Al - Iraqia University/ College of Medicine

Al - Iraqia university Prof. Dr. Samia –Alshahwani College of medicine Y1 L7 . 12. 2015 Human Biology/ Molecules of life (Lipids, proteins & nucleic acids)  2.5 Lipids Objectives: -Compare the structure of fats, phospholipids, & steroids. -State the function of each lipid class. Lipids are, diverse in structure & function, do not dissolve in water because of absence of polar group, contain little oxygen & consist of carbon & hydrogen atoms, contain more energy per gram than other molecules; therefore, fats & oils function as energy-storage. Others (phospholipids) form cell membrane. Steroids are large class of lipids that includes sex hormones.

Fats & Oils: Fat, is animal origin (e.g. butter), solid at room temperature. Oil, of plant origin (e.g., corn oil & soybean oil), are liquid at room temperature. Fat uses:  Long-term energy storage.  Insulates against heat loss.  Forms protective cushion around organs. Steroids: Smaller lipid molecules function as chemical messengers. Emulsifiers: cause fats to mix with water. They contain molecules with non polar & polar ends. The molecules position themselves about oil droplet so that their polar ends project outward. The droplet disperses in water, means emulsification occurred. Prior to digestion of fatty foods, fats are emulsified by bile. Liver manufactures bile & gallbladder store it. Fats & oils formed when one glycerol molecule reacts with 3 fatty acid.(Fig. 2.16). A fat is called triglyceride, because it’s three-part structure, or term neutral fat, because the molecule is non polar & carries no charges. Waxes are molecules made of one fatty acid combined with another single organic molecule, usually alcohol. Wax prevents loss of moisture. cerumen or ear wax is thick wax produced by glands lining outer ear channel, it protects ear canal from irritation & infection by trapping particles, bacteria & viruses when ear wax is washed by swimming the result is painful swimmer ear.

Fig. 2.16 Structure of a triglyceride. Triglycerides formed when 3 fatty acids combine with glycerol by dehydration synthesis reactions. Reverse reaction starts digestion of fat; hydrolysis introduces water, & fatty acid–glycerol bonds are broken.

Saturated, Unsaturated, & Trans-Fatty Acids: A fatty acid is carbon–hydrogen chain ends with acidic group —COOH (Fig. 2.16, left). Most of fatty acids contain 16 or 18 carbon atoms per molecule, smaller with fewer carbons known. Fatty acids are saturated or unsaturated. Saturated fatty acids have no double bonds between carbon atoms. The chain is saturated, so to speak, with all the hydrogen it can hold. Unsaturated fatty acids have double bonds in carbon chain wherever number of hydrogen less than two per carbon Fig2.17.Oils, present in cooking oils, are liquids at 1 room temperature because of double bond creates bend in fatty acid chain. Such kinks prevent close packing between hydrocarbon chains & account for oils fluidity; saturated fats have no double bonds between carbons in fatty acid. Unsaturated fats have one or more double bond. mmmmore double bonds in fatty acid.

Fig. 2.17 Comparison of saturated, unsaturated, & trans fats. For a fat to be trans, hydrogen need to be on opposite sides of carbon–carbon double bond, butter contains saturated fatty acids & no double bonds, solid at room temp. Saturated fats, contribute to disease atherosclerosis. Atherosclerosis caused by formation of lesions, or atherosclerotic plaques, inside blood vessels. The plaques narrow blood vessel diameter, choking off blood & oxygen supply to tissues. Atherosclerosis is a cause of cardiovascular disease (heart attack & stroke). More harmful than naturally occurring saturated fats are trans fats (Fig. 2.17), created artificially using vegetable oils. Trans fats may be partially hydrogenated to make them semisolid. Complete hydrogenation of oils causes all double bonds to become saturated. Partial hydrogenation does not saturate all bonds. It reconfigures some double bonds, but some of hydrogen atoms end up on different sides of the chain. Trans fats are found in shortenings & solid margarines. in processed foods (snack foods, baked goods, & fried foods). Dietary guidelines from American Heart Association (AHA) advise replacing trans fats with unsaturated oils. In particular, monounsaturated oils (like olive oil, with one double bond in carbon chain). Polyunsaturated oils (many double bonds in the carbon chain) as corn oil, canola oil, & sunflower oil also fit AHA guidelines. Dietary Fat:For health, the diet should include some fat. The total recommended fat in a 2,000-calorie diet is 65 grams The Omega-3 Fatty Acids: (n-3 fatty acids).Some fat is essential to health, omega-3 fatty acids, Three- lanoline acid (ALA), docosahexaenoic acid (DHA), & eicosapenaenc acid (EPA). Omega-3 fatty acids are major component of fatty acids in the brain adequate amounts of them are important for children & adults. It offers protection against cardiovascular disease, DHA reduce risk of Alzheimer disease. DHA & EPA manufactured from APA in small amounts within our bodies, best sources of omega-3 fatty acids salmon & sardines. Flax oil, called linseed oil, is excellent plant-based source of omega-3 fatty acids, not overdo diet with excessive supplements as omega- 3s may cause health issues when taken in large doses.

