Department of Biochemistry & Molecular Biology

Federal University Dutsin-Ma

COURSE CODE: BCH 202

COURSE TITLE: General Biochemistry

Topic : (WATER)

CREDIT UNITS: 2 Units

COURSE LECTURER: Dr. Balkisu Abdulrahman

 WATER AS A UNIVERSAL SOLVENT
Water is the predominant chemical component of living organisms. Its unique physical properties,
which include the ability to solvate a wide range of organic and inorganic molecules, derive from
water’s dipolar structure and exceptional capacity for forming hydrogen bonds. The manner in
which water interacts with a solvated biomolecule influences the structure of each. An excellent
nucleophile, water is a reactant or product in many metabolic reactions. Water has a slight
propensity to dissociate into hydroxide ions and protons. The acidity of aqueous solutions is
generally reported using the logarithmic pH scale.
Water is a dipole, a molecule with electrical charge distributed asymmetrically about its structure.
The strongly electronegative oxygen atom pulls electrons away from the hydrogen nuclei, leaving
them with a partial positive charge, while its two unshared electron pairs constitute a region
of local negative charge. Water, a strong dipole, has a high dielectric constant. Its strong dipole
and high dielectric constant enable water to dissolve large quantities of charged compounds such
as salts.

Tetrahedral geometry of water molecule.

WATER AS A NUCLEOPHILE IN METABOLIC REACTIONS
Metabolic reactions often involve the attack by lone pairs of electrons on electron-rich molecules
termed nucleophiles on electron-poor atoms called electrophiles. Nucleophiles and electrophiles
do not necessarily possess a formal negative or positive charge. Water, whose two lone pairs of
sp3 electrons bear a partial negative charge, is an excellent nucleophile. Other nucleophiles of
biologic importance include the oxygen atoms of phosphates, alcohols, and carboxylic acids; the
sulfur of thiols; the nitrogen of amines; and the imidazole ring of histidine. Common electrophiles
include the carbonyl carbons in amides, esters, aldehydes, and ketones and the phosphorus atoms
of phosphoesters. Nucleophilic attack by water generally results in the cleavage of the amide,
glycoside, or ester bonds that hold biopolymers together. This process is termed hydrolysis.
Conversely, when monomer units are joined together to form biopolymers such as proteins or
glycogen, water is a product, as shown below for the formation of a peptide bond between two
amino acids.

MEDICAL AND BIOLOGICAL IMPORTANCE OF WATER

1. Water is an essential constituent of all forms of life.
2. Water is present in every cell. It is the medium in which all cellular events occur.
3. It is required for enzyme action and for the transport of solutes in the body.
4. Water aids the folding of biomolecules like proteins, nucleic acids etc.
5. Semi-fluid nature of body is due to water.
6. Water regulates body temperature.
7. Water accelerates biochemical reactions by providing ions.
8. Water content in the body alters in dehydration and edema

Total Body Water (TBW)

• TBW refers to the total amount of water present in the human body.
• Accounts for 50-70% of body weight, depending on age, sex, and fat composition.
• TBW is divided into two main compartments:

A. INTRACELLULAR FLUID (ICF).This compartment constitutes two-thirds of total body

water and provides the environment for the cell. The most abundant electrolyte in intracellular
fluid is potassium. Intracellular fluids are crucial to the body’s functioning. In fact, intracellular
fluid accounts for 60% of the volume of body fluids and 40% of a person’s total body weight

B. EXTRACELLULAR FLUID (ECF)

This compartment contains about one-third of total body water and is distributed between the
plasma and interstitial compartments. Extracellular fluids can be further broken down into various
types. The first type is known as intravascular fluid that is found in the vascular system that consists
of arteries, veins, and capillary networks. Intravascular fluid is whole blood volume and also
includes red blood cells, white blood cells, plasma, and platelets. Intravascular fluid is the most
important component of the body’s overall fluid balance. The most abundant electrolyte in
extracellular fluid is sodium. The body regulates sodium levels to control the movement of water
into and out of the extracellular space due to osmosis. The extracellular fluid is a delivery system.
It brings to the cells nutrients (eg, glucose, fatty acids, amino acids), oxygen, various ions and trace
minerals, and a variety of regulatory molecules (hormones) that coordinate the functions of widely
separated cells. Extracellular fluid removes CO2, waste products, and toxic or detoxified materials
from the immediate cellular environment.
 Distribution of Total body water

