1. protein denaturation
    • disruption of secondary, tertiary and quaternary structure of proteins
    • -any change in shape of the protein that causes loss of function, can be subtle or dramatic
    • *denaturing agents:
    • pH: you can change the folding which causes the refolding of prodteins to form a more stable structure
    • Temp: will denature many proteins; lowe the temperature, it is irreversible
    • Urea: common concentration is 8 molar
    • Organic solvent: amorphous
    • Heavy metal ions: lead with SH groups and form bonds that are so tight they are practically covalent
    • Detergents: antipathic molecules rot the protein structure
  2. column chromatography
    • separates protein components based upon size, charge and/or binding affinities to known ligands
    • -involves crude extract formation usually via tissue homogenization and differential centrifugation
  3. fractination
    separation of components using different types of columns
  4. Ion exchange chromatography
    • poteins are mostly cationic
    • cation exchangers have negatively charged beads; cations exchange anions
    • anion exchangers have positively charged beads; anions exchange cations
  5. size exclusion chromatography
    • beads contain pores with a diameter designed for the presumed size of proteins of interest
    • inappropriately sized proteins are eluted first while the protein of interest in later fractions
    • small proteins are eluted last irrelevant to their charge
  6. affinity chromatography
    • based on ligand-protein interactions
    • beads are coated with ligand that the protein of interest may interact with
    • proteins with no affinity for the ligand are eluted first
  7. immunoaffinity chromatography
    ligand is an antibody and the target protein is the antigen itself
  8. Sodieum dodecyl sulfate (SDS)
    • SDS poly acrylamide gel electrophoresis
    • 1sds molecule interacts with 2 aa
    • Uniform negative charge given to all proteins causing migration away from anode and twoards cathode
    • separates protein on the basis of their masses with large proteins or protein subunits migrating slowly
    • is a detergent; for every molecule, you have four times of sds - side charges are so negative they are irrelevant
    • only difference between proteins is their size and will migrate as well according to size
  9. Trypsin cleaves
    • at lysine and arginine
    • is a digestive enzyme that is used to cleave protein into fragments and does so by cleaving on the carboxyl side
    • each protease will cleave at specific aa residues on specific sides of aa
  10. Mass spectroscopy of peptides
    • based entirely on their size
    • 1 microliter contains 1 peptide
    • enough energy to break the peptide at only one place
    • loss of aa is from n - terminus
  11. hemoprotein
    • group is specialzed proteins that contain heme as a tightly bound prosthetic group
    • role of the heme group is dictated by the environment created by the 3 dimentional structure of protein
    • functions as a electron carrier in cytochromes. heme group is part of the active site of catalase which catalyzes the breakdown of H2O2
    • *heme group serves to bind oxygen reversibly in hemoglobin and myoglobin
  12. heme
    • consists of a planar porphyrin ring with an iron in the center
    • iron can form 6 bonds:
    • *4 with nitrogens of the poryphyrin ring
    • *1 with a histidine residue of globin chain
    • *1 available for oxygen
  13. myoglobin
    • a monmeri heme protein found in skeletal and heart muscle
    • interior is composed of almost entirely of non-polar aa and stabilized by hydrophobc interactions
    • charged aa are located mostly on the surface and can form hydrogen bonds with water
    • polar ones are on the surface
    • distal histidine - away
    • crevice that almost completely encloses a heme group
    • cleft contains 2 histidine residues
    • *proximal histidine (His F8) - binds directly to the iron in heme
    • *distal histidine (His E7) - function not clear yet
    • a phe residue is alos at the surface of the cleft helping to hold the heme in place
  14. hemoglobin
    • tetrameric hemoprotein found exclusively in erythrocytes
    • -4 polypeptide chains consist of 2 each of 2 different aa sequences and each has a heme prosthetic group identical to that described for myoglobin
