Biochemistry Cheat Sheet

BIOCHEMISTRY! generally! deals! with! the! physical! and! chemical! properties! of! compounds! that! that! make! up! the! smallest!unit!of!life!and!how!these!compounds!undergo!processes!and!relate!it!with!how!it!affects!the!daily!function!of! human!beings.!! ! I.! 8! 8! 8! 8! 8! AMINO/ACIDS/ / These! are! organic! carboxylic! acids! that! has! at! least! one! amino! group! replacing! a! hydrogen! atom! of! the! hydrocarbon!chain.!! All!of!the!20!amino!acids,!with!the!exception!of!Glycine,!are!levorotatory!since!glycine!doesn’t!have!an!asymmetric! carbon,!hence!it!cannot!exhibit!stereoisomerism.!! Sulfur!containing! o! Cysteine!and!Methionine! Glycine! o! Acts!as!an!inhibitory!neurotransmitter;!antagonized!by!strychnine! In!a!protein!chain,!the!α!8!carboxyl!group!of!each!amino!acid!is!joined!by!peptide!bonds!covalently!to!the!α!8!amino! group!of!the!next!amino!acid! ! NAME/ 3/LETTER/ 1/LETTER/ CLASSIFICATION/ STRUCTURE/ SYMBOL/ SYMBOL/ Alanine! Ala! A! Aliphatic! ! (Hydrophobic!Side! Chain)! Isoleucine! Ile! I! Aliphatic! (Hydrophobic!Side! Chain)! Leucine! Leu! L! Aliphatic! ! (Hydrophobic!Side! Chain)! Methionine! Met! M! Aliphatic! (Hydrophobic!Side! Chain)! Valine! Val! V! Aliphatic! (Hydrophobic!Side! Chain)! Phenylalanine! Phe! F! Aromatic! (Hydrophobic!Side! Chain)! Tryptophan! Trp! W! Aromatic! (Hydrophobic!Side! Chain)! ! ! ! ! ! Tyrosine! Tyr! Y! Aromatic! (Hydrophobic!Side! Chain)! ! Asparagine! Asn! N! Polar!Neutral!Side! Chain! Cysteine! Cys! C! Polar!Neutral!Side! Chain! Glutamine! Gln! Q! Polar!Neutral!Side! Chain! Serine! Ser! S! Polar!Neutral!Side! Chain! Threonine! Thr! T! Polar!Neutral!Side! Chain! Aspartic!Acid! Asp! D! Acidic! Glutamic!Acid! Glu! E! Acidic! Arginine! Arg! R! Basic! Histidine! His! H! Basic! Lysine! Lys! K! Basic! Glycine! Gly! G! Unique! Proline! Pro! P! Unique! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! II.! PROTEINS/ ! 8! 8! The!major!cell!components!that!play!a!big!role!in!all!biological!processes! These! are! organic! compounds! with! high! –! molecular! weights! that! contain! nitrogen! with! complex! structural! organization! 8! Contain!amino!acids!linked!by!covalent!peptide!bonds! 8! Amphoteric!in!nature! ! A.! Protein/Structures/ 8! Structurally! organized! into! four! levels! (with! each! level! having! its! proper! specificity):! PRIMARY,! SECONDARY,! TERTIARY,!and!QUATERNARY!! ! 1.! Primary/Structure/ / o! The!simplest!level!of!structural!organization!composed!of!the!amino!acid!resides!linked!through!peptide! bonds! o! The!sequence!is!written!from!left!to!right!(N8!Terminal!to!C!–!Terminal!amino!acid)! o! In!an!electric!field:!Positively!charged!proteins!8>!Cathode!(8)!;!Negatively!charged!proteins!8>!Anode!(+)!;! Proteins!at!the!isoelectric!pH!8>!no!migration!since!net!charge!is!0! ! 2.! Secondary/Structure/ ! 8! o! α!8!Helix! !! A!helical!configuration!of!the!polypeptide!chain!formed!by!the!Hydrogen!bonding!between!the! peptide!groups!of!every!first!and!fourth!AA!residues.! ! o! β!8!Sheets! !! Pleated!sheet!structure!resembling!an!accordion! !! Can!be!in!a!form!of!a!parallel!or!an!antiparallel!chain! !! Examples!are!Keratin,!Collagen,!and!Fibroin! !! Creutzfeldt!–!Jakob!Disease! ¥! Caused!by!the!transmission!of!Prions!(a!proteinaceous!infectious!agent!that!causes! neurodegenerative!diseases)!that!results!to!the!misfolding!of!the!normal!prion!protein! found!abundantly!in!the!brain! o! Prions!causes!Mad!Cow!Disease! ¥! Replacement!of!the!normal!α!8!helical!arrangement!of!the!normal!prion!protein!with!β!8! pleated!sheet! ¥! Dementia!and!Involuntary!Jerking!Movements!(Startle!Myoclonus)! ! 3.! Tertiary/Structure/ / o! Refers!to!the!spatial!arrangement!of!the!polypeptide!chain! o! Can!either!be!Fibrous!or!Globular! o! Different!bonds!contribute!to!the!stabilization!of!the!structure! !! Covalent!bond:!Disulfide!Bond! !! Polar!bonds:!Hydrogen!bonding,!Ionic!bonding! !! Non8Polar/!van8der8Waals! o! Chaperones! !! Proteins!that!assist!in!the!folding!and!unfolding!of!the!polypeptide!to!correctly!form!the!tertiary! structure! !! Example:!Heat!Shock!Proteins! ! 4.! Quaternary/Structure/ ! o! Spatial!arrangement!of!proteins!made!up!of!several!polypeptide!chains,!with!each!peptide!chain!having! a!tertiary!structure! o! Referred!to!as!Oligomers! o! Example:!Hemoglobin! ! ! Denaturation/(Denativation)!of!proteins!happen!when!certain!agents!such!as!heat!and!urea!destroy!the!higher! 8! ! ! ! ! ! ! structural!levels!of!protein!without!destroying!the!peptide!bonds! Renaturation/(Renativation),!on!the!other!hand,!is!the!recovery!of!the!protein!from!its!denatured!state!! ! B.! Medically/Important/Proteins/ / 1.! Hemoglobin/ o! Globular!Transport!Protein!for!Oxygen/ o! Contains!Heme!which!is!a!complex!of!porphyrin!ring!and!a!Ferrous/ o! Sickle!Cell!Anemia/ !! Caused!by!a!mutation!in!hemoglobin!where!the!Glutamate!at!position!six!in!the!beta!–!chain!of! hemoglobin!is!replaced!by!Valine/ o! Has!higher!affinity!to!CO!than!CO2/ / 2.! Collagen/ o! Found!mainly!in!the!bones!and!cartilage! o! Mainly!contains!Glycine,!Proline,!Hydroxyproline! o! Types:! !! I!–!Found!in!skin!and!bones! ¥! Osteogenesis/Imperfecta!is!a!disorder!in!the!synthesis!of!Type!I!collagen!characterized! by!a!distinctive!blue!sclera!and!predisposed!multiple!childhood!fracture/ !! II!–!Found!in!the!Cartilage! !! III!–!Found!in!the!arterial!walls! !! IV!–!found!in!the!basal!lamina! !! V!–!Found!in!the!hair!and!placenta! o! Ehlers!–!Danlos!Syndrome! !! A!group!of!connective!tissue!disorders!that!are!generally!characterized!by!hyperextensible!skin,! joint!hypermobility,!and!defects!in!large!blood!vessels! ! 3.! Insulin! o! A!polypeptide!hormone!produced!by!the!beta!–!cells!of!the!pancreas! o! Synthesis!of!Preproinsulin!in!the!rough!ER!8>!Proinsulin!is!cleaved!in!the!secretory!granules!8>!C!–!petide! is!released!8>!the!remaining!molecule!forms!Insulin! ! C.! Qualitative/Tests/for/Proteins/&/Amino/Acids! ! 1.! Biuret!Test! o! Identifies!the!presence!of!proteins! o! Uses!1%!NaOH!and!a!solution!of!Copper(II)!sulfate! o! Positive!Result:!Violet!Color! ! 2.! Ninhydrin!Test! o! Uses!Ninhydrin!to!detect!the!presence!of!amines! o! Positive!Result:!Purple!