Enzymes and Diseases (Final Period) PDF

CHEM 131.1 Mr. Sio | Enzymes PROPERTIES OF ENZYMES Topic Outline: Enzymes 1. Enzymes are highly spe...

CHEM 131.1 Mr. Sio | Enzymes PROPERTIES OF ENZYMES Topic Outline: Enzymes 1. Enzymes are highly specific to a reaction Ribozyme (Lock-and-Key Model). Properties of Enzyme 2. They alter or speed up the rates of a chemical Distribution reaction. Specificity 3. They remain unchanged after reaction. Factors Affecting Enzyme Activity 4. Enzymes are affected by temperature and pH. Naming Enzymes 5. They catalyze reversible reactions. Key Terms CERTAIN TYPES OF MOLECULES/BONDS/REACTIONS LIMITED CONFINED TO Lock-and-Key Model & Induced-Fit Model Mechanisms of Enzyme ENZYME SPECIFICITY Enzymes in Medicine Enzyme specificity is the extent to which an enzyme’s PROTEIN CATALYST FOR activity is restricted to a specific substrate, a specific COMPOUND group of substrates, a specific type of chemical bond, or A BIOCHEMICAL REACTION ENZYME An enzyme is a compound, usually a protein, that acts a specific type of chemical reaction. The degree of as a catalyst for a bio- chemical reaction. Each cell in the enzyme specificity is determined by the active site. human body contains thousands of differ- ent enzymes Some active sites accommodate only one particular because almost every reaction in a cell requires its own compound, whereas others can accommodate a “family” specific enzyme. Enzymes cause cellular reactions to of closely related compounds. occur millions of times faster than corresponding uncatalyzed reactions. As catalysts, enzymes are not UREASE: Catalyzes the hydrolysis of urea only. consumed during the reaction but merely help the TRYPSIN: Catalyzes the hydrolysis of the peptide bonds reaction occur more rapidly. of protein molecules. LIPASE: Catalyzes the hydrolysis of any triacylglycerols Enzymes are proteins that increase the rate of reaction (TAG) but still does not affect carbohydrates or proteins. by lowering the activation, which is the minimum amount It is less-specific. enzyme converts substrate to products of energy required for the reaction to take place). They FACTORS AFFECTING ENZYME ACTIVITY speed up a chemical reaction, but are not changed by Enzyme activity is a measure of the rate at which an the reaction. enzyme converts substrate to prod- ucts in a biochemical reaction. Factors that affect enzyme activity Most enzymes are globular proteins. Some are simple include temperature, pH, substrate concentration, and proteins, consisting entirely of amino acid chains. Others enzyme concentration. are conjugated proteins, containing additional chemical HIGHER MOLECULES ARE MOVING FASTER components. TEMP - AND MORE FREQUENTLY SENSITIVE TO THEIR TEMPERATURE: ~ ENVIRONMENT Temperature is a Enzymes undergo all the reactions of proteins, including measure of the kinetic denaturation. Slight alterations in pH or temperature energy (energy of affect enzyme activity dramatically. motion) of molecules. At RIBOZYME higher temperatures A few enzymes are now known that are made of molecules are moving ribonucleic acids and that catalyze cellular reactions faster and colliding more involving nucleic acids. Ribozymes catalyze the frequently. This concept self-cleavage of certain proteins of their own molecules applies to collisions and have been implicated to generate peptide bonds. between substrate molecules and ENZYMEs -) catalyze cellular reaction > involving nucleic acid enzymes. As the tem- ribonucleic acid - the perature of an RIBOZYMES > - catalyze self-cleavage of certain proteins of their enzymatically catalyzed own molecule KB | 1 TEMPERATURE OF REACTION INCREASES SO DOES THE RATE (VELOCITY) - , - ENZYMATICALLY CATALYZED OF THE REACTION  reaction increases, so does the rate (velocity) of the concentration of substrate in a reaction is much higher reaction. than that of the enzyme. If the amount of substrate present is kept constant and the enzyme concentra- tion The temperature that produces maximum activity for an is increased, the reaction rate increases because more enzyme is known as the optimum temperature for that substrate molecules can be accommodated in a given enzyme. Optimum temperature is the temperature at amount of time. which an enzyme exhibits maximum activity. pH: Small changes in pH (less than one unit) can result in enzyme denaturation and subsequent loss of catalytic activity. Most enzymes exhibit maximum activity over a very narrow pH range. Only within this narrow enzymes functioan e pH range do the row pl range. enzyme’s amino acids exist in properly charged forms. Optimum pH is the pH at which an enzyme exhibits maximum activity. > enzymes - are used to their SUBSTRATE maximum extent CONCENTRATION: As substrate concen- tration increases, the point is eventually reached where enzyme capabilities are used to their maximum extent. Each substrate must occupy an enzyme active site for a finite amount of time, and the products must leave the site before the cycle can be repeated. When each enzyme molecule is working at full capacity, the incoming substrate molecules must “wait their turn” for an empty active site. ~ More enzyme = the Faster the reaction rate ENZYME CONCENTRATION: DISTRIBUTION Because enzymes are not consumed in the Enzymes are randomly distributed but are specifically reactions they catalyze, located in the cell. the cell usually keeps the number of enzymes low DIGESTIVE ENZYME: Catalyzes the hydrolysis of compared with the protein are located in the secretions in the stomach and number of substrate pancreas molecules. Thus, in GLYCOSOL: Oxidation of glucose general, the MITOCHONDRIA: TCA Cycle (The Citric Acid) PROTEASES: Protein-splitting enzyme located in the blood; essential in clotting LYSOZYME: Catalyzes the dissolution of bacterial cell walls NAMING ENZYMES Enzymes are most commonly named by using a system that attempts to provide information about the function (rather than the structure) of the enzyme. The type of reaction catalyzed and the substrate identity are focal points for the nomenclature. A substrate is the reactant in an enzyme-catalyzed reaction. The substrate is the substance upon which the enzyme “acts.” Three important aspects of the enzyme-naming process are the following: 1. The suffix -ase identifies a substance as an enzyme. Thus urease, sucrase, and lipase are all enzyme designations. The suffix -in is still found in the names of some of the first enzymes studied, many of which are digestive enzymes. Such names include trypsin, chymotrypsin, and pepsin. 