    • held together by inter-chain hydrophobic interactions, ionic interactions, hydrogen bonds
  15. myoglobin and the beta subunits of hemoglobin
    have almost identical secondary and tertiary structures
  16. Taut (t) tense state
    • low oxygen affinity
    • resists the binding of oxygen
    • deoxygenated
  17. Relaxed (r) state
    • high oxygen affiinity
    • binding of oxygen is facilitated
    • oxygenated
  18. binding of oxygen to one heme of hemoglobin leads to
    • changes in confirmation at the subunit surface
    • a new set of binding interacions between adjacent subunits which are associated with disruption of salt bridges and formation of new hydrogen bonds and new hydrophobic interactions
    • increased affinity of the hemoglobin molecule for subsequent oxygen molecules
  19. difference in function between myoglobin and hemoglobin
    • stems from their difference in structure
    • myoglobin - can bind only 1 molecule of oxygen because contains only 1 heme group
    • hemoglobin - can bin 1 oxygen molecule at each of its 4 heme groups
  20. Oxygen binding curve (oxygen dissociation curve or oxygen saturation curve)
    a plot of the degree of saturation (y) of the oxygen binding sites measured at different partial pressures of oxygen
  21. function of myoglobin
    • binds oxygen released by hemoglobin at the low pO2 found in the muscle
    • releases oxygen within the muscle cells in response to oxygen demand
    • using ATP - oxidative phosphorylation
  22. function of hemoglobin
    • transports O2 from the lung to peripherial tissues
    • transports carbon dioxide and protons from peripheral tissues to the lung for subsequent excretion
    • O2 from lung to peripheral tissues
    • CO2 and protons peripheral to lungs
  23. hemoglobin demonstrates cooperativity
    • allows hemoglobin to deliver more oxygen to the tissues in response to relatively small changes in the partial pressure of oxygen
    • the lower p50, the highter the affinity for oxygen
  24. chloride shift
    anionic chloride ions flow into the cell to compensate for the loss of anionic bicarbonate from the cell to maintain electrical neutrality
  25. binding of ligands other than oxygen affects
    hemoglobin's oxygen binding properties
  26. H+
    • decrease in pH is the same as increase in H+; favors the protonationof an important histidine residue causing the reformation of salt bridges stabilizing the deoxy form of hemoglobin
    • facilitates the relaese of oxygen
    • overall the increase in proton concentration stailizes the doxy (T) form and promotes oxygen release
  27. CO2
    • reacts with the amino terminal alpha amino group of hemoglobin forming a carbamate and release protons
    • conversion of amino terminal from a positive to a negative charge favors salt bridges formation between the alpha and beta chains, a situation characteristic of the deoxy state
    • hemoglobin affinity for oxygen is decreased by CO2 binding
  28. Bohr's effect
    • increased concentrations of protons and carbon dioxide decrease oxygen affinity, assisting delivery of oxygen to the tissues
    • oxygen affinity of oxyhemoglobin is decreased in the presence of high levels of CO2 and a low pH
  29. 2,3 bisphosphoglycerate
    • important for normal oxygen transport function of hemoglobin
    • permits greater unloading of oxygen in capillaries of tissues
    • hemoglobin deficient in 2,3 bisphosphoglycerate acts as an "oxygen trap" rather than an oxygen transport system
  30. chronic hypoxia
    2,3 bisphoglycerate concentration increases in response
  31. adding inosine to the storage medium
    concentration decreases in blood stored in acid - citrate dextrose
  32. CO poisoning
    • binds tightly but reversibly to the hemoglobin iorn forming carbon monoxyhemoglobin (HbCO)
    • shifts hemoglobin to relaxed conformation causing the remaining heme sites to bind oxygen with high affinity
    • shifts the curve to the left
    • changes te normal sigmoidal shape toward the hyperbola
    • 50% CO-Hb is lethal mainly because CO has poisoned cytochrome oxidases
    • affected hemoglobin releases less oxygen to the tissues
    • locks hemoglobin in R-State
  33. Fetal hemoglobin
    • has high affinity of O2 than maternal Hb A
