rate (K 2 or Kcat ) to the concentrations of the enzyme and
substrate and to the individual rates was developed
o Examine the enzyme reaction pathway. The various instances of k refer to the rate
constants of various steps

- Start Point: relationship between rate of reaction and concentration of enzyme-substrate

complex
o V = k2 [ES]
- Follow: relationship between rate of ES formation and rate of ES breakdown
o k1 [E] [S] = (k-1 + k2 ) [ES]
o Steady-state assumption: rate of formation of ES must be equal to rate of breakdown of
ES because it is assumed that concentrations of ES remains nearly constant
- Follow: rearrange the previous equation to get the Michaelis constant
[ E ] [S] (k −1+ k 2 )
o [ ES]
= k1
= KM
- KM is a measure of the binding in the enzyme-substrate complex. A high K M value indicates that
the binding is weak, whereas a low value indicates that the binding is strong.
- Km is important in checking the properties of an enzyme
- This value is unique to each enzyme – measure it to determine how that enzyme works relative to
the substrate (Enzyme’s affinity for its substrate)
Enzyme Inhibition and the Michaelis Menten Equation

Allosteric Enzymes
- Michaelis Menten equation does not apply to these kinds of enzymes
- These enzymes exhibit allosteric effect

Maximum reaction Rate

- Reaction’s speed when all of the enzymes are working ( Vmax )
- When the rate reaches this line, substrate concentration can get higher and higher without
affecting the reaction rate

Carbs, Lipids, Nucleic Acids, etc.

Carbohydrates
Properties of Carbohydrates
- Remember: most carbohydrates recognizable by -ose suffix
o Aldose – carbonyl group (C==O) is an aldehyde
o Ketose – carbonyl group is a ketone
- Contain chiral carbons
- Have multiple chiral centers where stereoisomers = 2 n , n = no. of chiral carbons

Monosaccharides
- Most monosaccharides are in the D-form (dextro) rather than L-form (levo)
o Mirror images of each other
o D-form  OH on the right in open form
o L-form  OH on the left in open form
- Pyranose and furanose forms are anomers (cyclic forms)
o Pyranose – five and a nOse
o Furanose – four and a nOse
- Cyclic hemiacetal groups undergo continuous change in solution
o Mutarotation is the process of converting back and forth from an α anomer to the open
form to the β anomer
- After a glycosidic bond forms, the ring is “locked” meaning it won’t reopen and mutarotation no
longer takes place

Derivatives of Monosaccharides
o deoxy sugars – hydrogen atom replaces one or more of the –OH groups
 o amino sugars – an –OH group of a monosaccharide has been replaced by an amino –NH 2 group
o alcohol sugars – carbonyl group of a monosaccharide has been reduced to an alcohol
 lose the double bond with oxygen and gain a hydrogen
o carboxylic acid sugars – an aldehyde or alcohol group of a monosaccharide has been oxidized to
form a carboxyl group –COOH
o esters – monosaccharides may react with acids to form esters
 example: combine them with phosphoric acid

Reactions of Monosaccharides
Remember: monosaccharides contain alcohol and aldehyde or ketone groups
o Reduction – when a carbon-oxygen double bond of an aldehyde or ketone is treated with H 2 and
catalyst platinum (Pt) or encounters the appropriate enzyme, it is reduced to an alcohol
o Oxidation – when aldehyde or alcohol groups oxidize and produce carboxylic acid sugars
o In nature, these oxidations are catalyzed by enzymes
o Benedict’s reagent oxidizes aldehydes but not alcohols
o Reducing sugars – sugars that give a positive Benedict’s test (react with Benedict’s
reagent) reduce Cu2+ present in the reagent
o Exceptions: fructose and many other ketoses are also reducing sugars even though
ketones are not oxidized by Benedict’s reagent
 They (ketoses) rearrange to become aldoses, each of which is a reducing sugar
o Hemiacetal Formation
o Carbonyl group of aldehyde or ketone reacts with hydroxyl group of an alcohol
o A hemiacetal carbon atom is one that is attached to –OH and –OC
 An acetal is one in which a carbon atom is attached to two –OC groups

Oligosaccharides
- These are formed when 2 to 10 monosaccharide residues are joined to one another by glycosidic
bonds
o See page 410 Ch 12.4 Oligosaccharides (in Integrated Chem) for an example of
combining two monosaccharides i.e. maltose
- Simplest and most common are disaccharides

Disaccharides
- Maltose
o Combination of two D-glucose molecules
o Alpha (14) glycosidic bond
- Cellobiose

- Lactose
 - Sucrose (table sugar)
o Double headed arrow is used because each monosaccharide supplies a hemiacetal
group to the glycosidic bond
o Not a reducing sugar – no hemiacetal group and is unable to mutarotate

Glycolipids
- Sugar containing lipids present in nerve cell membranes
- Mono-, oligo-, polysaccharide attached to alcohol group of lipid by a glycosidic bond

Indigestible oligosaccharides
- When a lactose-intolerant person consumes dairy products, the lactose is metabolized by
intestinal bacteria instead of by β-galactosidase. This results in the production of gases such as
 CO2, H2, and CH4, which cause bloating. Small carboxylic acids that also form cause diarrhea by
drawing water into the intestines through osmosis.