2. The type of reaction catalyzed by an enzyme is often noted with a prefix. An oxidase enzyme catalyzes an ENZYME INHIBITION oxidation reaction, and a hydrolase enzyme catalyzes a An enzyme inhibitor is a substance that slows or stops hydrolysis reaction. the normal catalytic function of an enzyme by binding to 3. The identity of the substrate is often noted in addition it. In this section, three modes by which inhibition takes to the type of reaction. Enzyme names of this type place are considered: reversible competitive inhibition, include glucose oxidase, pyruvate carboxylase, and reversible noncompetitive inhibition, and irreversible succinate dehydrogenase. Infrequently, the substrate but inhibition. not the reaction type is given, as in the names urease < DOPPELGANGER ; blocks the real substrate from getting in preventsthe enzyme fr is and lactase. In these names, the reaction involved is COMPETITIVE INHIBITOR: A competitive enzyme hydrolysis; urease catalyzes the hydrolysis of urea, inhibitor is a molecule that sufficiently resembles an lactase the hydrolysis of lactose. enzyme substrate in shape and charge distribution that it I E can compete with the substrate for occupancy of the enzyme’s active site. Thereby, preventing the binding of T - the substrate. (inserting the wrong key in the lock) NONCOMPETITIVE INHIBITOR: A noncompetitive enzyme inhibitor is a molecule that decreases enzyme activity by binding to a site on an enzyme other than the active site. Thereby, inhibits the activity of the enzyme. IRREVERSIBLE INHIBITOR: An irreversible enzyme inhibitor is a molecule that inactivates enzymes by forming a strong covalent bond to an amino acid side-chain group at the enzyme’s active site. Super glue  INDUCED FIT MODEL The size and shape of the active site cavity can change when substrate enters. The enzyme modifies the shape of the active site to accommodate the substrate. The induced fit is a result of the enzyme’s flexibility; it adapts to accept the incoming substrate. KEY TERMS TO REMEMBER It explains the specificity of enzyme action by comparing SIMPLE ENZYME: A simple enzyme is an enzyme the active site to a glove and the substrate to a hand. composed only of protein (amino acid chains). Has a flexible site where any substrate can fit CONJUGATED ENZYME: A conjugated enzyme is an in enzyme that has a non protein part in addition to a protein part. ALLOSTERIC ENZYMES: An allosteric enzyme is an enzyme with two or more protein chains (quaternary structure) and two kinds of binding sites (substrate and regulator). It is also the alternative site for the binding of the substrate, but not a priority. COFACTOR: A cofactor is the non protein part of a Both the lock-and-key model and induced-fit model conjugated enzyme that is necessary for catalytic explain the phenomenon of competitive inhibition. The function such as metallic ions. It is linked to an enzyme. inhibition molecule fits into the active site cavity in the APOENZYME: An apoenzyme is the protein part of a same way the substrate does, preventing the substrate conjugated enzyme. from entering. They emphasize the shape of the active COENZYME: It is a non protein organic cofactor site. molecule (like Vitamin B). Cases of noncompetitive inhibition can also be explained SUBSTRATE: Compound on which the enzyme works by the induced-fit model in which the binding causes a and whose reaction speeds up. change in the 3D shape of the enzyme, then there can ACTIVE SITE: It is the specific portion to which a be no catalysis. substrate binds during a reaction. ACTIVATION: It refers to any process that initiates or MECHANISM OF ACTION increases the action of enzymes. Just five of the amino acids participate in the active site in more than 65% of the enzymes studied. LOCK-AND-KEY MODEL The first model to explain the action of enzyme is the lock-and-key model. The surface that contains the active site has a restricted opening into which only one kind of substrate can fit. (only 1 substrate fit in) can In the lock-and-key model, the active site in the enzyme has a fixed, rigid geometrical conformation. Only substrates with a complementary geometry can be accommodated at such a site, much as a lock accepts only certain keys. fixed geometric shape only where It has a in. a specific substrate can fit  PROENZYME It refers to the inactive form of enzymes that must have His > Cys > Asp > Arg > Glu part of its polypeptide chain hydrolyzed and removed OW THE ENZYME REDUCES THE ACTIVATION ENERGY before it becomes active. It changes the primary and CATALYTIC POWER OF ENZYME tertiary structure. For example, trypsin (digestive It refers to how the enzyme reduces the activation enzyme) is synthesized and stored as trypsinogen (has energy is very specific to the enzyme & the reaction ni enzyme activity). Trypsinogen becomes active only being catalyzed. However, a few amino acids show up in after a six-amino acid fragment is hydrolyzed and most of the active sites. removed from the N-terminal end of its chain. PAPAIN is a protease , down which means it breaks proteins PAPAIN ISOENZYME A protease and an enzyme that clears peptide bonds. Its Isoenzymes are enzymes that occur in multiple forms; amino acids are histidine and cysteine. each catalyzes the same reaction. It can be seen in - ACTIVE SITE different places, but still in the same form. => NUCLEOPHILIC NEUTROPHILIC ATTACK It is a chemical reaction where an electron-rich atom bonds to an electron-deficient atom. ELECTRON-RICH ELECTRON-DEFICIENT# FEEDBACK MECHANISM The formation of a product inhibits an earlier reaction in T the sequence; the reaction produced by an enzyme may LDH 2, 1, 3, 4, 5 = NORMAL IN SERUM ⑨ control the activity of another, especially in the complex system in which enzymes work cooperatively. First reaction is controlled by the product ALLOSTERISM Feedback control is a process in which activation or It involves allosteric enzymes. Many, but not all, of the inhibition of the first reac- tion in a reaction sequence is enzymes responsible for regulating cellular processes controlled by a product of the reaction sequence. One are allosteric enzymes. The regulation takes place by enzyme will catalyze to produce another enzyme. means of an event that occurs at a site other than the active site, but affects the active site. Substances that bind at regulatory sites of allosteric enzymes are called regulators. The binding of a positive regulator increases enzyme activity; the shape of the active site is changed such that it can more readily accept substrates. The binding of a negative regulator (a noncompetitive inhibitor) decreases enzyme activity; changes to the active site are such that substrate is less readily accepted. BINDING OF POSITIVE BINDING OF NEGATIVE BEHAVIOR REGULATOR - increases enzyme activity - Decreases enzyme - substrate is readily accepted. activity - substrate is less readily accepted POSITIVE MODULATION: It facilitates the detachment and stimulation of an allosteric enzyme. NEGATIVE MODULATION: It inhibits allosteric enzymes. REGULATOR: Refers to the inhibitor, which is the substance that binds to an allosteric site). REGULATORY SITE: Refers to the site where it binds. KINETIC STATES T-FORM: Less active, or inactive; taudt R-FORM: Binds substrate; relax PROTEIN MODIFICATION Pyruvate kinase (PK) is the active form of the enzyme. It is inactivated by phosphorylation to pyruvate kinase phosphate (PKP). PK: active form PKP: inactive form Protein is modified for the enzyme to be activated or inactivated. ENZYMES IN MEDICINE - ALANINE AMINO TRANSFERASE-SERUM = HEPATITIS ACID PHOSPHATASE-SERUM-PROSTATE CANCER Disease ALKALINE PHOSPHATAJE-JERUM-LIVER/BONE AMYLAJE - SERUM-Mumps/panCREATIC DISEASE ASPARTATE AMINO