    • structure is alpha2 gamma 2
    • binds less storongly to BPG that does HBA since a serine in gamma globin replaces histidine 143 in beta globin in the central cavit binding stite of BPG
    • has only four positive charges rather than 6
    • BPG lowers affinity for oxygen
    • makes sure that you have abundant hemoglobin that binds to oxygen
  34. hemoglobinopathy
    clinical disorders resulting from a genetically determined abnormality abnormality of structure or amounts of the normal hemoglobin molecule or both
  35. chromosome 16
    two alpha and one zeta present
  36. chromosome 11
    • two gamma
    • one epsilon
    • one delta
    • one beta
  37. adult
    • more than 3 months old
    • young liver synthesizes blood
  38. globin switching
    • change in expression during development is a classic example of ordered regulation of developmental gene expression
    • embryoniic globin synthesis occurs in the yolk sac between weeks 3 - 8, but at week 5, begins to switch to the liver
    • HbF is the predominant fetal Hb and is about 70% at birth but in adulthood is only 1%
  39. Embryonic hemoglobins
    • Gower 1: zeta2epsilon2
    • Gower 2: alpha2epsilon2
    • Portland 2: zeta2gamma2
  40. Fetal Hemoglobin
    HbF: alpha2gamma2
  41. Adult hemoglobin
    HbA: alpha2beta2
  42. Gamma chains in Hb F
    • some positively charged amino acids (in the BPG binding site)
    • 2,3 BPG binds more weakly and and the O2 affinity is increased
    • facilitates transfer of O2 from the mother's HbA to the fetal HbF in the placenta
  43. sickle cell anemia
    • homozygous mutation on gene encoding the beta subunit of hemoglobin
    • results in a single amino acid substitution, valine in the place of glutamate (Glu6Val); T is substituted for A
    • a hydrophobic residuenow exists on the exterior of hemolobin, causing inappropriate association with other hemoglobin molecules in the cell
    • insoluble fibers form in the red cells causing a deformed shape
    • hemoglobin concentration in plasma is usually half of the normal concentration
  44. Hb Electrophoresis in sickle cell anemia
    • HbA moves toward anode (it being negative in charge)
    • HbS is less negative and migrates slower than HbA
    • Hb electrophoresis is a routine experiment for sickle cell trait or disease
    • at pH 8.6 nearly all human blood proteins are negatively charged
  45. sickle cell anemia symptoms
    • severe pain in the sternum and long bones where tissues become poorly oxygenated
    • hypoxia leading to dizziness, fatigue, shortness of breath
    • long term - organ failure due to ischemic necrosis (spleen)
    • management includes blood transfusions, pain, medication, hydration
    • gene therapy still being investigated
    • sickle cell trait - only one allele affected
    • Clinical features: severe hemolytic anemia punctuated by crises brought on by infection, dehydration as well as deoxygenation
  46. electrophoresis
    • proteins in a mixture are separated by electrophoresis
    • a single aa substitution in a protin can be detected
  47. Sickle cell disease = advantage in adversity
    • heterozygous individuals are less susceptible to malaria
    • shorter life span of RBC (20 days) interferes with Plasmodium species replicating
  48. hemoglobin C disease
    • produced when lysine is substituted for glutamic acid in 6th position in beta chain
    • readily forms crystals in rbc
    • life span 30-35
    • homozygous individuals show mild to moderate hemolytic anemia and splenomegaly
  49. hemoglobin SC disease
    • HbC/HbS individuals usually show only mild anemia and splenomegaly
    • individuals are prone to thrombosis and pulmonary and retinal abnormalities that lead to blindness
    • patient remains normal and asymptomatic untol some infarct - related crisis occurs (during profound hypoxic states/dehydration)
  50. hemoglobin E disease
    • GAG to AAG codon mutation on 26th position of beta globulin chain
    • heterozygous are completely asymptomatic
    • homozygotes show slight decrease in hemglobin level and rbcs may have increased fragility
    • similar mobility of HbA2 on electrophoresis - two alphas and two deltas, about 2%% of normal circulating adult hemoglobin
  51. methemoglobinnemias
    • iron Fe+3, incapable of binding to O2