(Ruhemann’s!Purple)!=!Amino!Acids!with!a!free!amino!group,!Yellow!=!Imino! Acids!(Proline!&!Hydroxyproline)! ! 3.! Xanthoproteic!Test! o! For!Tyrosine,!Tyrptophan! o! Uses!conc.!HNO3!and!40%!NaOH! o! Positive!Result:!Yellow!Color! ! 4.! Millon’s!test! o! Specific!for!Tyrosine! o! Uses!Mercury!dissolved!in!conc.!HNO3! o! Positive!Result:!Yellow!Coloration! ! 5.! Hopkins’s!–!Cole!Test! o! Specific!for!Tyrosine!(indole!group)! o! Uses!Glyoxylic!Acid!in!Glacial!Acetic!Acid!and!Sulfuric!Acid! o! Positive!Result:!Purple!Color!on!the!surface! ! 6.! Nitroprusside!Test! o! Specific!for!Cysteine! o! Uses!nitroprusside!in!alkaline!solution! o! Positive!Result:!Red!Coloration! ! 7.! Sakaguchi!Test! o! Specific!for!Arginine!(guanido!group)! o! Uses!NaOH,!α!8!naphthol,!and!Bromine!solution! ! ! ! ! III.! 8! ENZYMES/ / These!are!biological!catalysts!of!protein!nature!which!catalyzes!energetically!feasible!reaction!without!altering!the! reaction!route.!Like!other!nonbiological!catalysts,!enzymes!are!not!consumed!during!a!reaction!and!decreases!the! Ea!of!a!reaction.! ! 8! Enzymes!are!highly!specific!for!their!substrates!and!products!with!most!enzymes!recognizing!only!1!compound! as!substrate.!! 8! The!velocity!of!a!reaction!is!directly!proportional!with!temperature!at!an!optimal!pH! o! However,!as!the!temperature!goes!higher!than!37!degrees!(Celsius),!enzymes!start!to!degrade! o! !Changes!in!pH!can!cause!changes!in!reaction!and!may!cause!enzymes!to!denature! !! Pepsin:!optimal!pH!is!2! ! Many!enzymes!require!cofactors!or!coenzymes!to!catalyze!reactions.!These!coenzymes!are!commonly!derived! from!vitamins!and!metal!ions.! ! 8! ! A.! Nomenclature/ / 1.! Oxidoreductases! o! Catalyzes!REDOX!reactions! o! Also!called!as!dehydrogenases!or!reductases! 2.! Transferases! o! Catalyzes!reactions!involving!the!transfer!of!different!groups!from!the!substrate!to!another! o! Amino!Transferases,!Methyl!Transferases! 3.! Hydrolases! o! Catalyzes!the!substrate!bond!cleavage!by!adding!water! o! Amylase,!Saccharase! 4.! Lyases! o! Catalyze!bond!–!cleaving!reactions!without!oxidation!or!addition!of!water! o! Pyruvate!decarboxylase! 5.! Isomerases! o! Catalyzes!structural!rearrangements! o! Triose!Isomerase! 6.! Ligases! o! Also!called!as!synthetases! o! Catalyzes!the!addition!of!2!moleculesusing!ATP!as!energy!source! o! DNA!–!Ligase! ! B.! Inhibition/ 8! Inhibitors!are!agents!capable!of!exerting!a!specific!deterrent!action!on!the!activity!of!en!enzyme/ / 1.! Competitive! o! An!inhibitor!that!is!structurally!related!to!the!substrate!binds!to!the!active!center!preventing!the! formation!of!the!enzyme!–!substrate!complex! 2.! Noncompetitive! o! An!inhibitor!binds!to!the!enzyme!or!enzyme!–!substrate!complex!which!leaves!the!active!center!free!and! may!induce!conformational!change!which!hinders!the!formation!of!the!enzyme!–!substrate!complex.!! 3.! Irreversible/ o! An!inactivator!binds!covalently!to!the!enzyme!and!inactivates!it.!/ / C.! Isoenzymes/ / 8! Also!known!as!isozymes! 8! These!are!enzymes!that!may!differ!in!amino!acid!sequences!and!physical!properties!but!catalyze!the!same! reaction! ! ! IV.! / DNA/&/RNA/ A.! 8! 8! 8! DNA/Structure/ Contains!nucleotides!that!is!made!up!of!a!nitrogenous!base,!deoxyribose,!and!phosphate! The!nitrogenous!bases!are!classified!into!Purines!and!Pyrimidines! The!primary!structure!of!DNA!and!RNA!is!a!linear!polynucleotide!chain!made!up!of!mononucleotides!which!are! linked!by!a!3’,5’!–!phosphodiester!bond!(3’!–!C!of!one!sugar!to!the!5’!–!C!of!the!next!sugar)! ! / / / / / / / / / / / / / B.! DNA/Double/Helix/ 8! Proposed!by!Watson!and!Crick!in!1953/ 8! The!secondary!structure!of!DNA!is!formed!by!the!pairing!two!polynucleotide!chains!that!are!antiparallel./ o! One!chain!runs!5’!–!3’!and!the!other!3’!–!5’/ o! The!base!sequences!of!the!two!strands!are!complementary/ !! Adenine!and!Thymine!via!2!hydrogen!bonds!(major!groove)/ !! Guanine!and!Cytosine!via!3!hydrogen!bonds!(minor!groove)/ 8! One!full!turn!of!the!DNA!helix!contains!10!nucleotides.! 8! Has!3!different!conformations:! o! B!Form:!Right!Handed! o! Z!Form:!Left!Handed! o! A!Form:!Dehydrated!and!compact;!Right!Handed! ! C.! Denaturation/ 8! Separation!of!the!DNA!strands!due!to!heat!or!alkali!exposure!without!breaking!the!phosphodiester!bond/ / D.! Renaturation/ 8! Upon!heating,!DNA!strands!separate!and!the!base!pairs!reform!once!the!temperature!is!slowly!decreased!! ! E.! Hybridization/ 8! A!single!strand!of!DNA!or!RNA!pairs!with!a!complementary!base!sequence!on!another!strand!of!DNA!or!RNA! ! F.! Histones/ 8! These!are!small,!basic!proteins!rich!in!Arg!and!Lys;!not!present!in!prokaryotes! 8! Eukaryotic!chromatins!consist!of!a!DNA!complexed!with!histones! ! G.! RNA/vs./DNA! 8! RNA!contains!ribose!as!sugar!instead!of!deoxyribose! 8! Uracil!replaces!Thymine!! ! Single!stranded!with!extensive!base!pairing! RNAs!can!sometimes!act!as!catalysts!and!enzymes!(ribonucleases,!Peptidyl!transferase)! ! H.! Types/of/RNA/ 8! 8! / 1.! Messenger!(mRNA)! o! Contains!a!cap!consisting!of!a!methylated!guanine!triphosphate!attached!to!the!hydroxyl!group!on!the! ribose!at!the!5’!end! o! The!poly(A)!tail!contains!up!to!200!Adenine!nucleotides! ! 2.! Ribosomal!(rRNA)! o! Aids!in!the!formation!of!ribosomes! o! Prokaryotic:!70S!(Large!subunit!=!50S!;!Small!subunit!=!30S)! o! Eukaryotic:!80S!(Large!subunit!=!60S!;!Small!subunit!=!40S)! ! 3.! Transfer!(tRNA)! o! Has!a!characteristic!cloverleaf!structure! ! ! ! ! V.! DNA/REPLICATION! ! 8! Known!as!the!transfer!of!genetic!information!within!a!single!class!of!nucleic!acids,!i.e.!from!DNA!to!DNA!or,!as!in! certain!viruses,!from!RNA!to!RNA.!! 8! DNA!Replication!is:! o! Bidirectional! !! Replication!begins!at!a!specific!origin!and!simultaneously!moves!out!in!both!directions! !! Prokaryotes!have!one!site!of!origin!while!eukaryotes!can!have!multiple!sites!of!origin! ! o! Semiconservative! !! The!resulting!daughter!DNA!contains!one!intact!parental!strand!and!one!newly!synthesized! complementary!strand! ! A.! Steps/in/Replication/ / 1.! Initiation! a.! The!parental!DNA!is!separated!and!uncoiled!by!helicases!where!the!uncoiled!DNA!strand!serves!as!the! template! b.! As!the!strands!separate,!an!active!site!for!synthesis!known!as!replication!fork!is!formed!where!each! separated!strand!is!stabilized!by!a!single!