TRANSFERASE-JERUM & (FREBROSPINAL HEART ATTACK/HEPA FLUID LDH PH ; CkP ] SERUM-HEART ATTAGR CHEM 131.1 Mr. Sio | Nucleic Acids NUCLEIC ACIDS this carbon in ribose becomes an H atom in A nucleic acid is an unbranched polymer containing 2′-deoxyribose. (The prefix deoxy- means “without monomer units called nucleotides. oxygen.”). NAKA BOND KAY PHOSPHATE GROUP AT NITROGEN-CONTAINING HETEROCYCLIC BASE , A nucleotide is a three-subunit molecule in which a NITROGENOUS BASE pentose sugar is bonded to both a phosphate group and There are five nitrogen-containing heterocyclic bases. a nitrogen-containing heterocyclic base. With a Three of them are derivatives of pyrimidine, a three-subunit structure, nucleotides are more complex monocyclic base with a six-membered ring, and two are monomers than the monosaccharides of derivatives of purine, a bicyclic base with fused five- and polysaccharides or the amino acids of proteins. six-membered rings. MAS COMPLEX SI NUCLEOTIDES MONOMERS KLAYSA MONOSSACCHARIDES POLYSACCHARIDES KAY OF Two types of nucleic acids are found within cells of higher organisms: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA: It facilitates the storage and transfer of genetic information; it is passed from existing cells to new cells during cell division. RNA: It occurs in all parts of a cell. It functions primarily MONOCYCLIC BASE WITH A BICYCLIC BASE WITH A FIVE-AND in synthesis of proteins, the molecules that carry out 6 MEMBERED RING SIX = MEMBERED RINGS essential cellular functions. PYRIMIDINE It has two nitrogen atoms and contains a single STRUCTURE OF A NUCLEIC ACID carbon-nitrogen 6-membered ring. It is a heterocyclic aromatic organic compound that has a low melting point and low boiling point. Its catabolism produces beta amino acids, plus ammonia and carbon dioxide. The three pyrimidine derivatives found in nucleotides are thymine (T), cytosine (C), and uracil (U). THYMINE: It is the 5-methyl-2,4-dioxo derivative of pyrimidine. CYTOSINE: It is the 4-amino-2-oxo derivative of PENTOSE SUGAR pyrimidine. It is the sugar unit that can either be ribose (RNA) or URACIL: It is the 2,4-dioxo derivative of pyrimidine. 2-deoxyribose (DNA). ? WITHOUT OXYGEN DNA: (A), (G), (C), (T) Structurally, the only difference between these two sugars occurs at carbon 2′. The OH group present on KB | 1  PURINE It has four nitrogen atoms and contains two carbon-nitrogen rings. It is a bicyclic base with fused 5- and 6-membered rings. It has a high melting point and high boiling point, and has secondary and tertiary structure. Its catabolism produces uric acid. The two purine derivatives found in nucleotides are adenine (A) and guanine (G). ADENINE: It is the 6-amino derivative of purine. GUANINE: It is the 2-amino-6-oxo derivative of puine. NUCLEOTIDE FORMATION S 1. Condensation, with formation of a water molecule, 8 occurs at two locations: between sugar and base (nucleoside), and between sugar and phosphate (nucleotide). 2. The base is always attached at the C-1 position of the sugar: for purine bases, attachment is through N9; for RNA: (A), (G), (C), (U) pyrimidine bases, N1 is involved. The bond connecting the sugar and base is a β-N-glycosidic linkage. DNA and RNA can attach to a sugar, forming four 3. The phosphate group is attached to the sugar at the different molecules. C-5 position through a phosphate-ester linkage. *AMINE: A nitrogen-containing compound. NOMENCLATURE 1. All names end in 5-monophosphate, which signifies the presence of a phosphate group. 2. For pyrimidine bases, the suffix -idine is used (cytidine, thymidine, uridine). For purine bases, the suffix -osine is used (adenosine, guanosine). 3. The prefix deoxy- is used to indicate that the sugar present is deoxyribose. No prefix is used when the sugar present is ribose. PHOSPHATE Example: Phosphate, the third component of a nucleotide, is dAMP — deoxyadenosine 5-monophosphate derived from phosphoric acid (H₃PO₄). Under cellular pH GMP — guanosine 5-monophosphate conditions, the phosphoric acid loses two of its hydrogen dTMP — deoxythymidine 5-monophosphate atoms to give a hydrogen phosphate ion (HPO₄). Two purine bases and three pyrimidine bases are found in the nucleotides present in nucleic acids. The abbreviations use the one-letter symbols for the base (A, C, G, T, and U), MP for monophosphate, and a lowercase d at the start of the abbreviation when deoxyribose is the sugar.  3' end -) HAS A FREE HYDROXYL GROUP RIBONUCLEIC ACID other end of the nucleotide chain, the 3′ end, normally A ribonucleic acid (RNA) is a nucleotide polymer in has a free hydroxyl group attached to the 3′ carbon which each of the monomers contains ribose, a atom. phosphate group, and one of the heterocyclic bases 3. Each nonterminal phosphate group in the backbone of adenine, cytosine, guanine, or uracil. Two changes to a nucleic acid carries a -1 charge. The parent this definition generate the deoxyribonucleic acid phosphoric acid molecule from which the phosphate was definition; deoxyribose replaces ribose and thymine derived originally had three OH groups. replaces uracil. DEOXYRIBONUCLEIC ACID A deoxyribonucleic acid (DNA) is a nucleotide polymer in which each of the monomers contains deoxyribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or thymine. The alternating sugar–phosphate chain in a nucleic acid structure is often called the nucleic acid backbone. This backbone is constant throughout the entire nucleic acid structure. For DNA molecules, the backbone consists of alternating phosphate and deoxyribose sugar units; for RNA molecules, the backbone consists of alternating phosphate and ribose sugar units. PRIMARY NUCLEIC ACID STRUCTURE Primary nucleic acid structure is the sequence in which nucleotides are linked together in a nucleic acid. Because the sugar–phosphate backbone of a given nucleic acid does not vary, the primary structure of the nucleic acid depends only on the sequence of bases present. 1. Each nonterminal phosphate group of the sugar–phosphate backbone is bonded to two sugar molecules through a 3′,5′-phosphodiester linkage. There DOUBLE HELIX is a phosphoester bond to the 5′ carbon of one sugar It involves two polynucleotide strands coiled around unit and a phosphodiester bond to the 3′ carbon of the each other in a manner somewhat like a spiral staircase. other sugar. The bases (side chains) of each backbone extend 2. A nucleotide chain has directionality. One end of the inward toward the bases of the other strand. The two nucleotide chain, the 5′ end, normally carries a free strands are connected by hydrogen bonds between their phosphate group attached to the 5′ carbon atom. The bases. Additionally, the two strands of the double helix 5 end CARRIES A FREE PHOSPHATE GROUP are antiparallel—that is, they run in opposite directions. One strand runs in the 5′-to-3′ direction, and the other is oriented in the 3′-to-5′ direction. BASE PAIRING Only pairs involving one small base (a pyrimidine) and one large base (a purine) correctly “fit” within the helix interior. There is not enough room for two large purine bases to fit opposite each other (they overlap), and two small pyrimidine bases are too far apart to hydrogen-bond to one another effectively. The pairing of A with T and that of G with C are said to be complementary. A and T are complementary bases, as are G and C. Complementary bases are pairs of bases in a nucleic acid structure that hydrogen-bond to each other. The specificity of the bases are provided by hydrogen bonds, which is the bond between bases. Complementary DNA strands are strands of DNA in a double helix with base pairing such that each base is located opposite its complementary base. Wherever G occurs in one strand, there is a C in the other strand; wherever T occurs in one strand, there is an A in the other strand. The base sequence of a single strand of a DNA molecule segment is always written in the direction from the 5′ end to the 3′ end of the segment. 