    • may be acquired or inherited
    • *methemoglobin reductase deficiency
    • *glucose 6 phosphate dehydrogenase deficiency
    • may also be formed due to exposre to env. toxins
    • may also result from mutation in alpha and beta chain producing HbM
    • substitution either occurs in eiher proximal or distal histidine residues of alpha and beta chains
    • histidine for tyrosine
    • NADH - cytochrome b5 reductase converts methemoglobin to hemoglobin (deficiency leads to accumulation of methemoglobin)
  52. symptoms and treatments for methemoglobinemias
    • symptoms: cynosis and hypoxia at levels between 10-25%
    • anxiety, dyspnea, headache, at levels of 35%
    • lethal when levels reach 70%
    • treatment: asorbic acid for mild caes and methylene blue for severe cases
  53. Thalassemias
    • imbalance in synthesis of globin chains
    • most common single gene disorder in humans
    • synthesis of alpha and beta globin chains occurs in coordinated manner (alpha2beta2 HbA2)
    • either alpha or beta is defective
    • a0 or b0 thalassemias - no globlin
    • a+ or b+ thalassemias - decreased globin
  54. alpha thalassemias
    • absent or decreased
    • four copies of alpha globin genes - two each on chromosome 16
    • silent carrier - one gene defective
    • trait - two genes defective
    • HbH - three genes defective
    • Four genes defective - hydrops fetalis
    • synthesis of unaffected gamma and beta globin chains continues
    • accumulation of gamma tetramers in the newborn or beta tetramers in adults - bind with high affinity O2 is not released in tissues
  55. beta thalassemias
    • two beta globin genes one on each chromosome 11
    • beta decreased or absent
    • if one gene is defective - beta thalassemia minor (symptomless)
    • if two genes are defective - beta thalassemia major (severely anemic - Cooley's anemia and requires repeated blood transfusion)
    • physical manifestations after birth but not in utero
    • bone marrow transplantation has been more heavily considered recently
  56. collagen I
    fibrillar - skin and tendon
  57. collagen II
    fibrillar cartilage - developing cornea and viterous humor
  58. collagen III
    fibrillar - extensible connective tissue: eg. skin lung, and vascular tissue
  59. collagen IV
    network; basement membrane
  60. collagen
    • most abundant fibrous protein of the body
    • synthesized from fibroblasts, muscle cells and epithelial cells
    • primary source of structural strenght for cells and tissues
    • long rigid structure in which three polypeptides are wound around one another ina rope-like triple helix
    • dispersed as gel in viterous humor
    • bundled as tight parallel fibers in tendons
    • functions ouside the cell (initially synthesized by prepro alpha chains)
  61. collagen - struture
    • each fiber usually 1000 aa long
    • 3.3 residues per turn
    • Gly-X-Y pattern followed
    • X is often Pro
    • Y = hydroxyproline or hydroxylysine
    • right handed, but left coiled
  62. vitamin C deficiency
    impropor hydroxylation and weakening of the collagen fibers leading to scurvy
  63. lysyl oxidase
    copper containing enzyme requiring vit B6
  64. lathyrism
    • consumption of sweet pea seends
    • contains beta aminoproprionitrile which irreversibly inhibits lysyl oxidase
    • prevents tropocollagen cross linking
    • abnormalities of bones, joints, large vessels (type 1)
  65. degradation of collagen
    • collagen has long half life
    • degraded by collagenases, which are matrix metalloproteinases
    • larger fragments are further degraded by matrix proteinases
    • amino acids released enter into aa pool for reutilization
  66. Ehlers - Danlos syndrome
    • deficiency of collagen processing enzymes
    • mutations in the aa sequences of collagen types I, III, and V
    • lethal vascular malformations occur
    • fragile,loose, stretchy skin
    • abnormal joint mobility
  67. Osteogenesis imperfecta
    • brittle bone syndrome
    • bones easily bend and fracture
    • delayed wound healing
    • rotated and twisted spine leads to humped - back appearance - kyphoscoliosis
    • cause: decreased production of alpha1 and alpha2 chains or mutated forms of alpha1 and alpha2
    • mutation - replacement of glycine residues with those having bulky R groups