–!stranded!binding!protein! c.! As!the!strands!separate,!supercoiling!happens!which!is!removed!by!DNA!Topoisomerase! !! Etoposide!inhibits!topoisomerase! d.! The!Primase!aids!in!the!production!of!the!RNA!primer!in!a!5’!–!3’!direction!! ! 2.! Elongation!&!Termination! a.! From!the!initiation!site,!DNA!Polymerase!III!adds!deoxyribonucleotides!at!the!3’!OH!end!of!the! primer! !! DNA!polymerase!can!only!copy!in!a!3’!–!5’!direction!and!produce!the!daughter!strand!in!a!5’!–!3’! direction! !! DNA!polymerase!always!requires!primers!and!cannot!initiate!the!formation!of!new!strands! b.! DNA!Polymerase!III!forms!continuous!strands!in!a!3’!–!5’!direction!forming!the!leading!strand! c.! In!the!5’!–!3’!strand,!a!discontinuous!formation!of!DNA!happens!forming!smaller!fragments!known! as!Okazaki!fragments.!These!fragments!are!joined!together!by!DNA!ligase! d.! Once!complete,!RNA!primer!is!removed!by!the!exonuclease!acivity!of!DNA!Pol!I!! e.! Gaps!are!filled!with!the!complementary!bases! f.! Replication!is!terminated,!forming!2!daughter!DNA!molecules.! ! VI.! 8! 8! 8! 8! 8! RNA/TRANSCRIPTION/ / The!process!of!making!an!RNA!from!a!DNA!template!is!known!as!transcription.! It!is!the!major!control!point!in!gene!expression!and!protein!production.!! Catalyzed!by!DNA!–!dependent!RNA!polymerase! No!primer!is!needed! Uses!one!strand!of!DNA!as!template! A.! 8! 8! 8! RNA/Polymerase/ Can!initiate!synthesis!of!new!chains!without!a!primer! Copies!the!DNA!template!in!a!3’!–!5’!direction!and!the!resulting!RNA!elongates!in!a!5’!–!3’!!direction! Precursors:!Ribonucleoside!Triphosphates!(ATP,!UTP,!GTP,!and!CTP)! / ! B.! Steps/in/Prokaryotic/Transcription! / 1.! Initiation!and!Elongation! ! o! Rifampin!inhibits!the!beta!subunit!of!Bacterial!dependent!RNA!Polymerase! o! Actinomycin!D!binds!to!DNA!and!inhibits!the!elongation!of!RNA!Transcription!by!RNA!Polymerase! ! a.! RNA!polymerase!is!directed!by!the!sigma!factor!to!bind!to!the!promoter!! o! Promoters!contain!a!sequence!TATAAT!known!as!the!Pribnow!box!or!TATA!BOX! o! In!eukaryotes,!Hogness!box!(TATA!Box)!has!a!sequence!of!TATATAA! b.! An!RNA!Polymerase!–!closed!promoter!complex!is!formed! c.! d.! e.! f.! ! ! ! ! The!DNA!unwinds!at!promoter!and!forms!the!open!promoter!complex! RNA!polymerase!initiates!the!mRNA!synthesis!with!a!purine!ribonucleoside!triphosphate! RNA!polymerase!holoenzyme!catalyzes!the!elongation!of!mRNA!by!about!4!more!units! Upon!reaching!about!10!nucleotides,!the!sigma!–!subunit!dissociates!and!will!bind!to!another!RNA!Polymerase! ! 2.! Termination! ! a.! Intrinsic!(Rho!–!independent!Transcription!Termination)! o! Controlled!by!specific!sequences!called!termination!sites!wherein!the!sequences!form!a!hairpin!loop! structure!that!allows!the!RNA!Polymerase!to!detach!from!the!DNA!template!strand! ! b.! Rho!–!dependent!Transcription!Termination! o! Involves!the!Rho!–!Protein! o! The!rho!–!protein!binds!to!the!RNA!and!chases!the!polymerase!until!it!reaches!the!termination!site!to! facilitate!the!dissociation!of!the!RNA!Polymerase!from!the!DNA!Template!Strand.! / C.! Eukaryotic/Transcription! / 1.! RNA!Polymerases!(Promoters)! a.! RNA!Pol!I!! !! Found!in!the!nucleoulus!and!synthesizes!the!precursors!of!ribosomal!RNA! b.! RNA!Pol!II! !! Found!in!the!nucleoplasm!and!synthesizes!mRNA!precursors! !! α!8!Amanitin!(a!toxin!from!the!mushroom!Amanita'phalloides)!binds!and!inhibits!RNA!Pol!II! which!halts!mRNA!synthesis!resulting!to!severe!GIT!symptoms,!liver!toxicity,!and!death.!! c.! RNA!Pol!III! !! Found!in!the!nucleoplasm!and!synthesizes!the!tRNA!precursors! ! 2.! Steps/in/Eukaryotic/Transcription/ / a.! mRNA!Synthesis/ 1.! RNA!Polymerase!II!produces!a!heterogenous!nuclear!RNA!(hRnNA)!containing!exons!and!introns/ !! Exons!are!sequences!appearing!in!the!mature!mRNA/ !! Introns!are!the!non8coding!region!and!are!removed!during!splicing/ 2.! The!primary!transcript!(hnRNA)!is!capped!at!the!5’!end/ 3.! A!poly(A)!tail!with!a!nucleotide!length!range!of!20!–!200!!is!added!at!the!3’!end!of!the!transcript/ 4.! The!introns!are!removed!and!the!exons!are!connected!to!form!the!mature!mRNA!through!splicing/ / 3.! Reverse/Transcription/ o! The!process!of!transcribing!the!single!stranded!RNA!into!a!double!–!stranded!DNA!! o! Enzyme:!Reverse!Transcriptase!(RNA!–!dependent!DNA!polymerase)!! o! Retroviruses!contain!RNA!as!genetic!material! / VII.! RNA/TRANSLATION/AND/PROTEIN/SYNTHESIS/ / A.! Genetic/Code/ 8! A!collection!of!codons!that!specify!all!the!amino!acids!found!in!proteins! 8! Characteristics:! o! It!is!degenerate!(Redundant;!Many!amino!acods!have!numerous!codons)! o! It!is!non!–!overlapping! !! Begins!with!the!start!codon!AUG!(Methionine)!near!the!5’!end!of!the!mRNA!which!determines! the!reading!frame! !! Ends!with!a!stop!codon!(UGA,!UAA,!UAG)!near!the!3’!end! o! The!code!is!commaless!(no!markers!to!differentiate!one!codon!from!one!another)! o! The!code!is!nearly!universal! 8! Codons! o! A!sequence!of!3!bases!in!mRNA!that!specifies!a!particular!Amino!Acid! ! B.! Mutations! 8! Mutations!in!DNA!are!carried!over!into!the!mRNA!that!causes!changes!in!the!encoded!protein! ! 1.! Point!Mutations! o! A!base!in!the!DNA!is!replaced!by!another!which!alters!the!codon!in!the!mRNA! ! a.! Silent! o! The!codon!containing!the!changed!base!codes!for!the!same!amino!acid! b.! Missense! o! The!codon!containing!the!changed!base!codes!for!a!different!amino!acid! c.! Nonsense! o! The!codon!containing!the!changed!base!codes!for!a!stop!codon! ! ! ! ! 2.! Insertions! o! Occur!when!a!base!or!a!number!of!bases!are!added!to!the!DNA! ! 3.! Deletions! o! Occur!when!a!base!or!a!number!of!bases!are!added!to!the!DNA! ! 4.! Frameshift! o! Occurs!when!the!number!of!bases!added!or!deleted!is!not!a!multiple!of!3!which!shifts!the!reading!frame! to!a!completely!different!set!of!codons! ! C.! Steps/in/Eukaryotic/Translation/ / 1.! Initiation! ! a.! The!40S!ribosomal!subunit!binds!close!to!the!5’!cap!until!it!recognizes!the!start!codon!