Biochemistry: An Overview PDF

1. Biochemistry Power to Understand What We Are!  What is Biochemistry? Generally biochemistry is the study of life at the molecular level. Uses basic laws of chemistry, biology and physics to explain processes of living cells. Because life depends on biochemical reactions, bioc...

1. Biochemistry Power to Understand What We Are!  What is Biochemistry? Generally biochemistry is the study of life at the molecular level. Uses basic laws of chemistry, biology and physics to explain processes of living cells. Because life depends on biochemical reactions, biochemistry has become the basic language of all life sciences.  Why study biochemistry?  Lead us to fundamental understanding of life.  Understand important issues in medicine, health, and nutrition.  Has led to greater molecular understanding of diseases such as diabetes, sickle cell anemia, and cystic fibrosis.  Next frontier: AIDS, cancer, Alzheimer’s Disease.  Advance biotechnology industries  Biotechnology is the application of biological cells, cell components, and biological properties to technically and industrially useful operations. i. Major objective of biochemistry  Complete understanding at the molecular level of all the chemical processes associated with living cells. Isolate-the numerous molecules found in cells, Determine-their structures, Analyze-how they function. ii. Further objective  Attempt to understand how life began.  An appreciation of the biochemistry of less complex form of life is often direct relevance to human biochemistry.  1.2 The major chemical constituents iochemistry of cells = the chemistry of life Elements - These are single substances which cannot be broken down any more. there are 110 different elements that are known to man.  …cont’d The living matter is composed of mainly six elements-Carbon, Hydrogen, Oxygen, Nitrogen, Phosphorus and Sulphur. (CHONPS) These elements together constitute about 90% of the dry weight of the human body. Several other functionally important elements are also found in the cells.  These include Ca, K, Na, Cl, Mg, Fe, Cu, Co, Zn, F, Mo and Se. Carbon-a unique element of life Carbon is the most predominant and versatile element of life. It possesses as unique property to form infinite number of compounds. This is attributed to the ability of carbon to form: stable covalent bonds and C-C chains of unlimited length.  Carbon can form immensely diverse compounds, from simple to complex. Compounds - These are two or more elements combined. These elements are bonded Complex Molecule together. Simple Molecule Methane with 1 Carbon DNA with tens of atom Billions of Carbon  Organization of Life  Life is composed of lifeless chemical molecules. elements simple organic compounds (monomers) macromolecules (polymers) supramolecular structures organelles cells tissues organisms  Complex Biomolecules  As regards lipids, it may be noted that they are not biopolymers in a strict sense, but majority of them contain fatty acids.  Composition of the body and major classes of molecules The human body is composed of a few elements that combine to form a great variety of biomolecules. Biomolecules are compounds of carbon with a variety of functional groups Element The simplest kind of matter which can not be split in to two or more simpler substances by chemical reactions. Chemical composition of a normal man (weight 65 kg) Constituent Percent (%) Weight (k g) Water 61.6 40 Protein 17.0 11 Lipid 13.8 9 Carbohydrate 1.5 1 Minerals 6.1 4 g. Some common functional groups of biomolecules. 1.3 Acid, Base and Buffer systems 14 5 coffee 15  The Body and pH Homeostasis of pH is tightly controlled Extracellular fluid = 7.4 Blood = 7.35 – 7.45  If pH is < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45 16  …cont’d  Acids are H+ donors.  Bases are H+ acceptors.  Acids and bases can be: Strong – dissociate completely in solution HCl, NaOH Weak – dissociate only partially in solution Lactic acid, carbonic acid A weak acid has a characteristic dissociation constant, Ka.  The relationship between the pH of a solution, the Ka of an acid, and the extent of its dissociation are given by 17 the Henderson-Hasselbalch equation.  Acid/conjugate base pairs HA + H2O A- + H3O+ HA A - + H+ HA = acid ( donates H+)(Bronstad Acid) A- = Conjugate base (accepts H+)(Bronstad Base) Ka = [H+][A-] Ka & pKa value describe tendency to loose H+ [HA] pKa = - log Ka large Ka = stronger acid small Ka = weaker acid  …cont’d A buffer is a mixture of an undissociated acid and its conjugate base (the form of the acid having lost its proton). It causes a solution to resist changes in pH when either H+ or OH- is added. A buffer has its greatest buffering capacity in the pH range near its pKa (the negative log of its Ka).  