Premed 1: General Chemistry PDF

Premed 1: General Chemistry CMHS,UAE University H2O Haider Raza-Biochemistry Water Water distribution in human body • ~60% of body wt. (~40L/70Kg man) • (men, 55-70% and women and obese 45-60%) Give me a reason???? • >50% intracellular (ICF=intracellular fluid); ~ 25L • ~ 15-20% extracellular...

Premed 1: General Chemistry CMHS,UAE University H2O Haider Raza-Biochemistry Water Water distribution in human body • ~60% of body wt. (~40L/70Kg man) • (men, 55-70% and women and obese 45-60%) Give me a reason???? • >50% intracellular (ICF=intracellular fluid); ~ 25L • ~ 15-20% extracellular (ECF) ~15L = interstitial (80% = 10L) + plasma (20% = 5L) • Na+, K+, Cl-, HCO3- and proteins (serum albumin) regulate water distribution and exchange in tissues and blood • The distribution of water is regulated by some key hormones and proteins. • Diseases (fever, diabetes, fasting, high blood pressure, dehydration, organ failure) may affect the distribution of water. Physiological Functions of Water 1. 2. 3. 4. 5. 6. 7. Dissolves biological molecules such as electrolytes, sugars, amino acids, enzymes and hormones Helps in diffusion, transport and storage of fats, carbohydrates, drugs, nutrients and metabolites Maintains the three dimensional structures of biomoleculesproteins, DNA, RNA, complex sugars Maintains pH, temperature and osmotic pressure Organizes cellular membranes-lipid bilayers, receptors. Maintains blood pressure and tissue integrity- kidney functions and solute distribution (water retention will raise BP) Lubricates body joints by making jelly like slippery fluid with complex protein-carbohydrates (proteoglycans/glycosaminoglycans) Three Important properties of water make it most important biological solvent: 1. 2. 3. Polarity: determines solubility, hydrophilcitydistribution of nutrients, electrolytes, fluids and drugs Hydrogen bonding: hydrophobicity, membrane structures in cells, micelles formation and transport of lipids,structures of protein, DNA and biomolecules Ionization: regulate body pH (pH 7.4), acid-basebuffers ,enzyme actions, drug absorption and storage Water is a polar molecule Water surrounds the charged (polar-hydrophilic) molecules and make them soluble NaCl Hydrophilic molecules: Charged (polar) groups-Water soluble • Charged or ionized molecules are water soluble-Hydrophilic e.g. glucose, amino acids, vitamin B complexes • Positively charged ions (Na+) or molecules are attracted towards the negatively charged oxygen in water. (water retention-high BP) • Negatively charged ions (Cl-) are attracted towards the positively charged hydrogen in water. • Thus water is responsible for distribution of electrolytes and other water soluble materials in the blood and tissues. • Excess common salt (Na+ Cl- ) intake will increase water retention in the body and increases blood pressure. • Electrolytes and water distribution is further controlled by some hormones. • Clinical relevance: High blood pressure/ diabetes/cardiovascular diseases Hydrophobic Attractions Between non-polar groups (water insoluble): lipids in water Hydrophobic attraction • Uncharged or nonpolar molecules are repulsed away from water as they do not have any attraction towards waterHydrophobic-insoluble • Because of an organized hydrogen boding in water molecules, they push away the nonpolar groups so that they aggregate to each other away from water. Different proteins acquire different structures due to their water solubility, H-bonding and hydrophobicity Arrangements of polar and nonpolar groups in micelles and membranes • The surface of the micelles (vesicles) mainly contain water soluble and amphipathic (both hydrophilic and hydrophobic) more polar lipids like, fatty acids, phospholipids and free cholesterol • The center core of the micelles contain more hydrophobic lipids like esterified cholesterol and triglycerides • On the membrane surface polar groups (hydrophilic) are facing out side and non-polar groups are buried between the lipid bilayer • Proteins and other molecules (e.g. sugars, proteins etc) are also arranged according to their hydrophilicity and hydrophobicity Micelles and bilayer In membranes Arrangement of fatty acids (palmitic acid): polar and non polar groups A stable micelles (lipoprotein particles-vesicles) increase the water solubility of lipids, cholesterol and drugs (facilitates their transport) Hydrophilic proteins, phospholipids,cholesterol etc Hydrophobic lipids Phospholipids, proteins and bile salts (digestive system) are good emulsifying agent • The lipid digestion by enzymes (e.g. Green balls in figure) are best explained by the arrangement of polar groups (bile salts, proteins and phospholipids) on the surface and nonpolar groups in the center core of lipid micelles- to make a connection between lipid digesting enzymes and dietary lipids during digestion-Emulsification. Bile salts and phospholipids lipids enzyme Transport of cholesterol and lipid soluble compounds in Blood: Lipoprotein particles (like micelles) • When molecules have both polar and nonpolar groups (amphipathic) they arrange themselves in such a way that the polar groups are phasing outside and nonpolar groups in the core in round vesicles of lipoprotein particles. • That is how complex insoluble lipids, drugs and cholesterol are transported in blood as lipoprotein particles- disease risk • Cell membrane formation is another example,where phospholipids, cholesterol and proteins are arranged in a bilayer fashion according to their water solubility. Body water distribution and Clinical relevance: Water Intake ~ 2-2.5L /day: Ingestion of water (food and drinks) is regulated by hormone. Metabolic water by food oxidation (<0.5L) Output ~2-2.5L:Urine, skin, lungs, faeces Distribution: Regulated by electrolytes (Na+, K+,Cl-) and serum proteins (mainly serum albumin); Regulating hormones- aldosterone, vasopressin and angiotensin II. Increased sodium chloride (common salt) will increase water retention (riskhypertension). Edema: accumulation of water in the tissues as seen in high blood pressure and in serum protein (albumin) deficiency. Dehydration: Loss of water from the tissues as seen in diabetes (excess urination) and diarrhea. High BP: Excess of water retention Low BP: Water loss/dehydration Study questions 1. Explain the arrangements of hydrophobic lipids and amphipathic lipids in a lipoprotein particles as well as in the membrane bilayers 2. Explain the role of serum albumin in retaining water in the blood. 3. Lipoprotein particles: are surrounded by hydrophobic lipids contains center core made of hydrophilic lipids are rich in hydrophobic cholesterol esters in the core nonpolar triglycerides are arranged on the surface 4. Explain the mechanism of transport of cholesterol in the blood. 5. Explain why high sodium chloride (salt) intake may increase the risk for high blood pressure