(AUG).! !! The!ribosome!recognizes!the!AUG!in!the!correct!context!known!as!the!Kozak!Sequence! (ACCAUGG)! !! In!prokaryotes,!Streptomycin!binds!to!the!30S!subunit!which!hinders!initiation! b.! A!special!initiator!tRNA!recognizes!the!start!codon!carries!a!non!formylated!Methionine! c.! The!60S!ribosomal!unit!is!recruited!to!form!the!80S!initiation!complex.!! ! 2.! Elongation! ! a.! The!ribosome!moves!from!5’!to!3’!direction! b.! The!amino!acid!containing!tRNA!(aminoacyl8tRNA’s)!forms!a!complex!with!an!elongation!factor!and! enters!the!empty!A!8!site! c.! The!anticodon!of!the!aminoacyl8tRNA!is!matched!against!the!mRNA!codon!in!the!A!8!Site! d.! When!the!correct!aminoacyl8tRNA!enters!the!A8Site,!the!polypeptide!chain!in!the!P!8!site!is!linked!to! the!new!amino!acid!in!the!A!–!Site!via!a!peptide!bond! !! The!reaction!is!catalyzed!by!peptidyltransferase! ¥! Chloramphenicol!inhibits!prokaryotic!peptidyltransferase! !! The!new!peptidyl8tRNA!is!left!in!the!A!site! e.! The!peptidyl8tRNA!is!translocated!from!the!A!–!Site!to!the!P!–!Site!facilitated!by!an!elongation!factor.! !! Eryhtromycin!binds!to!a!site!on!the!50S!subunit!which!inhibits!translocation! f.! A!new!aminoacyl!–!tRNA!in!the!A!–!Site!is!made!available!for!the!next!codon!in!the!mRNA! g.! The!steps!are!repeated!until!the!ribosome!encounters!a!stop!codon.! ! 3.! Termination! ! a.! The!stop!codon!is!recognized!by!a!release!factor.! b.! The!newly!synthesized!protein!is!released!and!the!synthesizing!complex!dissociates.!! ! VIII.! CARBOHYDRATES/ ! 8! 8! 8! 8! 8! The!most!widespread!compounds!involved!in!the!buildup!and!biological!functions!of!the!cell! Presence!of!a!carbonyl!(Aldo!or!Keto!group)!and!at!least!two!hydroxyl!groups.! Stereoisomers:!Same!chemical!formula!but!differs!in!the!position!of!hydroxyl!groups! Enantiomers:!Stereoisomers!that!are!mirror!images! Epimers:!Stereoisomers!that!differ!in!the!position!of!the!hydroxyl!group!at!only!one!asymmetric!carbon.!! ! A.! Monosaccharides/ 8! These!are!simple!carbohydrates!that!are!named!depending!on!the!number!of!Carbon!atoms!and!the!specific! carbonyl!group!present.!! 8! They!can!either!be!Dextrorotatory!or!Levorotatory!! 8! Examples;!D!–!Galactose,!L!–!Fructose! ! B.! Oligosaccharides! 8! Composed!of!2!to!12!monosaccharide!units!linked!by!a!glycosidic!bond! 8! Sucrose! o! Table!Sugar! 8! o! Glucose!+!fructose! Lactose! o! Milk!Sugar! o! Galactose!–!linked!β81,4!to!glucose! ! ! ! ! C.! Polysaccharides! 8! These!are!high!–!molecular!carbohydrates!with!more!than!ten!monosaccharide!units!linked!by!glycosidic!bonds! 8! Neutral!Polysaccharides!such!as!Starch!(Plants)!and!Glycogen!(Human!and!Animals)!are!found!inside!the!cell!as! reserve!material! 8! Acidic!polysaccharides!such!as!Chondroitin!sulfate!and!Hyaluronic!acid!are!found!extracellularly! ! ! D.! Digestion/of/Carbohydrates! 8! Salivary!α!8!amylase,!which!is!present!in!the!saliva,!!cleaves!starch!by!breaking!the!α!8!1,4!linkage!between! glucose!residues! 8! Sucrase!converts!sucrose!to!glucose!and!fructose! 8! Lactase!converts!lactose!to!glucose!and!galactose! 8! α!8!glucosidase!inhibitors!work!in!the!intestine!to!slow!down!the!digestion!of!carbohydrates!to!facilitate!better! postdigestive!blood!glucose!control! ! E.! Qualitative/Tests/for/Carbohydrates/ / 1.! Molisch!Test! o! General!test!for!Carbohydrates! o! Monosaccharides!give!the!most!rapid!result! o! Uses!α!8!naphthol!&!sulfuric!acid! o! Positive!Result:!purple!ring! ! 2.! Benedict’s!Test! o! Test!for!the!presence!of!reducing!sugars! !! All!monosaccharides!give!a!positive!result! o! Uses!Copper(II)!sulfate,!Sodium!citrate!and!Sodium!carbonate!in!a!mildly!basic!solution! o! Positive!Result:!red!precipitate! ! 3.! Barfoed’s!Test! o! Uses!Copper(II)!in!a!slightly!acidic!medium! o! Used!to!differentiate!a!reducing!monosaccharide!from!a!reducing!disaccharide! o! Positive!Result:!red!precipitate!(within!3!minutes!=!Monosaccharide,!longer!than!3!minutes!=! disaccharide)! ! 4.! Bial’s!Test! o! Test!for!differentiating!pentose!and!hexose!monosaccharides! o! Uses!conc.!HCl!and!orcinol!+!Ferric!Chloride! o! Positive!Result:!Pentoses!=!Bluish!to!green,!Hexoses!=!Brownish!to!gray! ! ! 5.! Seliwanoff’s!Test! o! Test!for!differentiating!aldoses!from!ketoses! o! Uses!6M!HCl!and!resorcinol!! o! Positive!Result:!Ketoses!=!Cherry!Red,!Aldoses!=!Bluish!8!green!to!peach! ! IX.! 8! 8! 8! A.! 1.! 2.! 3.! GLYCOLYSIS! ! Principal!route!of!metabolism!for!glucose! Takes!place!in!the!cytoplasm;!Can!provide!ATP!anaerobically! Glucose!enters!the!cells!via!a!transport!protein!(GLUTs)! ! Steps/in/Glycolysis! ! Glucose!8>!glucose!6!–!phosphate! o! Utilizes!ATP!and!produces!ADP! o! Catalyzed!by!hexokinase!in!all!tissues;!glucokinase!in!the!liver! o! Hexokinase!is!inhibited!by!Glucose868Phophate!making!it!active!when!G6P!is!depleted! o! Glucokinase!is!induced!when!insulin!levels!are!high! Glucose!6!–!phosphate!is!isomerized!to!Fructose!6!–!phosphate!byPhosphoglucose!isomerase! Fructose!6!–!phosphate!is!phosphorylated!by!ATP!to!form!Fructose!1,6!–!Biphosphate!and!ADP! o! Catalyzed!by!Phosphofructokinase81!(PFK81)! o! The!first!committed!step!of!glycolysis!(Irreversible)! 4.! Fructose!1,6!–!Biphasphate!is!cleaved!by!aldolase!to!form!triose!phosphates,!Glyceraldehyde!38phosphate!(G3P)! and!Dihydroxyacetone!phosphate!(DHAP)! 5.! DHAP!is!isomerized!by!Triose!phosphate!isomerase!(TPI)!to!G3P! o! 2!moles!of!G3P!are!formed!for!every!mole!of!Glucose! o! Deficiency!from!TPI!causes!neonatal!onset!hemolytic!anemia!and!progressive!neurologic!involvement! 6.! G3P!is!oxidized!by!NAD+!and!reacts!with!inorganic!phosphate!to!form!1,38biphosphoglycerat!and!NADH! 7.! 1,38Biphosphoglycerate!reacts!with!ADP!to!produce!3!–!Phosphoglycerate! o! Catalyzed!by!Phosphoglycerate!kinase! 8.! 3!–!Phosphoglycerate!8>!2!–!Phosphoglycerate! o! Catalyzed!by!Phosphoglyceromutase! 9.! 2!–!Phosphoglycerate!Is!dehydrated!by!enolase!to!form!PEP! 10.! Phosphoenolpyruvate!reacts!with!ADp!8>!Pyruvate!+!ATP! o! Catalyzed!by!Pyruvate!Kinase!(more!active!in!fed!state)! o! Lactate!dehydrogenase!converts!pyruvate!to!Lactate! o! Puyruvate!carboxylase!converts!pyruvate!to!Oxaloacetate! o! Transamination!of!Pyruvate!forms!Alanine! ! B.! Shuttles! 1.! Glycerol!Phosphate!Shuttle!:!1!mole!of!glucose!8>!30!moles!of!ATP! 2.! Malate!