5′ A–A–G–C–T–A–G–C–T–T–A–C–T 3′ 3’ T–T–C–G–A–T–C–G–A–A–T–G–A 5’ If the end designations for a base sequence (5′ and 3′) are not specified for a sequence of bases, it is assumed that the sequence starts with the 5′ end base. In the base sequence it is assumed that A is the 5′ end base. A–C–G–T–T–C BASE-STACKING INTERACTIONS This interaction gives stability to the DNA. Stacking interactions involving a given base and the parallel bases directly above and below it also contribute to the stabilization of the DNA double helix. These stacking interactions are as important in their stabilization effects as is the hydrogen bonding associated with base pairing—sometimes even more important. Purine and pyrimidine bases are hydrophobic in nature, so their stacking interac- tions are those associated with hydrophobic molecules—mainly London forces. are antiparallel—that is, they run in opposite directions. REPLICATION One strand runs in the 5′-to-3′ direction, and the other is The process by which new DNA molecules are oriented in the 3′-to-5′ direction. generated is DNA replication. DNA replication is the biochemical process by which DNA molecules produce BASE PAIRING exact duplicates of themselves. The key concept in Only pairs involving one small base (a pyrimidine) and understanding DNA replication is the base pairing one large base (a purine) correctly “fit” within the helix associated with the DNA double helix. interior. There is not enough room for two large purine bases to fit opposite each other (they overlap), and two In DNA replication, the two strands of the DNA double small pyrimidine bases are too far apart to helix are regarded as a pair of templates, or patterns. hydrogen-bond to one another effectively. During replication, the strands separate. Each can then act as a template for the synthesis of a new, f The pairing of A with T and that of G with C are said to complementary strand. The result is two daughter DNA be complementary. A and T are complementary bases, molecules with base sequences identical to those of the as are G and C. Complementary bases are pairs of parent double helix. Details of this replication are as bases in a nucleic acid structure that hydrogen-bond to follows. each other. The specificity of the bases are provided by hydrogen bonds, which is the bond between bases. Under the influence of the enzyme DNA helicase, the DNA double helix unwinds, and the hydrogen bonds Complementary DNA strands are strands of DNA in a between complementary bases are broken. In simple double helix with base pairing such that each base is terms, the DNA helicase aids in the unwinding of the located opposite its complementary base. Wherever G DNA double helix. This unwinding process is somewhat occurs in one strand, there is a C in the other strand; like opening a zipper. The point at which the DNA double wherever T occurs in one strand, there is an A in the helix is unwinding, which is constantly changing · other strand. (moving), is called the replication fork. The base sequence of a single strand of a DNA molecule segment is always written in the direction from the 5′ end to the 3′ end of the segment. 5′ A–A–G–C–T–A–G–C–T–T–A–C–T 3′ 3’ T–T–C–G–A–T–C–G–A–A–T–G–A 5’ If the end designations for a base sequence (5′ and 3′) are not specified for a sequence of bases, it is assumed that the sequence starts with the 5′ end base. In the The enzyme DNA polymerase then verifies that the base sequence it is assumed that A is the 5′ end base. base pairing is correct and catalyzes the formation of a new phosphodiester linkage. A–C–G–T–T–C Remember, 1 template makes 1 daughter strand. BASE-STACKING INTERACTIONS This interaction gives stability to the DNA. Stacking The enzyme DNA polymerase can operate on a forming interactions involving a given base and the parallel DNA daughter strand only in the 5′-to-3′ direction. bases directly above and below it also contribute to the Because the two strands of parent DNA run in opposite stabilization of the DNA double helix. These stacking directions (one is 5′ to 3′ and the other 3′ to 5′), only one interactions are as important in their stabilization effects strand can grow continuously in the 5′-to-3′ direction. as is the hydrogen bonding associated with base pairing—sometimes even more important. The other strand must be formed in short segments, called Okazaki fragments, as the DNA unwinds. The Purine and pyrimidine bases are hydrophobic in nature, breaks or gaps in this daughter strand are called nicks. so their stacking interac- tions are those associated with To complete the formation of this strand, the Okazaki hydrophobic molecules—mainly London forces. fragments are connected by action of the enzyme DNA ligase. The strand that grows continuously is called the These histone–DNA complexes are called leading strand, and the strand that is synthesized in chromosomes. A chromosome is an individual DNA small segments is called the lagging strand. molecule bound to a group of proteins. Typically, a chromosome is about 15% by mass DNA and 85% by The unwinding usually occurs at several interior mass protein. locations simultaneously and DNA replication is bidirectional for these locations; that is, it proceeds in Chromosomes occur in matched (homologous) pairs. both directions from the unwinding sites. The 46 chromosomes of a human cell constitute 23 homologous pairs. Homologous chromosomes have The result of this multiple-site replication process is the similar, but not identical, DNA base sequences (same formation of “bubbles” of newly synthesized DNA. The structure). bubbles grow larger and eventually coalesce, giving rise to two complete daughter DNAs. PROTEIN SYNTHESIS The overall process of protein synthesis is divided into two phases. The first phase is called transcription and the second translation. Four major differences exist between RNA molecules and DNA molecules: 1. The sugar unit in the backbone of RNA is ribose; it is deoxyribose in DNA. 2. The base thymine found in DNA is replaced by uracil DNA REPLICATION SUMMARY in RNA. In RNA, uracil, instead of thymine, pairs with (forms hydrogen bonds with) adenine. 3. RNA is a single-stranded molecule; DNA is double-stranded (double helix). Thus RNA, unlike DNA, does not contain equal amounts of specific bases. 