  68. type 1 OI - tarda
    • less severe
    • blue sclerae
  69. type 2 OI - congenita
    severe form found much later in life
  70. Menke's disease
    • kinky or steel hair disease
    • x linked, affects only male infants
    • deffect in copper binding P type ATPase (MNK) a copper transporter, in intestinal cells
    • Low serum Cu levels with deposition in intestinal cells
    • decreased function of Cu dependent lysyl oxidase
    • abnormal collagen, defective vasculature and CT
    • poor survival rate, usual fatal in infancy
    • collagen chains are on all autosomes
  71. alpha keratins
    • form tough fibers
    • found in hair nails and outer epidermal layer of mammals
    • very insoluble in water
    • structural unit: alpha helical polypeptide
    • lack alpha helix breaking aa
    • have cysteine residues that form inter - helix disulfide bridges and are therefore resistant to stretching
  72. apolar alpha edges
    interact with each other to form a super helical structure containing 2 polypeptide chains
  73. polar edge
    interacts with water on the outside of the superhelix
  74. hair formation
    2 keratin alpha chains form a coiled coil -> 2 staggered anti parallel coiled structure (protofilament) ->4 protofilaments combine to form a protofibril (H-bonds and disulfide bridges are the principal interactions between protofilament subunits) -> hundreds of filaments are packed together to form a fibril -> fibrils combine to form a fiber = hair
  75. Elastin
    • CT protein with rubber - like properties
    • found in lungs, large artery walls, elastic ligaments
    • synthesized from tropoelastin
    • aa are primarily small and nonpolar
    • tropoelastin is precursor of elastin secreted from cell to ECM and in ECM tropoelastin interacts with fibrilin
    • fibrilin allows for tropelastin is deposited
    • desmosine cross links make elastin an extensively interconnected rubbery network (elastic property)
    • inherently stable with a half - life of up to 70 years
  76. neutrophil elastase
    degrades elastin of alveolar walls and other tissue proteins
  77. alpha 1 antitrypsin
    • inhibits number of proteolytic enzymes including elastases
    • synthesized mainly in the liver and also on monocytes and alveolar macrophages
  78. alpha 1 AT deficiency
    • autosomal recessive condition
    • binding to target proteases requires a specific methionine residue in the primary structure (smoking causes this oxidation of methionine; develop severeemphysema compared to non smokers with alpha AT deficiency)
    • mutated protein polymerize in ER of hepatocytes and are not secreted
    • accumuluated polymer may result in cirrosis (scarring of the liver)
    • leads to emphysema
    • good candidate for protein replacement therapy
  79. Marfan's Syndrome
    • fibrilin is a glycoprotein which is essential for the formation of elastic fibers found in CT
    • mutations in fibrillin 1 protein are responsible
    • impaired structural integrity in: skeleton (long fingers and long bones), the eye, and cardiovascular system, esp. the aorta
  80. simple enzymes
    composed entirely of protein
  81. complex protein
    • composed of protein plus a relatively small organic/inorganic molecules
    • -coenzyme: complex organ molecule eg. NADH
    • -cofactor: small inorganic molecule eg. iron or zinc
    • -prosthetic group: cofacter/coenzyme/which is covalently attatched to protein component
    • -apoenzyme: the protein component of an enzyme
    • -holoenzyme: a complete catalytically active enzyme together with its coenzyme or metal ion
  82. with enzyme
    reactions go only one way and they are irreversible
  83. transition state
    • bent state - shape of the substrate that is least stable; if you bend it anymore it is going to break
    • enzymes bind to substrate to go through the transition state
  84. substrate
    • reactant in an enzyme/catalyse reaction
    • all enzymes have substrate binding site and sometimes called ptalisis
  85. nature of enzyme catalysis
    • enzyme provides a catalytic surface
    • surface stabilizes transition state
    • transforms transition state to product
    • recognizes and binds to substrate
  86. why is the energy required to reach transition state lower in the active site?