The internal environment is rich in K+ and Mg2+, and phosphate is its major anion. Extracellular
fluid is characterized by high Na+ and Ca2+ content, and Cl− is the major anion. Note also that the
concentration of glucose is higher in extracellular fluid than in the cell, whereas the opposite is
true for proteins. It is thought that the primordial sea in which life originated was rich in K+ and
Mg2+. It therefore follows that enzyme reactions and other biologic processes evolved to function
best in that environment—hence the high concentration of these ions within cells. Cells were faced
with strong selection pressure as the sea gradually changed to a composition rich in Na+ and Ca2+.
Vast changes would have been required for evolution of a completely new set of biochemical and
physiologic machinery; instead, as it happened, cells developed barriers— membranes with
associated “pumps”—to maintain the internal microenvironment.

Electrolytes

Charged solutes or electrolytes are present in body fluids like intracellular fluid (ICF), extra
cellular fluid (ECF), various secretions, blood plasma and bone. The two types of solutes present
in body are inorganic and organic. The inorganic solutes or electrolytes consist of cations and
anions. The organic electrolytes are mainly anions. The inorganic cations are sodium (Na+),
potassium (K+), calcium (Ca2+) and magnesium (Mg2+). The inorganic anions are chloride (Cl–),
bicarbonate (HCO3–), phosphate (PO43–) and sulphate (SO42–). The organic anions are contributed
by proteins, organic acids and organic phosphates.

Medical and biological importance of Electrolyte

1. Physiological processes like membrane potential, neuromuscular excitability, nerve impulse

transmission, HCl secretion and gas transport are dependent on ICF and ECF electrolyte
composition.

2. Blood clotting, enzyme catalysis, bone formation and muscle contraction are dependent on
electrolytes.
Distribution of electrolytes

Sharp differences in the distribution of anions and cations in the ICF and ECF exist. Na+ is the
major cation of extracellular fluid whereas K+ predominates in ICF. Similarly, Cl is the major
anion in ECF whereas organic anions predominate in ICF. Concentrations of electrolytes in ICF
and ECF are given below :

Table 1: Comparison of the mean concentrations of various molecules outside and inside a
mammalian cell.

Electrolytes of blood plasma : The important anions in blood plasma are bicarbonate, chloride,
phosphate, sulfate, iodide and fluoride.
Potassium : Potassium is the most abundant cation of the ICF and is the greatest determinant of
intracellular osmolarity and cell volume. Along with sodium, it produces the resting membrane
potentials and action potentials of nerve and muscle cells Potassium is as important as sodium to
the Na+-K- pump and its functions of cotransport and thermogenesis (heat production). It is an
essential cofactor for protein synthesis and some other metabolic processes. Its level ranges from
3.8-5.4 meq/L. Its level also decreases in vomiting and diarrhoea.
Sodium : Sodium is one of the principal ions responsible for the resting membrane potentials of
cells, and the inflow of sodium through gated membrane channels is an essential event in the
depolarization that underlies nerve and muscle function. Sodium is the principal cation of the ECF;
sodium salts account for 90% to 95% of its osmolarity. Sodium is therefore the most significant
solute in determining total body water and the distribution of water among fluid compartments.
Sodium gradients across the plasma membrane provide the potential energy that is tapped to
cotransport other solutes such as glucose, potassium, and calcium. The Na_-K_ pump is an
important mechanism for generating body heat. Sodium bicarbonate (NaHCO3) plays a major role
in buffering the pH of the ECF-146 meq/L. Its level decreases in vomiting and diarrhoea.

Bicarbonate : Normal plasma bicarbonate level is 24-30 meq/L. It is responsible for the
maintenance of blood pH. It is a component of carbonic acid bicarbonate buffer system. Plasma
bicarbonate level undergoes changes in acid base and electrolyte disturbances.

