1Section 2 Chemical and Biologic Foundations of BiochemistryChapt. 4. Basics of BiochemistryStudent 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 pHMaintenance of body pH is critical:• 13-22 mol/day of acid producedfrom normal metabolism• Buffers maintain neutral pH• CO2is expired through lungs• NH4+and ions are excreted through kidneysFig. 4.1WaterFig. 4.2 Fluid compartments in typical 70-kg manWater is solvent of life:• ~ 60% of body is water• bathes cells• transports compounds in blood• separates charged molecules• dissapates heat• participates in chemical reactionsHydrogen bonds in waterFig. 4.3Fig. 4.4: A. H bonds B. Hydration shells around ionsHydrogen bonds:• Dipolar nature makes H2O good solvent; unequal sharing of e-• H bonds are weak (5% of covalent)• Dynamic lattice; thermoregulation(Sweat cools)2ElectrolytesTable 4.1 Ions in Body FluidsECF mmol/L ICF mmol/LCationsNa+145 12K+4 150AnionsCl-105 5HCO3-25 12inorganic phosphate 2 100Energy-requiring transporter (Na+/K+ ATPase) maintains the Na+/K+ gradientOsmolality and water movementWater distributes between compartments• Acccording to osmolality (concentration of dissolved molecules mOsm/kg H2O)• Cell membrane semi-permeable• H2O moves from its high conc to its low (or from low solute -> high)Ex. Water from blood to urineto balance excretion of ionsEx. Hyperglycemia: high sugar in bloodpulls water from cellsII. Acids and basesFig. 4.5Review Acids and Bases:• Acids donate H+ (proton)• Bases (like OH-) accept H+pH = -log [H+]; acidic < pH 7; basic > pH 7in pure H2O, [H+] = 10-7mol/L = pH of 7Kd= [H+] [OH-]/ [H2O]; but [H2O] ~ constantKw= [H+] [OH-] = 1 x 10-14increase [H+] -> decrease [OH-], & vice versaTable 4 Acids in blood of personAcid anion pKa sourceSulfuric (H2SO4) SO42-completelydissociated dietary aaCarbonic acid (R-COOH) R-COO- 3.8 CO2from TCAAcetic acid (R-COOH) R-COO- 4.76 ethanol metabAcetoacetic acid(R-COOH) R-COO- 3.62 fatty acid oxidketone bodiesAmmonium ion(NH4+) NH39.25 diet N-containing3AcidsStrong acids dissociate completely;Weak acids dissociate partially – depends on pHFig. 4.6: HA <-> A-+ H+Acid ends in -ic, Conjugate baseends in -ateKetone bodies are weak acids Henderson-Hasselbalch equationKa, 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 10-5NH4+= 5.6 x 10-10Henderson-Hasselbalch equationHenderson-Hasselbalch equation describes relationship between pH of a solution, Kaof acid and extent of its dissociationpKa= negative log of KaFor 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 pKaof 5:much more is dissociated at any pHBuffers resist changes in pHFig. 4.7Buffers resist changes in pHwithin ~ 1 pH unit of pKaAcetic acid:pH = pKa= 4.76; 50% dissociated: [A]: [HA] = 1:1pH 3.76: [A-]: [HA] = 1:10(not much A- left to receive more H+)4Metabolic buffersBuffers maintain body pH in narrow ranges:despite huge amounts of acid produced/ dayBlood: pH 7.36-7.44Intracellular: pH 6.9-7.4Beating heart: pH 6.8-7.8Major acid is CO2from TCA cycleMetabolic buffers: Bicarbonate-carbonic acid (ECF)Hemoglobin (rbc), proteins (cells and plasma)Phosphate in all cell typesBicarbonate bufferFig. 4.8Bicarbonate is metabolic buffer; • Acid derived from CO2produced 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 blood = 6.1 + log[HCO3-]/ 0.03 PaCO2where HCO3-= mEq/ml; PaCO2partial pressure arterial blood (mm Hg)(much more later in Physiology)Biological buffers maintain pHBuffering 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 Fig. 4.9Urinary hydrogen, ammonium and phosphateNonvolatile 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• NH3is major buffer (NH3+ H+<-> NH4+)NH3 is toxic to neurons; NH4+ is generated in kidney5Homeostasis requires fluid balanceFluid balance is critical for homeostasis:Dehydration if salt and water intake < combined rates of renal and extrarenal lossEven if fasting, urinary water dilutes solutes and ions; expired air loses water.Hormones help monitor blood volumes, osmolarityKey conceptsKey concepts:• Water is the basis of life – 60% of body – H bonds• Intracellular and extracellular (interstitial, blood, lymph)• Compounds dissolved in water act as acids, bases• 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• CO2+ water -> carbonic acid -> bicarbonate and H+Clinical commentsDi Abetes: type I diabetes (IDDM) – autoimmune destruction of β-cells of pancreasketoacidosis from blood ketoacids, lowers pHrespiration increases to compensate somewhatincrease urine to dilute blood glucose; Hyperventilate can give alkalosis in normal person; Chapt 4. Review questionsChapter 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 basesb. buffers work best at pH at which they are completely dissociatedc. buffers work best at the pH at which they are 50% dissociatedd. buffers work best at one pH unit lower than the pKae. buffers work equally well at all concentrations.6Chapt. 5 Major compounds of the BodyChapt. 5 Structures of Major CompoundsStudent Learning Outcomes:• Describe structures, functions of major biological compounds:• Carbohydrates have C, H, O• Lipids have fatty acids