Phospholipids: Have phosphate group (Fig. 2.19), constructed like fats, & except that in place of third fatty acid, there is phosphate group contains both phosphate & nitrogen. These molecules are not electrically neutral, as are fats, because phosphate & nitrogen- containing groups are ionized. They form polar (hydrophilic) head of molecule, & the rest becomes nonpolar (hydrophobic) tails. Phospholipids are primary components of cellular membranes. They spontaneously form a bilayer (a sort of molecular “sandwich”) in which the hydrophilic heads (sandwich “bread”) face outward toward watery solutions, & tails ( sandwich “filling”) form hydrophobic interior 2 Steroids: Are lipids that have different structure from fats. Have a backbone of 4 fused carbon rings. Each one differs by the attached molecules, called functional groups. Cholesterol is a component animal cell’s plasma membrane & is the precursor of several other steroids, such as sex hormones estrogen & testosterone. The liver makes all cholesterol the body needs.

Figure 2.19 Structure of a phospholipid. a- Phospholipids are structured like fats with one fatty acid is replaced by a polar phosphate group. Therefore, the head is polar, whereas the tails are nonpolar. b- This causes the molecules to arrange themselves in a “sandwich” arrangement when exposed to water— polar phosphate groups on the outside of the layer, nonpolar lipid tails on the inside of the layer. Dietary sources should be restricted because elevated levels of cholesterol, saturated fats, & trans fats are linked to atherosclerosis, Male sex hormone, testosterone, is formed in testes; female sex hormone, estrogen, is formed in ovaries, they differ by functional groups attached to same carbon backbone. Good and Bad Cholesterol Blood tests to analyze lipid profile are part of annual medical exams, total cholesterol need to be below 200, threshold of a healthy diet, LDLreferred to as “bad” cholesterol, and HDL is “good” cholesterol, these are not forms of cholesterol; are types of proteins. The lipoproteins in the body serve as a form of fat & cholesterol carrier, moving these nutrients around as needed.LDL is lipoprotein that is full of triglycerides & cholesterol, HDL is basically empty. Thus, a high LDL value indicates that carriers were usually full, meaning that diet must be providing too many of these nutrients. Other factors, as amount of dietary fiber, daily exercise, & genetics, play a role in regulating “good” & “bad” levels of these lipoproteins. Concentrations in mg/dL).

2.6 Proteins; Important in cell structure & function. functions are: Support: Structural proteins. Keratin, in hair & nails. Collagen support ligaments, tendons, & skin. Enzymes: Enzymes bring reactants together & thereby speed chemical reactions. They are specific for one type of reaction & only function at body temperature. Transport: Channel & carrier proteins in plasma membrane allow substances to enter & exit cells. Other proteins transport molecules in blood. hemoglobin in red blood cells is a complex protein that transports oxygen. Defense: Antibodies are proteins, combine with foreign substances, antigens prevent it from destroying cells & upsetting homeostasis. Hormones: Regulatory proteins, serve as intercellular messengers that influence metabolism. Insulin regulates the content of glucose in blood & in cells. Growth hormone determines individual height. Motion: The contractile proteins actin & myosin allow parts of cells to move & cause muscles to contract. Muscle contraction facilitates movement from place to place.