–!Aspartate!Shuttle:!1!mole!of!glucose!8>!32!moles!of!ATP! ! ! ! ! ! ! ! ! X.! THE/TRICARBOXYLIC/ACID/CYCLE/(KREBS/CYCLE)/ ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! 8! 8! 8! ! Involves!the!oxidation!of!Acetyl!CoA!and!reduction!of!coenzymes!which!are!subsequently!reoxidized!to!produce! ATP! An!amphibolic!cycle!which!provides!carbon!skeletons!for!other!pathways! All!enzymes!utilized!by!the!TCA!are!found!in!the!miyochondrial!matrix!except!succinate!dehydrogenase!(inner! mitochondrial!membrane).! ! A.! Reactions/of/the/TCA/ ! 1.! Acetyl!CoA!and!Oxaloacetate!condense!to!form!Citrate! o! Catalyzed!by!Citrate!Synthase! o! The!reaction!is!inhibited!by!the!product,!Citrate! 2.! Isomerization!of!Citrate!to!Isocitrate! o! Catalyzed!by!Aconitase! 3.! Isocitrate!undergoes!oxidation!to!form!α!8!ketoglutarate! o! Catalyzed!by!Isocitrate!Dehydrogenase! o! CO2!is!produced!! o! Electrons!are!passed!to!NAD+!to!form!NADH!! 4.! α!8!ketoglutarate!is!converted!to!Succinyl!CoA! o! Catalyzed!by!α!8!Ketoglutarate!Dehydrogenase! 5.! Succinyl!CoA!is!cleaved!to!Succinate! o! Catalyzed!by!Succinate!Thiokinase!(Succinyl!CoA!Synthetase)! 6.! Succinate!is!oxidized!to!fumarate! o! Catalyzed!by!Succinate!Dehydrogenase! o! Succinate!transfers!two!protons!to!FAD!to!form!FADH2! 7.! Fumarate!is!converted!into!Fumarase! o! Catalyzed!by!Fumarase! 8.! Malate!is!oxidized!to!regenerate!Oxaloacetate! o! Catalyzed!by!Malate!Dehydrogenase! o! Two!protons!and!electrons!are!transferred!to!NAD+!to!produce!NADH! ! ! ! 8! Total!ATP!Produced!for!every!cycle!utilizing!one!mole!of!Acetyl!CoA:!10!moles!of!ATP! o! For!every!mole!of!NADH!=!2.5!moles!of!ATP! !! 3!moles!per!cycle!=!7.5!ATPs! o! For!every!mole!of!FADH2! !! 1!mole!per!cycle!=!1.5!ATP! o! 1!ATP!from!the!GTP!produced!upon!cleavage!of!Succinyl!CoA! XI.! ! GLYCOGEN/METABOLISM/ / Glycogen! o! Composed!of!α81,48!linked!D!glucose!residues!with!branches!that!are!attached!by!α81,68!linkages! o! Liver!Glycogen!is!used!to!maintain!blood!glucose!during!fasting!and!exercise! o! Muscle!Glycogen!is!used!to!generate!ATP!for!muscle!contraction! ! A.! Glycogenisis/ / 1.! Synthesis!of!UDP!–!glucose! o! UDP!–!glucose!is!the!precursor!to!glycogen!synthesis! o! Glucose!enters!the!cell!and!converted!to!G6P!by!hexokinase!or!glucokinase! o! Phosphoglucomutase!converts!G6P!to!G1P! o! G1P!reacts!with!uridine!triphosphate!to!form!UDP!–!Glucose! 2.! Glycogen!synthase!transfers!glucose!residues!from!UDP!–!glucose!to!the!nonreducing!ends!of!a!glycogen! primer! 3.! Branch!Formation! o! When!a!chain!formed!contains!more!than!11!glucose!residues,!6!to!8!residues!in!length!is!removed!from! the!non!reducing!end!and!is!reattached!via!an!α81,68!linkages!to!a!glucose!residue!within!an!α81,48! linked!chain! o! Glucosyl!4:6!transferase!is!a!branching!enzyme!that!breaks!α81,48!bond!and!forms!an!α81,6!bond.!! 4.! Glycogen!synthase!continuously!adds!glucose!residues!to!the!nonreducing!ends! 5.! Additional!branches!are!formed!by!the!branching!enzyme! ! B.! Glycogenolysis! 8! Glycogen!can!be!degraded!in!the!lysosomes!by!the!enzyme!α8!Glucosidase! ! 1.! Glycogen!Phosphorylase!successively!cleaves!α81,48!bonds!to!produce!glucose!18phosphate!(G1P)!units!until! four!glucose!units!from!an!α81,68!branch!remains! 2.! The!remaining!four!units!are!removed!by!the!debranching!enzyme!(glucosyl!4:4!transferase!and!an!α81,68! glucosidase!activity)! 3.! Three!glucose!residues!from!the!remaining!four!units!will!be!removed!as!a!trisaccharide!and!will!be!attached! to!a!nonreducing!end!of!another!chain!by!a!4:4!transferase!cleaving!the!old!and!forming!a!new!α81,48!bond! 4.! The!remaing!glucose!residue!with!an!α81,6!linkage!will!be!hydrolyzed!by!the!anzyme!α81,68glucosidase!to! form!a!free!glucose.!! ! C.! Glycogen/Storage/Diseases/ / TYPE/ 0/ NAME/ GSD/0/ DEFICIENCY/ Glycogen!Synthase! I/ Von/Gierke/Disease/ Glucose!6!–!Phosphatase! II/ Pompe/Disease/ Lyosomal!Storage!Disease! Manifestation/ Results!in!fasting! hypoglycemia!with! occasional!muscle! cramping! Results!in!ntracellular! accumulation!of!glucose!6! phosphate!and!severe! hypoglycemia! ! Hepatomegaly,!platelet! dysfunction!and!growth! retardation! Accumulation!of!glycogen! within!the!lysosome! ! IIa!–!Infantile!form!that! presents!with!muscle! wakness!that!may!cause! heart!muscle!dysfunction! ! ! ! III/ Cori/Disease/ Deficiency!from! Debranching!Enzyme! IV/ Andersen/Disease/ Glucosyl!4:6!transferase! V/ McArdle/Disease/ Muscle/Phosphorylase/ VI/ Hers/Disease/ Partial/deficiency/of/Liver/ Phosphorylase/ *IIb!–!Juvenile!Form! ! *IIc!–!Adult!form! ! *skeletal!muscle!weakness! Hepatomegaly,! Hypoglycemia!during! fasting,!Myopathy! Glycogen!has!very!long! outer!branches!which!leads! to!death!within!5!years!of! age! Exercise!induced!cramps! secondary!to! rhabdomyolysis! Extreme!enlargement!of! the!liver!resulting!from! glycogen!accumulation.! ! XII.! GLUCONEOGENESIS/ / 8! 8! 8! 8! 8! Main!site!of!reaction:!Liver! o! Hepatic!gluconeogenesis!is!inhibited!by!biguanides!that!decreases!the!circulating!glucose!concentration! Synthesis!of!Glucose!from!non!–!carbohydrate!sources! Major!Precursors:!Lactate,!Amino!Acids,!and!Glycerol! Insulin!and!Glucagon!mainly!regulates!blood!glucose! o! Insulin!stimulates!the!transport!of!glucose!into!the!adipose!and!muscle!cells! o! Type!I!DM:!Insulin!Dependent!;!Type!II!DM:!Non!–!insulin!Dependent! o! Thiazolidinediones!induce!genes!that!increase!cell!responsiveness!towards!circulating!insulin! o! Sulfonylureas!stimulate!the!release!of!preformed!insulin!to!prevent!hyperglycemia! o! Glucagon!level!increases!during!fasting!state!and!stimulates!gluconeogenesis! Glucagon!is!elevated!in!fasting!state!which!stimulates!Gluconeogenesis! ! A.! Steps/in/Gluconeogenesis/ ! 1.! Pyruvate!is!converted!to!Oxaloacetate!by!the!enzyme!pyruvate!carboxylase! 2.! Oxaloacetate!is!decarboxylated!by!Phosphoenolpyruvate!Carboxykinase!to!form!PEP! 3.! PEP!is!converted!to!Fructose!1,6!–!bisphosphate! 4.! Fructose!1,68Biphosphate!is!converted!to!Fructose!6!–!Phosphate!by!the!enzyme!Fructose!1,68!Biphosphate! 