Henderson-Hasselbalch Equation HA = weak acid 1) Ka = [H ][A ] + - [HA] A- = Conjugate base 2) [H+] = Ka [HA] [A-] 3) -log[H+] = -log Ka -log [HA] * H-H equation describes [A-] the relationship between pH, pKa and buffer 4) -log[H+] = -log Ka +log [A-] concentration [HA] 5) pH = pKa +log [A-] [HA]  … cont’d If the pKa for a weak acid is known, this equation can be used to calculate the ratio of the unprotonated to the protonated form at any pH. From this equation, you can see that a weak acid is 50% dissociated at a pH equal to its pKa. Most of the metabolic carboxylic acids have pKa ‘s between 2 and 5, depending on the other groups on the molecule.  The pKa reflects the strength of an acid.  The body produces more acids than bases Acids take in with foods. Cellular metabolism produces CO2. Acids produced by metabolism of lipids and proteins. CO 2 Volatile acid H2CO3 CO2+ H2O CO2 CO2 H2SO4 H3PO4 Fixed acid Uric acid Lactic acid Ketone body 22  Maintenance of blood pH Three lines of defense to regulate the body’s acid-base balance – Blood buffers – Respiratory mechanism – Renal mechanism 23  Buffer systems Take up H+ or release H+ as conditions change Buffer pairs – weak acid and a base Exchange a strong acid or base for a weak one Results in a much smaller pH change 24  Principal buffers in blood in Plasma in RBC H2CO3 / HCO3- 35% 18% HHb / Hb- 35% HPro / Pro- 7% H2PO4- / HPO42- 5% Total 42% 58% 25  Bicarbonate buffer Predominant buffer system in ECF Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) HCO3- : H2CO3: Maintain a 20:1 ratio [HCO3 － ] pH=pKa+lg H2CO3 H+ + HCO3- [H2CO3] 24 = 6.1+ lg 1.2 20 = 6.1+ lg 1 26 = 6.1+1.3 = 7.4  Bicarbonate buffer HCl + NaHCO3 ↔ H2CO3 + NaCl NaOH + H2CO3 ↔ NaHCO3 + H2O 27  Phosphate buffer Major intracellular buffer NaH2PO4-Na2HPO4 H+ + HPO42- ↔ H2PO4- OH- + H2PO4- ↔ H2O + HPO42- 28  Protein Buffers Include plasma proteins and hemoglobin Carboxyl group gives up H+ Amino Group accepts H+ 29  2. Respiratory mechanisms CO2 CO2 Exhalation of CO2 Rapid, powerful, but only works with volatile acids H+ + HCO3- ↔ H2CO3 ↔ CO2 + H20 Doesn’t affect fixed acids like lactic acid Body pH can be adjusted by changing rate and depth of breathing 30  3. Kidney excretion Most effective regulator of pH The pH of urine is normally acidic (~6.0) – H+ ions generated in the body are eliminated by acidified urine. Can eliminate large amounts of acid (→H+) Reabsorption of bicarbonate (HCO3-) (←HCO3-) Excretion of ammonium ions(NH4+) (→NH4+) If kidneys fail, pH balance fails 31  Rates of correction Buffers function: almost instantaneously Respiratory mechanisms: take several minutes to hours Renal mechanisms: may take several hours to days 32 33  Acid-Base Imbalances pH< 7.35: acidosis pH > 7.45: alkalosis The body response to acid-base imbalance is called compensation – The body gears up its homeostatic mechanism and makes every attempt to restore the pH to normal level. – May be complete if brought back within normal limits – Partial compensation if range is still outside norms. 34  Acid-Base Imbalances Acidosis- a decline in blood pH ↓ – Metabolic acidosis: due to a decrease in bicarbonate. ↓ – Respiratory acidosis: due to an increase in carbonic acid. ↑ Alkalosis- a rise in blood pH ↑ – Metabolic alkalosis: due to an increase in bicarbonate.↑ – Respiratory alkalosis : due to a decrease in carbonic acid. ↓ 35  Compensation If underlying problem is metabolic, hyperventilation or hypoventilation can help: respiratory compensation. If problem is respiratory, renal mechanisms can bring about metabolic compensation. 37  Metabolic Acidosis Bicarbonate deficit (↓) - blood concentrations of bicarb drop below 22mEq/L (milliequivalents / liter) Causes: – Loss of bicarbonate through diarrhea or renal dysfunction – Accumulation of acids (lactic acid or ketones) – Failure of kidneys to excrete H+ Commonly seen in severe uncontrolled DM (ketoacidosis). 38  Respiratory Acidosis Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg. Hypercapnia – high levels of CO2 in blood Causes: – Depression of respiratory center in brain that controls breathing rate – drugs or head trauma – Paralysis of respiratory or chest muscles – Emphysema 40  Metabolic Alkalosis Bicarbonate excess↑ - concentration in blood is greater than 26 mEq/L Causes: – Excess vomiting = loss of stomach acid – Excessive use of alkaline drugs – Certain diuretics – Endocrine disorders: aldosterone ↑ – Heavy ingestion of antacids 42  Respiratory Alkalosis Carbonic acid deficit↓ pCO2 less than 35 mm Hg (hypocapnea) Most common acid-base imbalance Primary cause is hyperventilation – Hysteria, hypoxia, raised intracranial pressure, excessive artificial ventilation and the action of certain drugs (salicylate) that stimulate respiratory centre. 44  Mixed acid-base disorders Sometimes, the patient may have two or more acid-base disturbances occurring simultaneously. In such instances, both HCO3- and H2CO3 are altered. 46 Reading Assignment 1. Biological importance of Water 2. Types of chemical bond 47 ,