3 Amino Acids: Proteins are macromolecules with amino acid subunits. The central carbon atom in an amino acid bonds to a hydrogen atom and 3 other groups of atoms. named amino acid because one of these groups is an —NH2 (amino group) and another is a —COOH (carboxyl group, an acid). The third group is the R group for amino acid:

Fig. 2.21 The structure of some amino acids. Amino acids have amine group (H3N+), acid group (COO−), & R group, attached to central carbon atom. R groups (screened in blue) are different. Some R groups are nonpolar & hydrophobic; others are polar & hydrophilic. Still others are polar & ionized.

Amino acids differ according to their R group. R groups range from a single hydrogen atom to a complicated ring compound. Some R groups are polar & some are not. Also, amino acid cysteine ends with an —SH group, which often serves to connect one chain of amino acids to another by a disulfide bond, —S—S—. Several amino acids commonly found in cells are shown Fig.2.21. Peptides : Two amino acids join by a dehydration reaction between carboxyl group of one & amino group of another. Covalent bond between two amino acids is called a peptide bond. When three or more amino acids linked by peptide bonds, polypeptide result. The atoms associated with peptide bond share electrons unevenly because oxygen attracts electrons more than nitrogen. Therefore, hydrogen attached to nitrogen has a slightly (δ+), whereas oxygen has a slightly (δ−)

Proteins shape: Proteins cannot function unless they have a specific shape. When proteins are exposed to extreme heat & pH, they undergo irreversible change in shape called denaturation, e.g., addition of vinegar (an acid) to milk causes curdling, heating causes coagulation of egg whites, which contain a protein called albumin. Denaturation occurs because the normal bonding between R groups has been disturbed. Once a protein loses its normal shape, it is no longer able to perform its usual function. Change in protein shape is responsible for both Alzheimer disease and Creutzfeldt–Jakob disease (the human form of mad cow disease).

4 Levels of Protein Organization: Protein structure has at least 3 or 4 levels (Fig. 2.23). The first level, primary structure, is linear sequence of amino acids joined by peptide bonds. Each polypeptide has its own sequence of amino acids. The secondary structure comes when polypeptide takes on a certain orientation in space. Once amino acids are assembled into a polypeptide, the resulting C=O section between amino acids in the chain is polar, having a partially negative charge. Hydrogen bonding is possible between the C=O of one amino acid & N—H of another amino acid in a polypeptide. chain coiling results in α (alpha) helix, or a right-handed spiral & folding of chain results in a pleated sheet. Hydrogen bonding between peptide bonds holds the shape in place. The tertiary structure of a protein is its final, three dimensional shapes. In enzymes, polypeptide bends & twists in different ways. hydrophobic portions are packed on inside & hydrophilic portions on outside make contact with water. Tertiary structure of enzymes determines what types of molecules with which they will interact. The tertiary shape of polypeptide maintained by various types of bonding between R groups; covalent, ionic, & hydrogen bonding all occur.

Fig. 2.23 Levels of protein structure. structure of proteins differ significantly. Primary structure, sequence of amino acids, determines secondary & tertiary structure. Quaternary structure is created by assembling smaller proteins into a large structure. Some proteins have one polypeptide, others have more than one, each with its own primary, secondary, and tertiary structures. These separate polypeptides are arranged to give proteins a fourth level of structure, termed the quaternary structure. Hemoglobin is a complex protein having a quaternary structure; many enzymes also have quaternary structure. Each of 4 polypeptides in hemoglobin is associated 5 with a nonprotein heme group. heme group contains iron (Fe) atom that binds to oxygen; in that way, hemoglobin transports O2 to tissues. 2.7.Nucleic Acids. 2 types DNA (deoxyribonucleic acid) & RNA (ribonucleic acid) (Fig. 2.24), called nucleic acids because first detected in nucleus. DNA structure discovery has influence on biology. DNA stores genetic information in cell & organism. DNA replicates & transmit information when each cell & each organism—reproduces. Researchers are beginning to understand how genes function & are working on ways to manipulate them. Biotechnology is devoted to altering genes. Function of DNA & RNA: DNA molecule contains many genes, & genes specify sequence of amino acids in proteins. RNA is intermediary that conveys DNA’s instructions regarding amino acid sequence in a protein. If DNA’s information is faulty, illness results. Relation between a gene, a protein, & illness illustrated by sickle-cell disease, red blood cells are sickle-shaped it occur because in hemoglobin molecule, amino acid valine substitutes for an amino acid glutamine

Fig.2.24 The structure of DNA & RNA. a- In DNA, adenine & thymine are a complementary base pair. hydrogen bonds join them (like the “steps” in a spiral staircase). Likewise, guanine and cytosine pair. b- RNA has uracil instead of thymine, so complementary base pairing isn’t possible Exchanging one amino acid for another—a seemingly small change—makes red blood cells lose their normal round, flexible shape & become weak & easily torn. Effects on health result,when abnormal red blood cells go through small blood vessels, they clog blood flow & break apart. Sickle-cell disease is another cause of anemia, & it results in pain & organ damage.