Chloride : It is the major anion in plasma. The normal range is 100-110 meq/L. It is required for
maintenance of water distribution between plasma and cells. Chloride ions are the most abundant
anions of the ECF and thus make a major contribution to its osmolarity. Chloride ions are required
for the formation of stomach acid (HCl), they play a major role in the regulation of body pH.
Chloride is the major extracellular anion. About 70% is in the extracellular fluid. The average
content of the human body is 35 mEq/kg. Chloride in food is almost completely absorbed. Plasma
levels of Na+ and C1- in general undergo parallel alterations. Chloride ion is strongly attracted to
Na+, K+, and Ca2+ It would require great expenditure of energy to keep it separate from these
cations, so Cl- homeostasis is achieved primarily as an effect of Na+ homeostasis—as sodium is
retained or excreted, Chloride ion passively follows Chloride level decreases in vomiting and
diarrhoea.

Phosphate : Normal phosphate level in plasma ranges from 2-4 mg/dl. It is involved in
maintenance of plasma pH. Phosphates are relatively concentrated in the ICF, where they are
generated by the hydrolysis of ATP and other phosphate compounds. They are a component of
nucleic acids, phospholipids, ATP, GTP, cAMP, and related compounds. Every process that
depends on ATP depends on phosphate ions. Phosphates activate many metabolic pathways by
phosphorylating enzymes and substrates such as glucose. They are also important as buffers that
help stabilize the pH of the body fluids.

Calcium : Normal plasma range is 9-11 mg/dl. Its level decreases in rickets. Calcium lends
strength to the skeleton, activates the sliding filament mechanism of muscle contraction, serves as
Second messenger for some hormones and neurotransmitters, activates exocytosis of
neurotransmitters and other cellular secretions, and is an essential factor in blood clotting. Cells
maintain a very low intracellular calcium concentration because they require a high concentration
of phosphate ions.

Maintenance of electrolyte balance

1. For normal function of body electrolytes concentrations of body fluids must be controlled. Many
mechanisms operate to control body electrolyte balance. One such mechanism is sodium pump. It
maintains a low intracellular level of Na+ and high extracellular level. Hormone aldosterone
maintains electrolyte balance by acting on kidney. It increases Na+ absorption and K+ excretion by
kidney.
2. Diet, water and salt intake influences the concentration of electrolytes in body fluids.
3. Kidney maintains plasma bicarbonate concentration. Further, the kidneys maintain electrolyte
balance by excreting salt or by retaining salt depending on diet and environmental
condition.
Regulation of water electrolyte balance
The human body maintains a delicate balance of fluids and electrolytes to help ensure proper
functioning and homeostasis. When fluids or electrolytes become imbalanced, individuals are at
risk of organ system dysfunction. If an imbalance goes undetected and is left untreated, organ
systems cannot function properly and ultimately death will occur. Health practitioners must be
able to recognize subtle changes in fluid or electrolyte balances in their patients so they can
intervene promptly. Timely assessment and intervention prevent complications and save lives. The
body must carefully regulate intravascular fluid accumulation and excretion to prevent fluid
volume excesses or deficits and maintain adequate blood pressure. Water balance is regulated by
several mechanisms including ADH, thirst, and the Renin-Angiotensin-Aldosterone System
(RAAS).
Fluid intake is regulated by thirst. As fluid is lost and the sodium level increases in the intravascular
space, serum osmolality increases. Serum osmolality is a measure of the concentration of
dissolved solutes in the blood. Osmoreceptors in the hypothalamus sense increased serum
osmolarity levels and trigger the release of ADH (antidiuretic hormone) in the kidneys to retain
fluid. The osmoreceptors also produce the feeling of thirst to stimulate increased fluid intake.
However, individuals must be able to mentally and physically respond to thirst signals to increase
their oral intake. They must be alert, fluids must be accessible, and the person must be strong
enough to reach for fluids. When a person is unable to respond to thirst signals, dehydration occurs.
Older individuals are at increased risk of dehydration due to age-related impairment in thirst
perception. The average adult intake of fluids is about 2,500 mL per day from both food and drink.
An increased amount of fluids is needed if the patient has other medical conditions causing
excessive fluid loss, such as sweating, fever, vomiting, diarrhea, and bleeding.