Lipids
Fatty Acids
- Saturated (single bonds to carbon) – solids at room temp
- Unsaturated (contains double bond/s to carbon) – liquid at room temp (25c)
o Monounsaturated (one C=C double bond)
o Polyunsaturated (more than one C=C double bond)

- Fatty acids as anions

o Reacting with NaOH changes the solubility of the fatty acid
o They consist of Na+ and fatty acid anion (carboxylate anion) where the oxygen has a 1—
charge
- Fatty acid structure and melting point
o Longer hydrocarbon tail, stronger interaction of molecules through London dispersion
froces
o Stronger London forces, higher temperature required for melting
o More cis double bonds, more farther apart the hydrocarbon tails resulting to weaker
London force and lower melting point

Waxes
- Combination of fatty acid and a long chain of alcohol
Triglycerides (or triacylglycerides)
- Three fatty acid residues are joined to a glycerol residue by ester bonds

Reactions of Triglycerides
- Reduction
o C=C double bonds in unsaturated triglycerides can undergo reduction with H 2 and Pt
o Partial hydrogenation – example is when vegetable oil is treated with H 2 and Pt but the
reaction is stopped before all of double bonds have been removed
 having fewer double bonds, oil will not spoil (oxidize) as rapidly
- Oxidation
- Saponification
o Hydrolysis of ester groups in the presence of OH—
o Glycerol and fatty acid salts (soap) are produced
o Quality of the products depend on (1) source of OH— and (2) degree of unsaturation in
the triglyceride
Trans Fats
- When unsaturated vegetable oils are partially hydrogenated some of their cis-double bonds are
converted to the trans stereoisomer
- Diets high in trans fats have been linked to lowered HDL levels, increased risk of heart disease,
and changes in membrane structure
- Important ! some food contain natural trans fats

Phospholipids
- Phosphate ion (PO43- )
- Glycerophospholipids (also known as phosphoglycerides) – combining glycerol, 2 fatty acids, 1
phosphate ion, and 1 alcohol containing compound
o Plasmalogens – first carbon of glycerol has hydrocarbon chain attached via ether linkage
(more resistant to chemical attacks); membranes of muscles and nerves
o Phosphotidates – the sample below is a phosphotidate

- Sphingolipids – sphingosine replaces glycerol and 1 fatty acid

o Sphingosine – an 18-carbon amino alcohol with an unsaturated hydrocarbon chain
Glycolipids
- Lipids that contain sugar residue which is in most cases attached to a sphingosine backbone

- Cerebrosides – glycolipid using simple sugars (one ring); found at nerve synapses
- Gangliosides – made using chain of simple sugars; nerve membranes
o the sugar in some gangliosides help determine blood type
Use of Lipids in Membranes
- the lipid bilayer
- membranes may contain 20-80% protein; can be peripheral (surface) or integral (extends into or
through the membrane)

Membrane transport
- pump (active transport against concentration gradient)
o generic name: P-type ATPase (because phosphate from ATP is transferred to an
intermediate)
o example: Na+ - K+ pump which generates and maintains high potassium ion and low
sodium ion concentration (rel. to extracellular environment)
 3 Na+ ions out
 2 K+ ions in
o Note ! not all pumps require hydrolysis of ATP to supply energy
 Cotransporters
 Symporters (same direction) or antiporters (opposite)
- channels
o highly selective
o regulating from open to closed state
 voltage-regulated gate (chemical potential)
 ligand-gated (specific chemicals)
o example: acetylcholine receptor (nerve impulses)
 ACh attaches to receptors, opening the channel
 Leads to inward sodium ion diffusion and outward potassium ion diffusion
 Change in concentrations transmits nerve impulse into the second nerve cell

Steroids
 o Lipids that share basic fused ring structure – three 6-carbon atom rings and one 5-carbon atom
ring
o Includes cholesterol, steroid hormones, bile salts