5.! Fructose!68Phosphate!is!converted!into!G6P! 6.! G6P!releases!an!inorganic!phosphate!that!produces!free!glucose!catalyzed!by!Glucose!68Phosphatase! / / ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! XIII.! LIPIDS/AND/FATTY/ACIDS/ ! A.! 8! 8! 8! Fatty/Acids/ Exists!freely!in!the!body!in!their!unesterified!form!and!fatty!acyl!esters!such!as!Triacylglycerol!(TAG)! Consist!of!a!hydrophobic!hydrocarbon!chain!with!a!terminal!carboxyl!group! Fatty!acids!present!in!the!human!usually!contains!an!even!number!of!carbon!atoms!(16!820)!that!can!either!be! saturated!or!unsaturated!(with!double!bond)! ! 1.! Essential!Fatty!Acids! o! Linoleic!Acid!(18:2!(9,12))!serves!as!the!precursor!of!Arachidonic!Acid! o! Provided!by!daily!diet! ! 2.! Fatty!Acid!Synthesis! ! a.! Glucose!is!converted!into!Acetyl!CoA!to!supply!the!Carbon!needed!for!fatty!acid!synthesis!occurring!in! the!cytosol! b.! The!fatty!acid!synthase!(multienzyme!complex)!in!the!cytosol!initiates!the!synthesis!utilizing!2!acetate! units!from!the!Acetyl!–!CoA!pool! c.! Addition!of!2!Carbon!Units! !! Acetyl!CoA!reacts!with!the!phosphopantetheinyl!residue,!transferring!the!ecetyl!group!to!the! cysteinyl!residue! !! A!thioester!is!formed!between!a!malonyl!unit!and!the!phosphopantetheinyl!sulhydryl!group! !! The!acetyl!group!on!the!fatty!acid!synthase!condenses!with!the!malonyl!group! !! CO2!will!be!released!from!the!malonyl!group! !! A!β!8!ketoacyl!group!with!four!carbons!is!produced! d.! Reduction!of!the!β!8!ketoacyl!group!! !! !Reduced!to!a!β!8!hydroxyl!group!by!NADPH! !! A!double!bond!is!added!between!Carbons!2!and!3!via!dehydration! !! NADPH!reduces!the!double!bond!to!form!a!four!8!carbon!acyl!group! e.! Elongation!of!the!growing!FA!Acyl!Chain! !! The!acyl!group!is!transferred!to!the!cysteinyl!sulfhydryl!group! !! Malonyl!CoA!reacts!with!phosphopantetheinyl!group! !! The!acyl!and!malonyl!groups!release!CO2!via!condensation! !! Reduction!of!the!β!8!keto!group!! !! The!reaction!continues!until!a!16!–!Carbon!FA!is!produced! f.! Palmitate!is!the!final!product!released!via!hydrolysis! !! Palmitate!can!undergo!further!elongation!and!desturation!to!form!longer!saturated!and! unsaturated!FAs! ! 3.! β!8!Oxidation!of!Even!–!Numbered!FA’s! o! FA’s!are!activated!in!the!cytosol!by!ATP!and!CoA!to!form!Fatty!Acyl!CoA! o! Reaction!happens!in!the!mitochondria! o! Energy!generating!(ATP!producing)! o! Computing!for!the!ATPs!produced!(Palmitic!Acid!for!example!(16!Carbons)):!! !! Compute!for!the!number!of!Acetyl!CoA!formed:! ¥! Number!of!Carbons/2! ¥! 16/2! ¥! 8!moles!of!Acetyl!CoaA! !! Compute!for!the!number!of!rounds!to!complete!1!cycle:! ¥! Number!of!Acetyl!CoA!formed!–!1! ¥! 8!81! ¥! 7!Rounds! !! Granting!that!each!NADH!yields!2.5!ATP!and!each!FADH2!yields!1.5!ATP,!multiply!the!number!of! rounds!by!4!(the!number!of!NADH!and!FADH2!is!equal!to!the!number!of!rounds!to!complete!1! cycle):! ¥! 7!x!4! ¥! 28!ATPs! o! 17.5!ATPs!from!NADH!! !! 7!moles!of!NADH!x!2.5! o! 10.5!ATPs!from!FADH2! !! 7!moles!of!FADH2!x!1.5! !! Multiply!the!number!of!Acetyl!CoA!formed!by!10:! ¥! 8!x!10! ¥! 80!ATPs! !! Subtract!2!from!the!total!since!2!ATPs!were!used!for!the!activation!of!the!FA:! ¥! (80!+!28)!–!2!=!106!ATPs!produced!for!Palmitic!Acid! ! B.! Phospholipids/ 8! These!are!polar,!ionic!compounds!made!up!of!alcohol!attached!to!a!sphingosine!or!diacylglycerol!via!a! phosphodiesterbond/ / 1.! Glycerophospholipids! o! Contains!glycerol!and!are!the!predominant!lipids!in!membranes! o! Cardiolipins,!Plasmalogens,!Platelet!–!Activating!Factor! ! 2.! Sphingophospholipids! 8! Contains!ceramide!with!various!groups!attached!to!it! ! o! Sphingomyelin! !! Contains!phosphocholine! o! Cerebrosides! !! Has!one!sugar!residue! o! Gangliosides! !! More!than!1!sugar!residue! ! XIV.! CHOLESTEROL/ / A.! Synthesis/ 8! Precursor:!Cytosolic!Acetyl!CoA! ! a.! Cytosolic!Acetyl!CoA!forms!acetoacetyl!CoA!and!condenses!with!another!acetyl!CoA!forming!HMG!–!CoA! b.! Cytosolic!HMG!–!CoA!is!reduced!to!mevalonic!acid!by!HMG!–!CoA!reductase! !! Statins!act!as!competitive!inhibitors!of!HMG!–!CoA!reductase! c.! Mevalonic!Acid!undergoes!phosphorylation!and!decarboxylation!to!form!isopentyl!phyrophosphate! which!is!a!five!carbon!isoprenoid! d.! Isopentyl!pyrophosphate!forms!geranyl!pyrophosphate!(C810)!via!condensation!which!reacts!with! another!C85!unit!to!form!farnesyl!pyrophosphate!(C815)! e.! Two!units!of!farnesyl!pyrophosphate!combines!to!form!Squalene! f.! Squalene!undergoes!oxidation!and!cyclization!to!from!lanosterol! g.! Lanosterol!is!converted!to!Cholesterol! !! Steroid!hormones!are!synthesized!from!cholesterol! ! B.! Bile/Salts! 8! Bile!salts!are!synthesized!in!the!liver!from!cholesterol!and!secreted!via!the!bile!through!the!gallbladder!into!the! intestine!which!aids!in!lipid!digestion! o! Bile!acid!sequestrants!such!as!cholestyramine!bind!with!bile!acids!present!in!the!intestinal!lumen!! 8! Primary!Bile!Salts:!Cholic!Acid,!Chenocholic!Acid! ! C.! Blood/Lipoproteins/ o! Chylomicrons! !! Least!dense!with!the!least!amount!of!protein!but!has!the!highest!amount!of!TAG! ! o! Very!–low!density!lipoprotein!(VLDL)! !! More!dense!than!chylomicrons!but!still!has!a!high!amount!of!TAG! !! Synthesized!in!the!liver!specifically!after!a!high!carbohydrate!meal! !! Digested!by!lipoprotein!lipase!and!conerted!to!IDL! ¥! Fibrates!such!as!gemfibrozil!activates!the!transcription!of!lipoprotein!lipase!by!activating! the!PPAR!receptors! ! o! Intermediate!–!low!density!lipoprotein!(IDL)! !! Denser!than!VLDL!but!Has!less!than!half!of!the!amount!of!TAG!as!compared!to!VLDL! ! o! Low!density!lipoprotein!(LDL)! !! Lesser!Tag!content!than!IDL!and!has!more!protein! !! Has!the!highest!content!of!cholesterol! ! o! High!density!lipoproteins!(HDL)! ! ! ! ! ! ! !! The!densest!lipoprotein!with!the!lowest!TAG!content!and!has!the!highest!amount!of!protein! ! XV.! OTHER/LIPID/DERIVATIVES/ / A.! Ketone/Bodies! 8! Synthesized!in!the!liver!mitochondria!when!there!is!an!increased!concentration!of!FAs!in!the!blood!which!is! observed!during!starvation,!fasting,!or!high!fat!diet! o! During!starvation,!increased!concentration!of!ketone!bodies!in!the!blood!permits!entry!to!the!brain!and! undergo!oxidation! 8! Taken!up!by!peripheral!tissues:!Muscles!and!Kidney! 8! Oxidation!of!ketone!bodies!produces!energy! ! B.! Sphingolipids! 