4. RNA molecules are much smaller than DNA molecules, ranging from 75 nucleotides to a few thousand nucleotides. TYPES OF RNA MOLECULES These five RNA types are heterogeneous nuclear RNA (hnRNA), messenger RNA (mRNA), small nuclear RNA (snRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). hnRNA: Heterogeneous nuclear RNA (hnRNA) is the RNA formed directly by DNA transcription. *Post-transcription processing converts the heterogeneous nuclear RNA to messenger RNA. CHROMOSOMES mRNA: Messenger RNA (mRNA) is RNA that carries Once the DNA within a cell has been replicated, it instructions for protein synthesis (genetic information) to interacts with specific proteins in the cell called histones the sites for protein synthesis. to form structural units that provide the most stable arrangement for the long DNA molecules.  & ALL THE TOTAL DNA IN A CHROMOSOME snRNA: Small nuclear RNA (snRNA) is RNA that A genome, however, is all of the genetic material (the facilitates the conversion of heterogeneous nuclear RNA total DNA) contained in the chromosomes of an to messenger RNA. organism. rRNA: Ribosomal RNA (rRNA) is RNA that combines STEPS IN THE TRANSCRIPTION PROCESS with specific proteins to form ribosomes, the physical 1. A portion of the DNA double helix unwinds, exposing sites for protein synthesis. *The rRNA present in DNA a sequence of bases (a gene). The unwinding process is ribosomes has no informational function. UNWINDINGgoverned by the enzyme RNA polymerase rather than by DNA helicase (replication enzyme). tRNA: Transfer RNA (tRNA) is RNA that delivers amino BASE PAIRING acids to the sites for protein synthesis. *Transfer RNAs 2. Free ribonucleotides, one nucleotide at a time, align are the smallest of the RNAs. along one of the exposed strands of DNA bases, the template strand, forming new base pairs. In this process, The process of DNA transcription occurs in the nucleus, U rather than T aligns with A in the base-pairing process. as does the processing of hnRNA to mRNA. (*DNA Only about 10 base pairs of the DNA template strand are replication also occurs in the nucleus.) The mRNA exposed at a time. Because ribonucleotides rather than formed in the nucleus travels to the cytoplasm where deoxyribonucleotides are involved in the base pairing, translation (protein synthesis) occurs. ribose, rather than deoxyribose, becomes incorporated into the new nucleic acid backbone. In DNA—RNA base pairing, the complementary base pairs are, RNA A—U - G — C AGCU - DNA T—A C — G AGCT - RNA BUILDING 3. RNA polymerase is involved in the linkage of ribonucleotides, one by one, to the growing hnRNA TRANSCRIPTION: RNA SYNTHESIS molecule. Transcription is the process by which DNA directs the ENDING TRANSCRIPTION synthesis of hnRNA/mRNA molecules that carry the 4. Transcription ends when the RNA polymerase coded information needed for protein synthesis. enzyme encounters a sequence of bases that is “read” Messenger RNA production via transcription is actually a as a stop signal. The newly formed hnRNA molecule and “two-step” process in which an hnRNA molecule is the RNA polymerase enzyme are released, and the DNA initially produced and then is “edited” to yield the desired then rewinds to reform the original double helix. mRNA molecule. The mRNA molecule so produced then functions as the carrier of the information needed to direct protein synthesis. During transcription, a DNA molecule unwinds, under enzyme influence, at the particular location where the appropriate base sequence is found for the hnRNA/mRNA of concern, and the “exposed” base sequence is transcribed. GENE A short segment of a DNA strand so transcribed, which POST-TRANSCRIPTION: FORMATION OF mRNA contains instructions for the formation of a particular The conversion of hnRNA to mRNA involves hnRNA/mRNA, is called a gene. A gene is a segment of post-transcription processing of the hnRNA. a DNA strand that contains the base sequence for the production of a specific hnRNA/mRNA molecule. TO FORM A SHORTENED RNA STRAND EXONS: These are gene segments that contain and TRANSCRIPTOME convey information. The total number of mRNA molecules for an organism is INTRONS: These are gene segments that do not convey known as its transcriptome. A transcriptome is all of the (code for) information. mRNA molecules that can be generated from the genetic material in a genome. It differs from a genome in that it Both the exons and the introns of a gene are transcribed acknowledges the biochemical complexity created by during production of hnRNA. The hnRNA is then splice variants obtained from hnRNA. “edited,” under enzyme direction, to remove the introns, and the remaining exons are joined together to form a GENETIC CODE shortened RNA strand that carries the genetic The genetic code is the assignment of the 64 mRNA information of the transcribed gene. The removal of the codons to specific amino acids (or stop signals) by introns and joining together of the exons takes place Marshall Nirenberg and Har Gobind who were awarded simultaneously in a single process. with the 1968 Nobel Prize in Chemistry. Such three-nucleotide sequences are called codons. A codon The “edited” RNA so produced is the messenger RNA is a three-nucleotide sequence in an mRNA molecule (mRNA) that serves as a blueprint for protein assembly. that codes for a specific amino acid. There are 64 codons to choose from. SPLICING Splicing is the process of removing introns from an hnRNA molecule and joining the remaining exons together to form an mRNA molecule. The splicing process involves snRNA molecules, most recent of the RNA types to be discovered. This type of RNA is never found “free” in a cell. An snRNA molecule is always found complexed with proteins in particles called small nuclear ribonucleoprotein particles, which are usually called snRNPs (pronounced “snurps”). A small nuclear ribonucleoprotein particle is a complex formed from an snRNA molecule and several proteins. “Snurps” always further collect together into larger complexes called spliceosomes. A spliceosome is a large assembly of snRNA molecules and proteins It was found that 61 of the 64 codons formed by various involved in the conversion of hnRNA molecules to combinations of the bases A, C, G, and U were related mRNA molecules. to specific amino acids; the other three combinations were termination codons (“stop” signals) for protein ALTERNATIVE SPLICING synthesis. Alternative splicing is a process by which several different proteins that are variations of a basic structural Characteristics of Genetic Code: motif can be produced from a single gene. In alternative 1. The genetic code is highly degenerate; that is, many splicing, an hnRNA molecule with multiple exons present amino acids are designated by more than one codon. is spliced in several different ways. Codons that specify the same amino acid are called synonyms. 2. There is a pattern to the arrangement of synonyms in the genetic code table. 3. The genetic code is almost universal. 