    stabilizes transition, expels water, reactive groups, coenzyme helps
  87. mechanism of enzyme action
    • fischer's lock and key model
    • koshland's induced fit model
  88. enzyme specificity
    • group specificity: hexose +ATP -> glucose 6 phosphate
    • absolute specificity: glucokinase: phosphorylates only glucose; galactokinase phosphorylates only galactose; arginase: hydrolyzes only arginine
  89. Trypsin
    • cuts at lysine and arginine
    • deep and negatively charged pocket
  90. Chymotrypsin
    • cuts at trypsin, phenylalanine, and tyrosine
    • non-polar pocket
  91. Elastase
    • cuts at alanine and Glycine
    • shallow and non-polar pocket
  92. mechanism of catalysis
    • acid - base catalysis - enzyme gives or takes H+ to bring about catalysis
    • substrate strain - substrate increases energy level of substrate leading to a transition state
    • covalent catalysis - covalent binding of th substrate to the enzyme due to opposite charges
  93. mode of action of enzyme
    enzymes accelerate reaction rates, but do not alter the equilibrium point of the reaction
  94. energy of activation
    • energy difference between the reactants and a high energy intermediate that occurs during the formation of product
    • high energy of activation - rates of uncatalyzed reactions are slow
    • lower energy of activation - more molecules have sufficient energy to pass through the transition state
    • enzymes lower the energy of activation and t hus allow a reaction to proceed rapidly
  95. serine proteases
    • group of enzymes which include digestive enzymes (tripsin, chymotrypsin, and elastase), several enzymes of the blood clotting cascade pancreatic lipase and acetyl cholineserase
    • enzyme prefers to adopt shape that perfectly binds the transition state - tetrahedral intermediate
  96. factors affecting enzyme activity
    • substrate concentration
    • temperature
    • pH
    • enzyme concentration
    • product concentration
    • prescence of activators or inhibitors
    • availability of coenzyme
  97. Km
    • constant and is characteristic of an enzyme and is particular substrate; measure of the affinity of the enzyme for that substrate
    • Small or low Km shows high affinity
    • Large or high Km shows low affinity
  98. km =
    1/2 vmax
  99. competitive inhibition
    • has a structure similar to substrate
    • occupies active site
    • competes with substrate for active site
    • inhibition is reversed by increasing substrate concentration
    • vmax is unchanged
    • km is increased
  100. methanol poisoning
    • methanol poisoning causes decrease blood pressure and bdy temperature and an increase in respiratory rate
    • ethanol acts as a competitive inhibitor
    • "wood" alcohol and antifreeze contain high methanol concentrations
  101. noncompetitive inhibition
    • not a structural analogue
    • binds to the enzyme but not at active site
    • chages the shape of enzyme
    • substrate binds but diminished catalysis occurs in the presence of inhibitor
    • effect is not reversed by adding substrate
    • KM is unaltered
    • vmax is decreased proportionally to inhibitor concentration
  102. uncompetitive inhibitors
    • inhibit mainly multisubstrate enzymes
    • inhibitor binds only after first substrate fors ES complex
    • ESI complex cannot form products
    • km and vmax are both changed
  103. irreversible inhibition
    • inhibitor binds covalently with the enzyme to form a stable complex
    • it is not a structural analogue, it binds to site other than active site
  104. transition state analogs
    • active site of an enyme is complementary to the substrate transition state
    • stable molecules designed to resemble the transition state
    • bind to an enzyme with more affinity than the substrate
    • pharmaceutical agents can be designed using transition state analogs to inhibit specific enzymatic reactions (non covalent)
  105. long term regulation of enzyme activity
    • regulation of gene expression
    • regulated enzyme degradation can be slowed down or speeded up by ubiquitin/proteosome pathway and lysosomal pathway
  106. short term regulation of enzyme activity
    • does not affect the concentration of enzyme