8! Derived!from!Serine! 8! Degraded!by!lyosomal!enzymes!where!defiency!of!such!enzymes!causes!mild!to!severe!diseases! ! Disease/ Niemann!–!Pick!Disease! Deficient/Enzyme/ Sphingomyelinase! Acuumulated/Products/ Sphingomyelin!in!both! brain!and!blood!cells! Fabry!Disease! α!8!Galactosidase!A! Krabbe!Disease! β!8!Galactosidase! Glycolipids!in!the!brain,! heart,!and!kidney!causing! ischemia! Glycolipids!which!causes! destruction!of!myelin!–! producing! oligodendrocytes! Gaucher!Disease! Glucocerbrosidase! Glucocerbrosides!in!the! blood!cells,!liver,!and! spleen! Tay!–!Sachs!Disease! Hexosaminidase! GM2!gangliosides!in! neurons! Manifestation/ Mental!retardation,! spasticity,!and!ataxi! resulting!to!death!by!age!3! Acroparesthesia,!skin! lesions,!and!hipohidrosis! Spasticity!and!rapid! neurodegeneration.! Hypertonia,!hyperreflexia,! decerebrate!posturing,! blindness,!and!deafness! Hepatosplenomegaly,! Thrombocytopenia,! specifically!prevalent!in! Ashkenazi!Jews! Progressive! neurodegeneration,! developmental!delay!and! death.!! ! XVI.! AMINO/ACID/METABOLISM/AND/PRODUCT/FORMATION/ / A.! Nitrogen// 8! Amino!acids!undergo!reactions!wherein!the!Nitrogen!moiety!is!converted!into!ammonia!or!ammonium!as! product/ 8! Ammonia!is!very!toxic,!specifically!to!the!CNS/ 8! Ammonia!enters!the!Urea!cycle!to!form!urea!an!is!excreted!by!the!kidneys/ / B.! Synthesis/of/Amino/Acids/ / 8! 8! 8! Amino!Acids!derived!from!Glucose:! o! Serine,!Glycine,!Cysteine,!Alanine,!Glutamic!Acid,!Glutamine,!Aspartic!Acid,!Asparagine,!Proline,!Arginine! Essential!amino!Acids!(derived!from!daily!diet):! o! Histidine,!Isoleucine,!Leucine,!Lysine,!Methionine,!Phenylalanine!(from!Tyrosine),!Threonine,! Tryptophan,!Valine! Amino!Acids!derived!from!TCA!Cycle!intermediates! o! Aspartate,!Asparagine,!Glutamate! ! C.! Degradation/of/Amino/Acids/ / 8! 8! Amino!acids!that!form!pyruvate!or!intermediates!of!the!TCA!in!the!liver!are!glucogenic! o! Provides!carbon!for!glucose!synthesis! o! Alanine,!Arginine,!Asparagine,!Aspartic!Acid,!Cysteine,!Glutamic!Acid,!Glutamine,!Glycine,!Histidine,! Methionine,!Proline,!Serine,!Valine! Amino!Acids!that!form!Acetyl!CoA!are!ketogenic! 8! ! ! ! o! Forms!ketone!bodies! o! Leucine!and!Lysine! Amino!Acids!that!are!both!ketogenic!and!glucogenic! o! “PITTT”! o! Phenylalanine,!Isoleucine,!Threonine,!Tryptophan,!Tyrosine! 8! 8! D.! 8! E.! 8! F.! 8! 8! 8! G.! 8! Degradation!of!branched!amino!acids!is!catalyzed!by!the!branched!–!chain!α!8!ketoacid!dehydrogenase!complex! o! A!defect!in!the!enzyme!complex!(α!8!ketoacid!dehydrogenase)!causes!the!accumulation!of!Valine,! isoleucine,!and!Leucine!in!the!blood.!! !! Maple!Syrup!Urine!Disease! !! Urine!has!a!characteristic!Maple!Syrup!odor! !! Causes!mental!retardation!and!poor!nerve!myelination! Phenylalanine!is!converted!into!Tyrosine!by!phenylalanine!hydroxylase! o! A!defect!in!phenylalanine!hydroxylase!prevents!the!conversion!of!Phe!to!Tyr! !! Phenylketonuria! !! Characterized!by!a!urine!with!musty!odor! !! Leads!to!mental!retardation! Creatine/ from!glycine,!arginine!and!S8adenosylmethionine/ / Glutathione/ A!tripeptide!formed!from!glutamate,!cysteine,!and!glycine! / Decarboxylation/products/ GABA! o! A!major!inhibitory!neurotransmitter!from!the!decarboxylation!of!glutamate! Histidine! o! From!the!decarboxylation!of!Histidine! o! Causes!vasodilation!and!bronchoconstriction!and!stimulates!the!secretion!of!HCl!in!the!GIT! !! H1!receptors!are!found!in!the!GIT,!H2!receptors!trigger!allergic!reactions! Serotonin! o! From!the!decarboxylation!of!Tryptophan! o! Stimulatory!neurotransmitter!involved!in!mood!regulation! ! Melanin/ Produced!from!Tyrosine!upon!the!action!of!Tyrosinase/ o! Albinism!results!to!the!deficiency!of!Tyrosinase/ !! Characterized!by!the!absence!of!pigment!in!the!hair,!skin,!and!eye/ / H.! Xanthine!is!oxidized!to!Uric!acid!by!xanthine!oxidase!and!is!excreted!by!the!kidneys.!/ / XVII.! DIET/&/NUTRITION/ / A.! /Carbohydrates/ 8! Sourced!out!from!daily!intake!of!simple!and!refined!sugars,!and!starches! 8! Constitutes!45!–!65!%!of!the!total!daily!caloric!intake! ! B.! Lipids/ 8! Daily!caloric!intake!should!contain!no!more!than!30%!of!Fats/ 8! Cholesterol!intake!should!not!exceed!300!mg/day/ / Number/of/Carbon/Atoms// Name/of/Fatty/Acid/ Double/Bonds/ 4! Butyric!Acid!(C4:0)! None! 6! Caproic!Acid!(C6:0)! None! 8! Caprylic!Acid!(C8:0)! None! 10! Capric!Acid!(C10:0)! None! 12! 14! Lauric!Acid!(C12:0)! Myrisitic!Acid!(C14:0)! None! None! 16! Palmitic!Acid(C16:0)!! None! 16! 18! Palmitoleic!Acid!(C16:1,!Omega!7)! Stearic!Acid!(C18:0)! Carbon!9! None! 18! 18! Oleic!Acid!(C18:1,!Omega!9)! Linoleic!Acid!(18:2,!Omega!6)! Carbon!9! Carbon!9,!12! 18! α!8!Linolenic!Acid!(18:3,!Omega!3)! Carbon!9,12,15! 20! Arachidic!Acid!(C20:0)! None! 20! Arachidonic!Acid!(C20:4)! Carbon!5,8,11,14! / / / / C.! Proteins/ 8! Recommended!daily!intake!is!0.8g/Kg!body!weight/ 8! Kwashiorkor!Disease/ o! Caused!by!a!low!protein!diet!and!characterized!hepatomegaly/ 8! Marasmus/ o! Caused!by!a!diet!deficient!from!protein!and!calories/ / D.! Water/Soluble/Vitamins/ / 1.! Vitamin!B1!(Thiamine)/ o! Acts!as!cofactor!for!pyruvate!and!α8ketoglutarate!dehydrogenase! o! Beriberi/ !! Characterized!by!high!output!heart!(Wet!type)!failure!and!peripheral!neuropathy!(Dry!Type)/ o! Wernicke!–!Korsakoff!Syndrome/ !! Manifested!by!ataxia,!ophthalmoplegia!and!confabulation/ / 2.! Vitamin!B2!(Riboflavin)/ o! Precursor!to!Flavin!Adenine!Dinucleotide!(FAD)! o! Common!sources!are!grain!and!cereal!products!fortified!with!riboflavin! o! Deficiency!is!manifested!by!glossitis!and!cheilosis! ! ! 3.! Vitamin!B3!(Niacin)/ o! Needed!for!the!production!of!NAD!and!NADP! o! Pellagra! !! Characterized!by!diarrhea,!dementia,!and!dermatitis! o! Deficiency!can!result!from!Isoniazid!intake! ! 4.! Vitamin!B6!(Pyridoxine)/ o! Utilized!in!transamination!and!decarboxylation!reactions/ o! Deficiency!can!result!from!Isoniazid!intake! / 5.! Vitamin!B12!(Cobalamin)/ o! Required!by!Methmalonyl!CoA!mutase!and!Methionine!synthase! o! Deficiency!blocks!the!purine!and!thymidine!biosynthesis!resulting!to!megaloblastic!anemia! ! 