Biomolecules - continued III. The structure and function of proteins - Huge variety of roles, most versatile of the biomolecules. - Why? Consider 3 AA peptide = 20 X 20 X 20 = 203 = 8000 possible tripeptide sequences! 1) Protein Structure -Proteins are large macromolecules that consist of long chains of sub-units called Amino Acids -only 20 types of AAs are necessary for the human body -this number varies from species to species -for example, cats require the AA "taurine" for normal development, which is not required at all in humans - Human body can synthesize all but 9 of the 20 AAs - these 9 must come from diet and are called essential amino acids. -There are four basic parts to an Amino Acid 1) Center carbon (CH) 2) Amino Group (NH2) 3) Carboxyl (acid) Group (COOH) 4) Side Chain (R) -The side chain is usually referred to as the "R" group (remainder) -Each type of AA has a unique R group -R groups vary greatly in structure, from a simple H to a highly complex ring-structure -physical and chemical properties of the R group determine the unique characteristics of a particular AA - Peptide bond - when two AAs are joined by dehydration synthesis -two linked AAs are called a dipeptide -many AAs linked in this way are called a Polypeptide -all proteins are polypeptide chains -Proteins have complex structures besides this simple chain -the three dimensional structure of a protein is called its Conformation -the protein's conformation determines its function. -There are four levels of protein structure: 1) Primary structure -this is the AA sequence in the polypeptide chain -1' structure is genetically determined by DNA -each type of protein has a unique primary structure 2) Secondary structure -a spontaneous twisting or folding of the primary structure -caused by weak attractions between different parts of the primary structure as it is constructed -these weak interactions are mostly hydrogen bonds -within a given primary structure, there are attractions between H and O or N -these attractions cause twisting or folding of the 1' structure -common results include the alpha-helix (spiral staircase) or the Beta-pleated sheet (like a pleated skirt) -secondary structure is usually very regular in nature (ie repetitive) 3) Tertiary structure -Irregular contortions from bonding between R groups caused by: a) hydrophobic R groups that congregate toward the center b) strong bonds that form between R groups, such as disulfide bridges c) other weaker bonds 4) Quaternary structure -Conglomerates of more than one separate polypeptide chain that bond to form a larger functional protein - Each of these polypeptides are referred to as a subunit - some examples of molecules with quaternary structure include: a) Ribosomes (at least two subunits) b) Hemoglobin (four subunits 2alpha and 2beta) c) Collagen (three helicies twisted into another helix - like a rope) -Factors determining conformation 1) polypeptide chain spontaneously arranges itself into its 3-dimensional structure - occurs at the time of synthesis 2) proteins can be forced to unravel by changing the pH, salt concentration, or temperature of its environment -these changes interfere with the bonds (strong and weak) that produce the 3-D structure and cause the protein to denature or unravel -denatured proteins loose their biological functions -if the denatured protein remains dissolved in water, it may return to its conformation if the proper environment is restored -If the protein precipitates or reacts in some other way, it cannot reform. These observations have clear implications: the integrity of the primary structure is critical to the normal functioning of the protein -most errors in primary structure are harmful or lethal -situations where the effects of errors in 1º structure are sub-lethal -sickle cell -1 AA substitution in Hb causes a shift in conformation cascading to serious effects on individual health Protein Functions: Proteins serve many functions a) Structural proteins: building material -Collagen & Elastin: ligaments, cartilage, bone, tendons; Keratin: hair, nails b) Storage Proteins: AA storage -Ovalbumin: egg white, stores AAs for developing embryo -Casein: Milk protein: major source of AAs for baby mammals c) Transport Proteins: for moving other substances -Hemoglobin: for Oxygen transport by blood -Glycoproteins: transport across plasma membrane d) Hormonal Proteins: coordination of bodily functions -insulin: regulates blood sugar levels e) Receptor proteins: huge array of types, used to detect chemical signals -ACH receptor responsible for muscle contraction -Growth hormone receptors, etc. f) Contractile