4. An initiation codon exists. ANTICODONS & tRNA The amino acids used in protein synthesis do not directly interact with the codons of an mRNA molecule. Instead, tRNA molecules function as intermediaries that deliver amino acids to the mRNA. At least one type of tRNA The substances needed for the translation phase of molecule exists for each of the 20 amino acids found in protein synthesis are: proteins. – mRNA molecules – tRNA molecules All tRNA molecules have the same general shape, and – amino acids, ribosomes this shape is crucial to how they function. A general – number of different enzymes two-dimensional “cloverleaf” is the shape of a tRNA molecule, a shape produced by the molecule’s folding A ribosome is an rRNA–protein complex that serves as and twisting into regions of parallel strands and regions the site for the translation phase of protein synthesis. of hairpin loops. 3'end · - where amino acid attaches The structure of a ribosome: with mRNA – They contain four rRNA molecules and about 80 · Anticodon loop-matches up proteins that are packed into two rRNA–protein subunits, one small subunit and one large subunit. – Each subunit contains approximately 65% rRNA and 35% protein by mass. – A ribosome’s active site, the location where proteins are synthesized by one-at-a-time addition of amino acids to a growing peptide chain, is located in the large ribosomal subunit. – The active site is mostly rRNA, with only one of the ribosome’s many protein components being present. TRANSLATION PROCESS 1. ACTIVATION OF tRNA First, an amino acid interacts with an activator molecule The 3′ end of the open part of the cloverleaf structure is to form a highly energetic complex. This complex then where an amino acid covalently bonds to the tRNA. The reacts with the appropriate tRNA molecule to produce an carboxyl group of the amino acid reacts with the 3′ OH activated tRNA molecule, a tRNA molecule that has an group on the terminal nucleotide residue resulting in the amino acid covalently bonded to it at its 3′ end through formation of an aminoacyl ester. Each of the different an ester linkage. tRNA molecules is specifically recognized by an aminoacyl tRNA synthetase enzyme. These enzymes also recognize the one kind of amino acid that “belongs” with the particular tRNA and facilitates its bonding to the tRNA. The loop opposite the open end of the cloverleaf, called the anticodon loop, consists of seven unpaired bases of which the middle three bases constitute the anticodon. This anticodon recognizes and base pairs with an mRNA codon that possesses a complementary three-base unit. 2. INITIATION An anticodon is a three-nucleotide sequence on a tRNA The initiation of protein synthesis in human cells begins molecule that is complementary to a codon on an mRNA when mRNA attaches itself to the surface of a small molecule. ribosomal subunit such that its first codon, which is always the initiating codon AUG (methionine), occupies TRANSLATION a site called the P site (peptidyl site). Translation is the process by which mRNA codons are deciphered and a particular protein molecule is An activated tRNA molecule with an anticodon synthesized. complementary to the codon AUG attaches itself, through complementary base pairing, to the AUG codon.  The movement of a ribosome along an mRNA molecule is called translocation. Translocation is the part of translation in which a ribosome moves down an mRNA molecule three base positions (one codon) so that a new codon can occupy the ribosomal A site. 3. ELONGATION Next to the P site in an mRNA–ribosome complex is a second binding site called the A site (aminoacyl site). At this second site the next mRNA codon is exposed, and a The third codon, now at the A site, accepts an incoming tRNA with the appropriate anticodon binds to it. tRNA with its accompanying amino acid; then the entire dipeptide at the P site is transferred and bonded to the A site amino acid to give a tripeptide. The transfer of the growing peptide chain from the P site to the A site is an example of an acyl transfer reaction. It is the transfer of the growing polypeptide chain from the P site to the A site. 4. TERMINATION The polypeptide continues to grow by way of translocation until all necessary amino acids are in place (parang isang continuous process, after ng isang codon and bonded to each other. Appearance in the mRNA sa isang site, dun naman sa next na site para tuloy codon sequence of one of the three stop codons (UAA, tuloy) UAG, or UGA) terminates the pro- cess. No tRNA has an anticodon that can base pair with these stop codons. With amino acids in place at both the P and the A sites, The polypeptide is then cleaved from the tRNA through the enzyme peptidyl transferase effects the linking of the hydrolysis. *The stop codons are UAA, UAG, and UGA. P site amino acid to the A site amino acid to form a dipeptide. Such peptide bond formation leaves the tRNA POST-TRANSLATION PROCESS at the P site empty and the tRNA at the A site bearing Happens after a protein is formed. This post-translational the dipeptide. (yung amino acid sa P site i-aattach niya processing gives the protein the final form it needs to be sa amino acid na nasa A site para magkaroon ng fully functional. dipeptide bonding or dipeptide chains; in simple terms, dinidikit niya yung amino acids sa dalawang site) The empty tRNA at the P site now leaves that site and is free to pick up another molecule of its specific amino acid. Simultaneously with the release of tRNA from the P site, the ribosome shifts along the mRNA. This shift puts the newly formed dipeptide at the P site, and the third codon of mRNA is now avail- able, at site A, to accept a tRNA molecule whose anticodon complements this codon.  MUTAGEN: RADIATION Radiation, in the form of ultraviolet light, X-rays, radioactivity, and cosmic rays, has the potential to be mutagenic. Ultraviolet light from the sun is the radiation that causes sunburn and can induce changes in the DNA of skin cells. Sustained exposure to ultraviolet light can lead to skin cancer problems. MUTAGEN: CHEMICAL Nitrous acid (HNO2) is a mutagen that causes deamination of heterocyclic nitrogen bases. For example, HNO2 can convert cytosine to uracil. Deamination of a cytosine that was part of an mRNA codon would change the codon; for example, CGG would become UGG. EFFICIENCY OF mRNA UTILIZATION Nitrites, nitrates, and nitrosamine can all be nitrous acid. Many ribosomes can move simultaneously along a These can be seen in processed foods, like hotdogs. single mRNA molecule. This multiple use of mRNA molecules reduces the amount of resources and energy NUCLEIC ACIDS AND VIRUSES that the cell expends to synthesize needed protein. Such A virus is a small particle that contains DNA or RNA (but complexes of several ribosomes and mRNA are called not both) surrounded by a coat of protein and that polyribosomes or polysomes. A polyribosome is a cannot reproduce without the aid of a host cell. These complex of mRNA and several ribosomes. are very small disease-causing agents that are considered the lowest order of life. Viruses do not possess the nucleotides, enzymes, amino acids, and other molecules necessary to replicate their nucleic acid or to synthesize proteins. *The only function of a virus is to replicate, but NOT by themselves; viruses do not generate