The Renin-Angiotensin-Aldosterone System (RAAS) plays an important role in regulating fluid

output and blood pressure. When there is decreased blood pressure (which can be caused by fluid
loss), specialized kidney cells make and secrete renin into the bloodstream. Renin acts on
angiotensinogen released by the liver and converts it to angiotensin I, which is then converted to
angiotensin II. Angiotensin II does a few important things. First, angiotensin II causes
vasoconstriction to increase blood flow to vital organs. It also stimulates the adrenal cortex to
release aldosterone. Aldosterone is a steroid hormone that triggers increased sodium reabsorption
by the kidneys and subsequent increased serum osmolality in the bloodstream. Increased serum
osmolality causes osmosis to move fluid into the intravascular compartment to equalize solute
particles. The increased fluids in the intravascular compartment increase circulating blood volume
and help raise the person’s blood pressure.

Disorders of Water Balance

The body is in a state of fluid imbalance if there is an abnormality of total fluid volume, fluid
concentration, or fluid distribution among the compartments.
Fluid Deficiency
Fluid deficiency arises when output exceeds intake over a long period of time. There are two kinds
of deficiency, called volume depletion and dehydration, which differ in the relative loss of water
and electrolytes and the resulting osmolarity of the ECF. This is an important distinction that calls
for different strategies of fluid replacement therapy.
Volume depletion (hypovolemia) occurs when proportionate amounts of water and sodium are
lost without replacement. Total body water declines but osmolarity remains normal. Volume
depletion occurs in cases of hemorrhage, severe burns, and chronic vomiting or diarrhea. A less
common cause is aldosterone hyposecretion (Addison disease), which results in inadequate sodium
and water reabsorption.
Dehydration (negative water balance) occurs when the body eliminates significantly more water
than sodium, so the ECF osmolarity rises. The simplest cause of dehydration is a lack of drinking
water; for example, when stranded in a desert or at sea. It can be a serious problem for elderly and
bedridden people who depend on others to provide them with water, especially for those who
cannot express their need or whose caretakers are insensitive to it. Diabetes mellitus, ADH
hyposecretion (diabetes insipidus), profuse sweating, and overuse of diuretics are additional causes
of dehydration. Prolonged exposure to cold weather can dehydrate a person just as much as
exposure to hot weather.

Fluid Excess
Fluid excess is less common than fluid deficiency because the kidneys are highly effective at
compensating for excessive intake by excreting more urine. Renal failure and other causes,
however, can lead to excess fluid retention. Fluid excesses are of two types called volume excesses.
and hypotonic hydration. In volume excess, both sodium and water are retained and the ECF
remains isotonic. Volume excess can result from aldosterone hypersecretion or renal failure. In
hypotonic hydration (also called water intoxication or positive water balance), more water than
sodium is retained or ingested and the ECF becomes hypotonic. This can occur if you lose a large
amount of water and salt through urine and sweat and you replace it by drinking plain water.
Without a proportionate intake of electrolytes, water dilutes the ECF, makes it hypotonic, and
causes cellular swelling. ADH hypersecretion can cause hypotonic hydration by stimulating
excessive water retention as sodium continues to be excreted. Among the most serious effects of
either type of fluid excess are pulmonary and cerebral edema.
Electrolyte Imbalance.
Electrolytes are physiologically important for multiple reasons: They are chemically reactive and
participate in metabolism, they determine the electrical potential (charge difference) across cell
membranes, and they strongly affect the osmolarity of the body fluids and the body’s water content
and distribution. Electrolytes are salts such as sodium chloride, not just sodium or chloride ions.
In common usage, however, the individual ions are often referred to as electrolytes.