proteins: movement -actin and myosin: muscle contraction -responsible for movements of cilia and flagella g) Defensive proteins: antibodies which fight bact & viruses h) Enzymes: Critical catalysts for most chemical reactions in biological systems. Why do we need enzymes and how do they work? -Most chemical reactions proceed slowly at biological temperatures -without assistance, reaction rates are too slow to sustain life. -One way to speed up reaction rates is to add heat, but this approach has at least two problems 1) heat will destroy cells before a useful effect is obtained 2) Increased heat acts equally on all reactions simultaneously, - there's no control -living things deal with this problem by having specialized catalysts (enzymes) that speed up the rate of targeted reactions. -enzymes are specific to a single reaction due to the active site -concentration and activity of any single enzyme can be tightly controlled. -in synthesis, they function by binding the two substrates together in the correct configuration for a reaction to occur. -In break down, they bind to large substrates and break them apart -Large enzymes that have this function can often break down many substrates -Many venoms work in this way with multiple active sites. IV. The structure and function of Nucleic acids: 1) there are two types of nucleic acids: DNA and RNA -these molecules are necessary to synthesize proteins and to perpetuate life -DNA (Deoxyribonucleic acid) is unique among biological molecules because it provides directions for its own replication -DNA molecules are very long, contain thousands of Genes which are responsible for inheritance -DNA is organized in cell nuclei as chromatin or chromosomes -The structure of DNA provides the information for all cellular activities and that information must be transcribed in order to be translated into structures and molecules -RNA (Ribonucleic acid) is produced by DNA, specifically, mRNA (messenger RNA) conveys the information encoded on DNA to the protein making machinery in the cytoplasm (ribosomes) DNA>>>RNA>>>Protein 2) Both DNA and RNA are polymers of molecules called nucleotides which, as in other cases are chains formed from dehydration synthesis. 3) The structure of nucleotides: -each nucleotide has three parts: a) A Nitrogenous Base b) A pentose sugar (Deoxyribose in DNA, Ribose in RNA) c) a phosphate group. -There are two families of nitrogenous bases 1) Pyrimidines: single ring: thymine (T), cytosine (C), Uracil (U) -T and U are interchangable, but only T exists in DNA and only U exists in RNA 2) Purines: double ring: adenine (A) and guanine (G) -all of these compounds contain nitrogen and tend to increase the pH of a solution, hence the term "Nitrogenous Base" -Each type of Base (A, G, C, T, U) has a slightly different functional group and therefore slightly different chemical properties. -phosphates can connect to two sugars at once (by dehydration synthesis) -This results in a repetitive "backbone" of sugar-P-sugar-P-sugar- a Polynucleotide -this backbone has appendages: nitrogenous bases -the sequence of bases along the backbone is unique to each gene -Because genes are at least hundreds of bases long, the number of combinations is limitless -RNA is a single stranded molecule (one "backbone") -DNA is a double stranded molecule consisting of two backbones twisted around each other forming a Double helix (spiral staircase). -The two strands of DNA are held together by hydrogen bonds between purine and pyrimidine bases: this is called complementary base pairing -T always pairs with A -G always pairs with C -therefore, # of pyrimidines is always equal to # of purines -the exact sequence of bases specifies the exact sequence of amino acids in the primary structure of the protein. [code is triplet of bases for an amino acid] 4) There is one other important use of nucleotides in the cell. -ATP (adenosine triphosphate) is a very special type of nucleotide -ATP is composed of adenine bonded to ribose (=adenosine) -attached to adenosine are three phosphate groups -the bonds that attach the phosphate groups are "high energy" bonds -ATP is thus the energy currency of the cell -the energy available from ATP is used by the cell for a variety of functions including: synthesis, active transport, nervous conduction, and muscle contraction. -to keep a constant supply of ATP on hand, ADP or AMP must be re-phosphorylated -obviously, adding phosphates to depleted nucleotides costs energy -This energy is derived from aerobic cellular respiration (mostly from the breakdown of glucose) which occurs in both the cytoplasm and within the mitochondria.