Cholesterol
- Somewhat amphiphatic
- Transported as suspensions by lipoproteins because not freely soluble in water
o Low density lipoproteins (LDL) – transport cholesterol and phospholipids from liver to
cells
o High density lipoproteins (HDL) – transport cholesterol and phospholipids from cells
back to the liver

Eicosanoids
- Hormones derived from arachidonic acid and other essential 20-carbon fatty acids (eicos means
20)
- When hydrolyzed, arachidonic acid transforms into
o Prostaglandins – all contain five-carbon ring; part of the inflammatory response system
o Thromboxanes
o Leukotrienes – three conjugated double bonds (triene); associated with allergy attacks

Nucleic Acids
Building blocks of nucleic acid
Nucleic acids consist of chains of nucleotide residues. Nucleotides contain a monosaccharide, phosphate,
and a base.

- Phosphoric acid
o ability to form phosphate esters when phosphate ion reacts with alcohol
- Monosaccharide
o provides alcohol group to form phosphate esters
o formation of N-glycosides when hemiacetal group reacts with an amine
 review ! glycosides form when hemiacetal group reacts with hydroxyl group

- Organic base
o Purines
o Pyrimidines (hexagon shape)
 Thymine only in DNA
 Uracil in RNA
What do we mean when we say nucleosides?
- When ribose or 2-deoxyribose is combined with a purine or pyrimidine base, a nucleoside is
formed
- a βN-glycosidic bond involving carbon 1’ of the monosaccharide and one of the nitrogen atoms
in the base (nitrogen atom 1 of pyrimidines and nitrogen atom 9 of purines)
What do we mean when we say nucleotides?
- When phosphate ion reacts with one of the OH groups on the sugar residue of a nucleoside to
form a phosphate monoester, a nucleotide is produced
- A nucleotide is a nucleoside monophosphate – a nucleoside residue and a phosphate residue
joined by a phosphoester bond
What are nucleoside diphosphates? Nucleoside triphosphates? Cyclic nucleotides?
- Nucleoside diphosphate is generated when a 2nd phosphate attaches to the first; nucleoside
triphosphate formed in addition of 3rd phosphate
o The connection between phosphate groups is called a phosphoanhydride bond
o Think adenosine triphosphate
- Cyclic nucleotides where one phosphate residue has two phosphoester connections to the same
monosaccharide residue
o Help regulate biochemical processes (e.g. effectors for allosteric enzymes)

What are polynucleotides?

- More than 10 nucleotide residues are joined to one another by 3’, 5’ -phosphodiester bonds
- Phosphate residue is attached at the 3’ position of one nucleotide reside and the 5’ position of
another

DNA STRUCTURE
Human DNA contains 3 billion paired deoxyribonucleotide residues and carries an estimated 25,000
genes (stretches of DNA that carry codes for protein production).

- Primary structure: sequence of nucleotide residues

- Secondary structure: helix formed by the interaction of two DNA strands
o Antiparallel arrangement
 o Complementary base pairing
- Tertiary structure: supercoiling or double helices being twisted into tighter, more compact
shapes
o Complex structure of DNA in plants and animals
 Interaction between histones and phosphate group of DNA backbone
o The DNA double helix is wrapped around a group of histones to form a nucleosome
o the strands of DNA that connect the nucleosomes twist further to produce a coiled
structure called chromatin
 Prior to cell division, each chromatin molecule coils and folds to become a
chromosome.

Vitamins
Water Soluble
Vitamin C
B Complex

Fat Soluble
Vitamin A
Vitamin D
Vitamin E
Vitamin K

Hormones
Hormonal Action
Second-messenger hypothesis
- Polypeptide and amine hormones

Steroidal hormonal action

- Steroids

Bioenergetics and Pathways

Life and Energy
Metabolism
- All the processes involved in maintaining a cell which involve energy
o Endergonic (absorbs energy, nonspontaneous)
o Exergonic (produces energy, spontaneous)
- Catabolism  big to small; breaking down of molecules
- Anabolism  small to big; building up of cells

Adenosine Triphosphate (ATP)

- Product of the common catabolic pathway
- 1/10 pound ATP (0.10 lb) present at any one time in the body
- ATP is recycled 1,400 times each day to meet >140 pounds/day requirement for an adult

Free energy content (G)

- (G) is the intrinsic energy present in a molecule
- ∆G is the change in energy (products – reactants)
- If positive ∆G  nonspontaneous, endergonic, requires energy
- If negative ∆G  spontaneous, exergonic, releases energy

Remember: Spontaneity bears no relation to speed. Spontaneous reactions may be very rapid or
very slow.
 ∆G° is the “ideal” or standard value of ∆G
- If ∆G°’ (modified ∆G using biologically more realistic value of pH=7 instead of standard pH=0