    • reversible and rapid in action and actually carries out most of the moment - to - moment physiologcial regulation of enzyme activity
    • include:
    • -product inhibition, feedback inhibition, activation of pre-existing pools of inactive pro-enzymes to produce active enzymes
    • -regulation by reversible covalent modificatin, allosteric regulation
  107. pro-enzyme activation
    • aka zymogens
    • generally synthesized in abundance stored in secretory granules and covalently activated upon the release form their storage sites
    • rapid method of increasing enzyme activity
    • irreversible process
    • clotting factors
  108. regulation by covalent modification
    major mechanism for rapid and transient regulation of enzyme activity through phosphorylation or dephosphorylation
  109. phosphorylation can be reversed by a separate class of enzymes
    known as phosphoprotein phosphatases
  110. allosteric regulation
    • "oligomers, at least 2 domains, often more
    • effectors = modulator
  111. allosteric site
    is one which is distinct from the active site
  112. allosteric modulators
    influence enzyme activity
  113. positive modulator
    activator site
  114. negative modulator
    inhibitory site
  115. allosteric regulation of enzymes
    • some multimeric enzymes bind small, physiologically important molecules that modulate their activity
    • these are known as allosteric enzymes and the small regulatory molecues to which they bind are known as allosteric effectors
    • the hallmark of effectors is that when they bind to enzymes they alter the catalytic properties of an enzyme's active site
  116. heterotropic effectors
    • not identical to the substrate
    • these effectors can range from simple inorganic molecules to complex nucleotides such as cyclic adenosine monophosphate (cAMP)
  117. Homotrophic effectors
    • when the substrate itself serves as an effector, the effect is said to be homotropic usually a positive effector
    • Michaelis - Menten curve is sigmoidal rather than hyperbolic - the effect being due to cooperativeity
  118. isoenzymes
    • different forms of the same enzyme, catalyzing same chemical reactions but preent at different tissues exhibiting different physcial and kinetic properties
    • coded by different genes at different tissues
    • useful in clincal diagnosis and monitoring
  119. LDH1
    myocardial infarction
  120. LDH5
    • hepatitis
    • liver disease, muscle injury
  121. CK2
    myocardial infarction
  122. enzymes as therapeutic agents
    have been used in myocardial infarction by activating plasminogen to plasmin and helping in dissolving blood clots
  123. nucleotides
    • carbon ring structures containing nitrogen linked to a 5 - carbon sugar (ribose) and phosphate
    • monomer units or building blocks of nucleic acids
    • act as intracellular source of energy
    • form a part of many coenzymes
    • donors: of phosphoryl groups
    • some involved in signal transduction
    • act as proton donors or acceptors in hydrogen bonds
    • purine analog allopurinol, used in treatment of hyperuricemia and gout
  124. purines
    A and G
  125. Pyrimindines
    C and T
  126. nucleosides
    • purine and pyrimidine bases with sugar linked to a ring nitrogen
    • nucleotides are nucleosides with a phosphoryl group esterfied to a hydroxyl group of the sugar
  127. nucleic acids
    • bases attach to the C-1 of ribose or deoxyribose
    • pyrimidines attach to the pentose through the N-1 position
    • purines attatch to the pentose trhorough the N-0 position
  128. polynucleotides
    • sequence of side chains (bases determine the gene product
    • nucleic acid structure depends on sequence of bases and on the type of pentose sugar
    • hydrogen bonding interactions are especially important in nucleic acids
  129. structure of DNA
    • two helical chains wound around the axis in a right - handed fashion
    • two strands run in an anti-parallel fashion
    • deoxyribose and phosphate groups forms the backbone of the helix
    • planar purine and pyrimidine bases of both strands are stacked inside the helix
    • types of DNA: A,B, and Z
  130. B form DNA
    • 10.5 base pairs per turn
    • distance between base pairs is 3.4 A
    • distance per turn is 36 A
    • width of B DNA is 20 A
Card Set
Block 1