energy. (*Imagine, a virus is surrounded by a coat and yun yung nagpoprotect sa kaniya. Hindi nila kaya magproduce, *The small subunits will continuously attach to the kaya they infect other living things para i-inject nila yung mRNA bases, so there will be tRNA formed continuously genome or genetic info nila dun sa cell at yung cell na for it to attach to the large subunit and form different mismo magrereplicate nung DNA nila for them.) proteins/strands until a complex chain is formed. DNA VIRUS: The host cell replicates the viral DNA in a MUTATION manner similar to the way it replicates its own DNA. The A mutation is an error in base sequence in a gene that is newly produced viral DNA then proceeds to make the reproduced during DNA replication. Such errors alter the proteins needed for the production of protein coats for genetic information that is passed on during transcription additional viruses. This includes herpes, smallpox, (sa transcription palang sira na). The altered information hepatitis B, adenoviruses, and warts. can cause changes in amino acid sequence during protein synthesis. Sometimes, such changes have a PaPaAdPoHeHe profound effect on an organism. Pa: Papova Pa: Parvo It can be triggered by a mutagen. A mutagen is a Ad: Adeno substance or agent that causes a change in the structure Po: Pox (smallpox) of a gene and can either be a chemical or radiation He: Heladna agent. He: Herpes RNA VIRUS: An RNA-containing virus is called a retrovirus. Once inside a host, such viruses first make viral DNA. This reverse synthesis is governed by the enzyme reverse transcriptase. The template is the viral RNA rather than DNA. The viral DNA so produced then produces additional viral DNA and the proteins necessary for the protein coats. This includes polio virus, retrovirus, influenza, virus, missiles, mumps, and hepatitis E. *RNA will be converted to DNA first. VACCINE: A vaccine is a preparation containing an inactive or weakened form of a virus or bacterium. The antibodies produced by the body against these specially modified viruses or bacteria effectively act against the naturally occurring active forms as well. BSMT 2A ENZYME DISEASES – VIRAL HEPATITIS HEPATITIS A (Picornaviridae) Liver - One of the most common type along hepa B and C - Regulator of most chemical levels in the blood and - Highly infectious, rarely fatal excretes a product called bile - Young children are usually asymptomatic; adults - Numerous vital functions of production, are more likely to have symptoms (still left conversion, and regulation. unexplained) Hepatic lobule A. INCUBATION PERIOD: 15-50 days (28 days - Functional unit of the liver; about 50,000 to average) 100,000 lobules - Made up of liver cells (hepatocytes) B. MODE OF TRANSMISSION - Primarily through contaminated food/drink (can LIVER ENZYMES (not all) happen at any point) ➔ Alanine aminotransferase (ALT/SGPT) - found in - Spread from close, personal contact w/ an infected the cytoplasm person ➔ Aspartate aminotransferase (AST/SGOT) - found in cytoplasm, mitochondria C. SYMPTOMS ➔ Alkaline phosphatase (ALP) - found in canaliculi Prodromal phase ➔ Gamma Glutamyl transpeptidase (GGT) - found in canaliculi Fever Malaise Vomiting ➔ Lactate Dehydrogenase (LDH) - found in mitochondria Nausea Diarrhea HEPATITIS Icteric phase - General term for liver inflammation - Over 325 million suffers from hepatitis infection Jaundice Dark urine Pale stool - Majority are hepatitis B Hepatomegaly Increase liver TYPES OF HEPATITIS (cause-based) enzymes ❖ Viral - infectious, w/ virus - Hepatitis A - E Convalescent phase ❖ Non-viral - non-infectious - Toxic hepatitis Recovery phase - Drug-induced hepatitis ❖ Other types - Autoimmune hepatitis D. PREVENTION AND TREATMENT - Alcoholic hepatitis - No specific treatment, body will recover on its own - Non-alcoholic steatohepatitis (NASH) for several weeks/months - Need of medical follow up of liver functions - Personal hygiene (handwashing) ENTRY AND REPLICATION (HEPA A,C,D,E) - Food hygiene - Potable water source - Hepatitis A vaccine (pre and post exposure) General pathophysiology of Hepa A,C,E All types of hepatitis except Hepa B (DNA) are single stranded RNA 1. Binds to the receptors on the surface of hepatocyte 2. Entry through endocytosis and released in cytosol 3. Translation and proteolytic cleavage/processing 4. RNA replication of the virus (varies) 5. Assembly of hepatitis virus particles and formation of virions 6. Maturation of virus and release into the extracellular compartments Bambico, Cabalod, Ceperez, Diaz, Ibanez, Lababit, Madrid, Pineda, Rayos, Sarmiento, Tarroza, Umali, Yangco BSMT 2A HEPATITIS B (Hepadnaviridae) Hepatomegaly Increase liver enzymes - Can be acute/chronic disease Convalescent phase - Can increase chance of mortality from cirrhosis and liver cancer Recovery phase - A double stranded DNA type of virus Antigen particles Chronic infection: HBsAg - hepatitis B surface antigen - 10-30% of HBsAg carriers who develop hepatitis HBcAg - hepatitis B core antigen are often symptomatic HBeAg - hepatitis B e antigen Extrahepatic manifestations: INCUBATION PERIOD: 40 - 150 days - Arthritis - Myocarditis a. PATHOPHYSIOLOGY - Pericarditis - Glomerulonephritis Hepatitis B is an enveloped virus, partially double stranded DNA virus. Replicates via reverse transcriptase. d. DIAGNOSIS For adults: triple panel test once in their lifetime 1. HBV enters hepatocyte through endocytosis Infants: mechanism For newborns: HBsAg and anti-HBs seromarkers 2. Once inside, it will uncoat and releases the envelope, proteins Triple-panel test: HBsAg, Anti-HBs, total antibody to 3. Partially double stranded DNA molecule releases hepatitis B core antigen to the nucleus of the cell 4. The partially double stranded DNA molecule of the e. PREVENTION AND TREATMENT virus has an enzymes within a nucleus which - Vaccination (most effective way) converts it to double stranded DNA, and that is - Blood safety (blood used in transfusions are tested RNA polymerases that transcribe to RNA thoroughly) 5. RNA molecule converted to pre genomic RNA - Education and awareness 6. pG-RNA helps in viral amplification and replication - Personal hygiene because hepa B is a retrovirus that has their own - Safe sex practices enzyme; reverse transcriptase - NO needle sharing 7. Reverse transcriptase converts pG-RNA into DNA making it the nucleic substance needed ACUTE TREATMENT 8. The DNA converts double stranded DNA 1. Healthy eating habits, hydration of water, taking molecules but only partially. This pDSDNA can some analgesics (recommended by doctors) combined with the vesicles containing the proteins synthesised producing a whole new HBV If symptoms persist: 9. New HBV released to cell through exocytosis 2. IV fluids, IV nutrition, Pain relief b. MODE OF TRANSMISSION CHRONIC TREATMENT - Parenteral (subcutaneous, intravenous, 1. Surveillance (blood tests, imaging tests, intramuscular) elastography) - Contact with infected person’s blood, sperm, or 2. Medication:most effective with active liver disease other bodily fluids - Immune modulators: peginterferon (given 6-12 months) c. SYMPTOMS (acute infection) - Oral