Structure of DNA and RNA: DNA & RNA are polymers of nucleotide, there are differences in types of subunits ,differences give DNA & RNA unique functions. Nucleotide Structure : Complex of 3 types of subunit molecules—phosphate (phosphoric acid), a pentose (5-carbon) sugar, & nitrogen-containing base:

6 Nucleotides in DNA contain sugar deoxyribose, & nucleotides in RNA contain sugar ribose; this difference accounts for their respective names (Table 2.1). There are 4 types of bases in DNA: adenine (A), thymine (T), guanine (G), and cytosine (C)

The base can have 2 rings (adenine or guanine) or one ring (thymine or cytosine). In RNA, the base uracil (U) replaces base thymine. These structures are called bases because their presence raises the pH of a solution. Polynucleotide Structure: Nucleotides link to make a polynucleotide, called a strand, which has a backbone made up of phosphate–sugar–phosphate–sugar. The bases project to one side of the backbone. The nucleotides of a gene occur in a definite order, & so do the bases. Sequence of bases in DNA is known, human genome. Leading to improved genetic counseling, gene therapy, & medicines to treat causes of many illnesses. DNA is double-stranded, with two strands twisted about each other in form of double helix Fig. 2.24a. In DNA, two strands are held together by hydrogen bonds between bases. When coiled, DNA resembles a spiral staircase. When unwound, resembles stepladder. The uprights (sides) of the ladder are made of phosphate & sugar molecules, & the rungs of the ladder are made only of complementary paired bases. Thymine (T ) pairs with adenine (A), & guanine (G) pairs with cytosine (C). Complementary bases have shapes that fit together. Complementary base pairing allows DNA to replicate in a way that ensures that the sequence of bases will remain the same. This is important because it is the sequence of bases that determines the sequence of amino acids in a protein. RNA is single-stranded. When RNA forms, complementary base pairing with one DNA strand passes the correct sequence of bases to RNA (Fig. 2.24b). RNA is nucleic acid directly involved in protein synthesis. ATP: An Energy Carrier: In addition to being subunits of nucleic acids, nucleotides have metabolic functions. When adenosine (adenine plus ribose) is modified by the addition of three phosphate groups instead of one, it becomes ATP (adenosine triphosphate), which is an energy carrier in cells. ATP Structure Suits Its Function: ATP is high-energy molecule because the last two phosphate bonds are unstable & easily broken. Last phosphate bond is hydrolyzed, leaving molecule ADP (adenosine diphosphate) & & a molecule of inorganic

Fig. 2.25 ATP is the universal energy currency of cells. (Called a riphosphate). When cells need energy, ATP is hydrolyzed forming ADP & P . Energy released. To recycle ATP, energy from food is required & reverse reaction occurs: ADP & P join to form ATP, & water is given off

7 phosphate P (Fig. 2.25). energy released by TP breakdown used to synthesize macromolecules, as carbohydrates & proteins. In muscle, energy used for muscle contraction; & in nerve cells, used for conduction of nerve impulses. After ATP breaks down, it recycled by adding P to ADP. Fig. 2.25 input of energy is required to re- form ATP. Glucose Breakdown Leads to ATP Buildup; Glucose contains energy used as direct energy source in cellular reactions. Instead, energy of glucose is converted to that of ATP molecules. ATP contains an amount of energy that makes it usable to supply energy for chemical reactions. Muscles use ATP energy & produce heat when they contract. This is the heat that warms the body. Insufficient oxygen limits glucose breakdown and limits ATP buildup. Summary The 4 categories of organic molecules, examples, monomers &functions, are shown below:

Monomer molecule; Bind chemically to other molecule to form a polymer.

Polymer; Macro (large) molecule composed of many repeated subunits.

Thank you Samia 2015