6.! Biotin! o! Utilized!in!carboxylation!reactions! o! Produced!by!gastrointestinal!bacteria! o! Deficiency!may!be!caused!by!long!term!antibiotic!use! ! 7.! Folate! o! Reduced!to!Tetrahydrofolate!which!act!as!one!–!carbon!donor!in!different!pathways! o! Pregnant!women!who!are!deficient!from!folate!causes!the!fetus!to!suffer!from!Spina!Bifida! o! Can!be!sourced!out!from!dark!leafy!vegetables! ! 8.! Vitamin!C!(Ascorbic!Acid)! o! Aids!in!the!hydroxylation!of!proline!in!collagen!! o! Aids!in!iron!absorption! o! Acts!as!an!antioxidant! o! Scurvy! !! Characterized!by!easy!bruising,!muscular!fatigue,!hemorrhage!and!swollen!gums! ! E.! Fat/–/Soluble/Vitamins/ / 1.! Vitamin!K!! o! K1!=!exists!as!Phylloquinone!in!plants! o! K2!=!exists!as!Mendaione!!in!intestinal!bacterial!flora! o! Vitamin!K!is!highly!involved!in!activating!precursors!of!prothrombin!and!other!clotting!factors!via!the! carboxylation!of!glutamate!residues! ! 2.! Vitamin!A!(Retinol)! o! Essential!for!vision,!reproduction,!growth,!and!maintenance!of!epithelial!tissue! o! Can!refer!to!several!related!active!molecules! !! Retinol! !! Retinal! !! Retinoic!Acid! ¥! Retinoic!acids!and!its!derivatives!(Isotretinoin)!can!be!used!for!treating!dermatologic! diseases! !! β!8!Carotene! ! 3.! Vitamin!E! o! Consist!of!8!naturally!occurring!tocopherols!having!the!α!8!tocopherol!as!the!most!active!form.! o! Acts!as!an!antioxidant! ! 4.! Vitamin!D! o! Refers!to!a!group!of!sterols!which!act!as!hormones! o! Highly!present!in!Fatty!fish,!liver,!and!egg!yolk! o! The!precursor,!7!–!Dehydrocholesterol,!is!converted!into!Cholecalciferol!in!the!dermis!and!epidermis!of! humans!after!sunlight!exposure! o! Vitamin!D2!=!Ergocalciferol!! !! Present!in!plants! o! D3!=!Cholecalciferol! !! Present!in!animal!tissues! o! D2!and!D3!are!converted!to!the!active!form!1,25!–!Dihydrocholecalciferol! o! Rickets! !! Deficiency!of!Vitamin!D!in!children!manifested!by!incomplete!mineralization!of!the!forming!bone! o! Osteomalacia! !! Deficiency!of!Vitamin!in!adults!manifested!by!increased!risk!of!bone!demineralization! / / XVIII.! GENETICS/ / A.! Chromosomes/ 8! DNA!is!organized!into!chromosomes!in!the!human!body! 8! The!normal!somatic!cells!in!the!body!are!diploid!with:! o! 46!Chromosomes! !! 22!pairs!of!autosomes! !! 1!Pair!of!Sex!chromosomes! 8! Mature!gametes!(sex!cells)!contains!a!haploid!number!of!chromosomes! o! 22!Autosomes! o! 1!Sex!chromosome,!either!X!or!Y!chromosome! 8! The!combination!of!DNA!and!protein!forms!a!Chromatin! 8! Sex!Chromosomes!dictate!the!gender!of!the!fetus! o! XY!(male)! o! XX!(female)! o! An!excess,!or!lack!of!these!chromosomes!can!cause!disorders! !! 45X0:!Turner!Syndrome! !! 47XXY:!Klinefelter!Syndrome! !! 47XYY:!XYY!Syndrome! ! B.! Cell/Cycle! 8! Cells!give!rise!to!two!identical!daughter!cells! ! 1.! Interphase! 8! Divided!into!3!phases!befor!the!cell!undergoes!Mitosis! a.! G1! !! Point!of!entry!for!cells!into!the!cell!cycle! !! Production!of!proteins!needed!for!the!cell!cycle! b.! S! !! Synthesis!of!DNA!via!semiconservative!replication! c.! G2! !! Preparation!for!Mitosis!with!continuous!protein!and!organelle!synthesis! !! Resulting!DNA!is!assessed! 2.! Mitosis! 8! The!process!of!nuclear!division! ! a.! Prophase! !! Chromatins!condense!! !! Structural!proteins!(Centrioles)!start!to!move!towards!the!opposite!poles!of!the!cell! ! b.! Metaphase! !! The!most!visualized!stage!in!Mitosis! !! Sister!chromatids!line!up!along!the!equatorial!plane! ! c.! Anaphase! !! “Action!Stage”! ! The sister chromatids separate into two equal parts, ensuring equal genetic material ! d.! Telophase! !! Chromosomes!decondense!and!formation!of!a!nuclear!membrane!encapsulates!the!separated! genetic!material! !! Cytokinesis!follows! ¥! The!plasma!membranes!pinch!–!off!and!forms!two!daughter!cells! C.! Meiosis/ 8! The!reductive!division!of!diploid!chromosomes!to!form!haploid!chromosomes! 8! For!gametes! 8! Involves!Meiosis!I!and!Meiosis!II! ! 1.! Meiosis!I! o! Separation!of!a!homologous!chromosome!pairs!that!forms!two!diploid!cells! ! a.! Prophase!I! !! Duplicate!chromatin!condenses!with!each!chromosome!containing!two!sister!chromatids! !! A!tetrad!is!formed! ¥! 2!chromosomes,!4!chromatids!held!together!by!a!Chiasmata! b.! Metaphase!I! !! The!tetrads!attach!to!the!meiotic!spindle!and!align! ! c.! Anaphase!I! !! The!tetrads!divide!and!move!to!the!opposite!poles!composed!of!two!chromatids!each! ! d.! Telophase!I! !! Nuclear!membranes!forms!completing!the!division! ¥! In!Spermayogenesis,!equal!division!happenes! ¥! In!Oogenesis,!unequal!division!happens,!forming!a!larger!primary!oocyte!and!a!polar! body! 2.! Meiosis!II! 8! The!cell!division!continues!with!the!exemption!of!DNA!synthesis! 8! Goes!through!Prophase!II!until!a!cell!containing!a!haploid!number!of!chromosomes!is!produced! 8! Failure!of!sister!chromatids!to!separate!results!to!daughter!cells!with!an!abnormal!number!of!chromosomes!that! leads!to!different!disorders! o! Trisomy!21:!Down!Syndrome! o! Trisomy!13:!Patau!Syndrome! o! Trisomy!18:!Edwards!Syndrome!! / / XIX.! MISCELLANEOUS/ ! A.! Cancer/ 8! Proto8!oncogenes/ o! These!are!normal!proteins!that!regulates!growth!and!development/ 8! Oncogenes/ o! Misexpressed!or!mutated!proto!–!oncogenes!become!oncogenes!and!start!to!grow!uncontrollably/ 8! Overexpression!of!the!growth!factor!receptor!HER2/neu!is!commonly!associated!to!the!development!of!breast! CA/ 8! The!most!commonly!mutated!oncogene!in!CA!is!the!ras!gene/ 8! Human!papilloma!virus!(HPV!–!16!and!HPV!–!18)!are!closely!associated!to!cervical!CA/ 8! BRCA'–'1'and'BRCA62!genes!are!associated!with!breast!and!ovarian!CA/ / B.! Separating/the/DNA/ / 1.! Gel!Blotting! 8! The!molecules!such!as!DNA!are!subjected!to!electrophoresis!allowing!the!migration!of!the!components!within!an! electric!field.! 8! After!electrophoresis,!separated!molecules!will!be!blotted!using!a!nitrocellulose!filter!and!will!be!visualized!with! the!aid!of!a!solution!containing!a!probe.! ! o! Western!Blot! !! Proteins!are!separated!by!gele!electrophoresis!and!probed!with!antibodies!that!bind!a!specific! protein! o! Southern!Blot! !! A!radioactive!DNA!probe!hybridizes!with!DNA!! !! Detects!DNA!mutations! o! Northern!Blot! !! A!radioactive!DNA!probe!hybridizes!with!RNA!