Table 2: Electrolyte Concentrations and the Terminology of Electrolyte Imbalances

Sodium Imbalance
The average Na + content of the human body is 60 mEqg, of which 50% is in extracellular fluid,
40% is in bone, and 10% is intracellular. The chief dietary source of sodium is salt added in
cooking. Excess sodium is largely excreted in the urine, although some is lost in perspiration.
Gastrointestinal losses are small except in diarrhea. Sodium balance is integrated with regulation
of extracellular fluid volume. Hyponatremia (sodium loss greater than water loss) may result from
inadequate Na + intake, excessive fluid loss from vomiting or diarrhea, diuretic abuse, and adrenal
insufficiency. Hyponatremia can decrease extracellular fluid volume, as occurs in congestive heart
failure, uncontrolled diabetes, cirrhosis, nephrosis, and inappropriate ADH
secretion. Hypernatremia results from loss of hypoosmotic fluid (e.g., in burns, fevers, high
environmental temperature, exercise, kidney disease, diabetes insipidus) or increased Na+ intake
(e.g., administration of hypertonic NaC1 solutions, ingestion of NaHCO3)

Potassium Imbalance
The average K + content of the human body is 40 mEq/kg. K+ occurs mainly in intracellular space.
+
It is required for carbohydrate metabolism, and increased cellular uptake of K occurs during
glucose catabolism. K+ is widely distributed in plant and animal foods, the human requirement
being about 4 g/day. Insulin and catecholamines promote a shift of K+ into the cells. Excess K+ is
excreted in the urine, a process regulated by aldosterone. Plasma K+ plays a role in the irritability
of excitable tissue. A high concentration of plasma K+ leads to electrocardiographic (ECG)
abnormalities and possibly to cardiac arrhythmia, which may be due to lowering of the membrane
potential. Low concentration of plasma K+ increases the membrane potential, decreases irritability,
and produces other ECG abnormalities and muscle paralysis. Hyperkalemia may occur in renal
disease and adrenal insufficiency owing to impairment of normal secretory mechanisms.
Hypokalemia may occur from loss of gastrointestinal secretions (which contain significant
amounts of K+) and from excessive loss in the urine because of increased aldosterone secretion or
diuretic therapy. Hypokalemia rarely results from a dietary deficiency, because most diets contain
ample amounts of potassium; it can occur, however, in people with depressed appetites.
Hypokalemia more often results from heavy sweating, chronic vomiting or diarrhea, excessive use
of laxatives, aldosterone hypersecretion, or alkalosis. As ECF potassium concentration falls, more
K+ moves from the ICF to the ECF. With the loss of these cations from the cytoplasm, cells
become hyperpolarized and nerve and muscle cells are less excitable. This is reflected in muscle
weakness, loss of muscle tone, depressed reflexes, and irregular electrical activity of the heart.

Chloride Imbalance
Hyperchloremia (>105 mEq/L) is usually the result of dietary excess or administration of
intravenous saline. Hypochloremia (< 95 mEq/L) is usually a side effect of hyponatremia but
sometimes results from hypokalemia. In the latter case, the kidneys retain K+ by excreting more
Na+, and Na+ takes Cl- with it. The primary effects of chloride imbalances are disturbances in acid-
base balance, but this works both ways—a pH imbalance arising from some other cause can also
produce a chloride imbalance.

Calcium Imbalance
Hypercalcemia (> 5.8 mEq/L) can result from alkalosis, hyperparathyroidism, or hypothyroidism.
It reduces the Na+ permeability of plasma membranes and inhibits the depolarization of nerve and
muscle cells. At concentrations greater or equal to12 mEq/dL, hypercalcemia causes muscular
weakness, depressed reflexes, and cardiac arrhythmia.
Hypocalcemia (<4.5 mEq/L) can result from vitamin D deficiency, diarrhea, pregnancy, lactation,
acidosis, hypoparathyroidism, or hyperthyroidism. It increases the Na+ permeability of plasma
membranes causing the nervous and muscular systems to be overly excitable

Phosphate Imbalance
Phosphate homeostasis is not as critical as that of other electrolytes. The body can tolerate broad
variations several times above or below normal concentration with little immediate effect on
physiology.