antivirals: tenofovir, entecavir 3. Surgery : needed for complications like cirrhosis/liver cancer Prodromal phase - Partial resection: removal of part of the liver Fever Malaise Vomiting - Liver transplant: necessary if the liver is severely damaged Nausea Diarrhea Icteric phase Jaundice Dark urine Pale stool Bambico, Cabalod, Ceperez, Diaz, Ibanez, Lababit, Madrid, Pineda, Rayos, Sarmiento, Tarroza, Umali, Yangco BSMT 2A - Use serum (common) or plasma HEPATITIS C (flaviviridae) - Detect anti-HCV antibodies 4-6 weeks after infection - Can be both acute and chronic hepatitis - Acute HCV are usually asymptomatic and not fatal - NUCLEIC ACID TESTING (NAT) - Early detection and treatment prevents from - May use serum or plasma serious liver damage and improve long term health - Blood test used to detect HCV RNA INCUBATION PERIOD: 2 weeks to 6 months e. PREVENTION AND TREATMENT a. MODE OF TRANSMISSION - No effective vaccine against hepatitis C - Parenteral - Personal hygiene - Mother to baby - Safe handling of sharps/biomedical wastes - Sexual practices - Screening of blood before transfusion - Safe sex practices b. SYMPTOMS Direct-acting antiviral tablets (DAA) - Safest and most effective medicine for treating Prodromal phase hepatitis C - Recommended therapy by WHO for 3 years and Fever Malaise Vomiting above - Effective at clearing infection in more than 90% of Nausea Diarrhea people Icteric phase - Taken for 8-12 weeks - Costly Jaundice Dark urine Pale stool Hepatomegaly Increase liver enzymes Convalescent phase Recovery phase c. CLINICAL DESCRIPTIONS Acute Hepatitis C - Duration is 1-26 weeks - Asymptomatic or mild symptoms - Aminotransferases are rarely higher than 1000 u/L Chronic Hepatitis C - When acute HCV persist more than 6 months - Happens to 75% of patients - 15-30% of patients progress to cirrhosis after decades Extrahepatic Complications - Diseases on other organs associated with hepatitis - 30-40% of patients develop this Examples: autoimmune diseases, dermatologic conditions, renal and cardiovascular diseases, metabolic syndromes HCV and HIV co-infections - 15-30% of HIV patients are infected with HCV due to shared risk factors d. DIAGNOSIS - ELISA (enzyme-linked immunoassays) Bambico, Cabalod, Ceperez, Diaz, Ibanez, Lababit, Madrid, Pineda, Rayos, Sarmiento, Tarroza, Umali, Yangco BSMT 2A HEPATITIS D (Deltaviridae) HEPATITIS E (hepeviridae) - Occurs only in those infected with HBV - HEV outbreaks are common in developing - An RNA virus and a unique type of virus known as countries like in south asian countries. satellite virus - A non-enveloped ssRNA virus INCUBATION PERIOD : 2-8 weeks INCUBATION PERIOD: 15-50 days (28 days average) a. MODE OF TRANSMISSION a. MODE OF TRANSMISSION - Parenteral - Faecal-oral route - Mother to baby - Close contact transmission - Sexual practices - Almost exclusively acute infection b. SYMPTOMS b. SYMPTOMS Prodromal phase Prodromal phase Fever Malaise Vomiting Fever Malaise Vomiting Nausea Diarrhea Nausea Diarrhea Icteric phase Icteric phase Jaundice Dark urine Pale stool Jaundice Dark urine Pale stool Hepatomegaly Increase liver Hepatomegaly Increase liver enzymes enzymes Convalescent phase Convalescent phase Recovery phase Recovery phase c. TYPES OF INFECTIONS c. DIAGNOSIS 1. Co-infection (acute HBV + HDV): Lower chance of - Detected by either the presence of RNA of HEV or becoming chronic the antibodies against the virus in the serum, stool 2. Superinfection (chronic HBV + new HDV): high or in the liver. risk of progressing to chronic HDV with more severe liver diseases. Key serologic markers: anti-HEV IgM, anti-HEV IgG, HEV RNA d. PREVENTION AND TREATMENT - Vaccination (HBV) d. PREVENTION AND TREATMENT - Personal hygiene - Proper water sanitation and waste disposal - Safe sex practices - Proper personal hygiene - NO needle sharing - No treatment, but hospitalisation is needed for Px that has fulminant hepatitis & symptomatic Hepatitis B immunization does not protect against HDV in pregnant women. individuals already infected with HBV Pegylated interferon alpha - Have side effects - Not recommended for: decompensated cirrhosis, active psychiatric conditions, autoimmune diseases. Bulevirtide - Promising treatment for hepa D Medicines used for hepa B is also applicable to hepa D Bambico, Cabalod, Ceperez, Diaz, Ibanez, Lababit, Madrid, Pineda, Rayos, Sarmiento, Tarroza, Umali, Yangco SUMMARY Amino aciduria is a condition where abnormal amounts of amino acids are excreted in the urine. 3 DISEASES ASSOCIATED TO AMINO ACIDURIA Maple Syrup Cystinosis: Fanconi Syndrome: Urine Disease: affects lysosomal proximal tubule body’s ability to storage abnormality break down certain branch-chain amino acids (valine, leucine, and Isolecine.) Mode of Autosomal autosomal autosomal Transmission recessive recessive recessive inheritance inheritance (primary) & acquired (secondary) Stages/Types 1. Classic 1. Infantile There are no 2. Intermediate Nephropathic specific types or 3. Intermittent Cystinosis stages but has 4. Thiamine-res 2. Juvenile or two classification: ponsive Intermediate Hereditary Cystinosis fanconi 3. Ocular or syndrome Non-nephropa Acquired thic Cystinosis fanconi syndrome Biochemical Defect of amino Intracellular cystine Failure Abnormaliti acid metabolism accumulation due reabsorption of es due to the to defective amino acids, abnormal activity lysosomal transport glucose, of the phosphate, and branched-chain bicarbonate alpha-ketoacid due to proximal dehydrogenase tubular (BCKDC or dysfunction, often BCKDH) secondary to other complex. Polydipsia diseases like Symptoms and polyuria cystinosis Neurological Electrolyte Behavioral imbalances Children:  Symptoms - vomiting failure to thrive lethargy, dehydration growth poor feeding, rickets retardation vomiting, Photophobia rickets irritability (juvenile) Characteristi Cystine Adults: c Odor - crystals osteomalacia accumulate accumulating muscular metabolites in the cornea weakness lead to (ocular) maple syrup odor in urine, sweat, and earwax Neurological Crisis - seizure comatose and brain edema Diagnosis Newborn Clinical Urine Test screening through assessment Blood tests blood tests that Check for Genetic measure levels of WBC cystine testing branched-chain levels CTNS amino acids, high genetic levels of leucine, testing isoleucine, and Eye valine Examination Autosomal recessive Inheritance = mutated gene should be carried not by only one parent but both parents.  GROUP 3 - BIOCHEM LEC Symptoms of Tay-Sachs disease generally appear between 3 to 6 months of age, and life expectancy Leader: rarely extends beyond early childhood, typically Ferrer, Francine concluding by the age of 4 or 5. Members: Juvenile Tay-Sachs Aguilar, Christian Paul T. Alvarez, Andrei C. Also inherited in an autosomal recessive manner; Andaya, Jhaszmin Lorren D. requires both parents to be carriers of the Belmonte, Lance R. mutated gene Iraula, Andrea M. Symptoms are less severe than in the infantile Ocmer, Zafirah Xaria R. form and progress more slowly Oño, Leslie Ayeza Kate A. Individuals who possess the disease may live into Pascual, Cristine Julyana E. adolescence or