biochemistry exam 1 review

7/25/2019 Biochemistry Exam 1 Review

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Biochemistry Exam 1 Review

Intro to Biomolecules:

Evolutionary Timeline:

Energy Charge:

High = anaerobic (all ATP)

ATP generating pathway isinhibited and ATP utiliing pathwayis activated

!ow = catabolic (all A"P)


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Salivary Buffering:

pH = #log$H%&

Each increase in ' unit o pH is '#old dierence in H% concentration

Henderson Hasselbalch:

*soelectric Point: (p+' % p+,)-,

./ ml saliva produced daily

o 0ubmandibular: 12

o Parotid: 32

o 0ublingual: 4/2

5erostomia: dry mouthgingivitis % caries

0aliva:

o Contains amylase % lipase

o 0ecretions stimulated by sympathetic and parasympathetic

o 667/2 water with electrolytes

o "ucus

o Anitmicrobial compounds (lactoerrin8 *gA8 lysoyme

o 9piorphin: pain#illing protease inhibitor

0aliva ;uering:


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Amino Acid:

aline

o !eucine

o *soleucine

o Phenylalanine

o Tryptophan

o "ethionine

o Proline (pyrrolidene ring)

?ncharged Polar side chain:

o 0erine

o Threonine

o Tryosine

o Asparagine

o lutamine

o Cysteine Acidic 0ide Chain:

o Aspartic Acid

o lutamatic Acid

;asic 0ide Chain:

o Histidine

o !ysine


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o Arginine

Hydrogen ;ond can be ormed by:

o 0er

o Thr

o Asn

o ln Cysteine orms disulide bonds

Amino acids and glucose are transported together with


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o mainly glycine and proline that are stabilied by h bonds

o reverse direction o polypeptide bacbone

Gotation can occur between peptide groups in proteins

o Gotated around alpha Carbon

o Phi angle has nitrogen

o Psi angle has carbonyl Protein olding promoted by chaperone proteins Hsp.8 Hsp6 (heat shoc)

?biBuitin:

o * protein damaged8 ubiBuitin helps with proteolysis

o Damaged protein is labelled with ubiBuitin

o ?biBuitin allows proteasome to recognie misiled protein

o !abelled protein gets cleaved into smaller peptides

0eBuence o amino acids o a protein will determine how it will old7 Iill go towards native

state (lowest ree energy)

"isolded Protein Diseases:

o Alheimerso Prion (mad cow disease and Creuteldt#Jaob)abnormal prion protein

Enyme !atalysis:

Enyme


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o ' atm

o pH .7

o *nitial concentrations o '" or all reactants and products

Geaction rate increases linearly with temperature until certain point8 then decreases

0ubstrate binding in active site o trypsin#lie serine proteases:

o Catalytic triad: A0P#',8 H*0#/.8 0EG#'6/o H*0#/. deprotonates deprotonates serine

o Hydro@yl group o series mediates catalysis

o 9@ygen rom serine attacs peptide bond

o Aspartic Acid stabilies peptide with negative carbo@yl group

o Iater comes in and hydrolyes peptide bond

o L0peciic site is only or !ysine or Arginine

Enyme "inetics:

"ichaelis#"enton:


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>ma@ is proportional to enyme amount (more enyme8 higher >ma@)

+m = substrate concentration when reaction velocity is M >ma@o Does not change with changing enyme

o 0maller +m = higher ainity or enyme

!ow concentration o substrate$0& 4 +mirst order reaction

High concentration o substrate$0& N +mero order reaction

!ineweaver#;ur plot: (double reciprocal plot)

o Competitive *nhibitor:

>ma@ doesnOt change (y intercept same)

+m changes (@#intercept changes)

Drugs: statin8 pravastatin

o ma@ changes (y#intercept changes)

+m stays the same (@#intercept same)

Drugs: Etravirine (H*> reverse transcriptase inhibitor)

Enyme Inhi#ition and $rug $iscovery:

luoride concentration too high = dental luorosis

o Changes in cosmetic: whiteyellow

He@aluorosilicic Acid: commonly used or water luoridation

9ptimal luoride !evels: 7.mg-!

luoride has , mechanisms to prevent caries:

o *nhibits Enolase:

Geduces lactate ormation by mouth bacteria (less

caries)

o luoroapatite (Ca/(P9)3) is teeth e@posed to luoride ions

Prevents decay

Does not dissolve in acids produced by bacteria


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Aspirin: (acetylsalicylic acid):

o *rreversible inhibitor o Cycloo@ygenase (C95)

o ;locs synthesis o prostaglandins % thrombo@anes

o *nhibits: *++Q

o Activates: A"P#activated Protein +inase

o Antithrombotic: prevents platelet ormation8 treats blood clots ;orteomib (;T)

o Anticancer drug or multiple myeloma % mantle cell lymphoma

"ultiple "yeloma: hematological neoplasm derived rom plasma cells that

prolierate into bone marrow

o Geversible Proteasome inhibitor

,1s proteasome has 1 catalytic Thr residues on Q subunit

o Causes accumulation o misolded *g in "ultiple "yeloma cells

Cell cycle is arrested

*nhibits activation o pro#survival transcription actor:


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o .thmost prescribed

9mepraole (Priloec):

o Antacid gastric proton pump inhibitor

o *rreversible inhibitor o stomach parietal cell H%-+% ATPase

o ?sually acidic in stomach due to proton pump

Protons (H%) in cytosol comes rom dissociation oH,9

H% pumped against gradient into stomach lumen

+% pumped against gradient into cytosol

9H# o dissociation o H,9 binds with C9, and

orms HC93# (bicarbonate) by carbonic anhydrase

o *rreversible b-@ orms disulide bond with cysteine in ATPase

Pravastatin (Pravachol) % 0imvastatin

o Competes with H"#CoA or active site o H"#CoA reductase

o or high cholesterol levels

Hydrocodone:

o Derived rom codeine

o Agonist or opioid receptor

%lycolysis:

' reactions

Aerobic: pyruvateacetyl CoA

Anaerobiclactic acid

*nsulin regulates !?T8 which taes in glucose to adipose-muscle

' o@idative step where


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He@oinase:

o Primary enyme or irst step

o High ainity or glucose

o *n !iver-pancrease8 glucoinase has high +m (low ainity)

Gate !imiting 0teps:

o 3 reactions involving He@oinase

P+ (most important)

*nhibitors: ATP8 citrate

Activators: A"P8 ,81#;P

Pyruvate +inase: activated by '81#;P


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%luconeogenesis:


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, pyruvates (3 carbon compound)glucose

Gate !imiting 0tep:

o Pyruvate Carbo@ylase

o PEP Carbo@yinase

o '81#;P

o lucose 1#Phosphatase GeBuires energy8 unlie glycolysis

9ccurs in !iver and +idney8 whereas glycolysis in all cells o body

Pyruvate Carbo@ylase is in mitochondrial matri@:

o GeBuires coenyme ;iotin

o Activated by acetyl CoA (regulatory mechanism)

o Turns pyruvateo@aloacetate

o 9AA"alate (leaves mito into cytosol)9AAPEP

0tarvation:

o !ots o beta#o@idationincreased acetyl CoA

o Acetyl CoA activates pyruvate carbo@ylaseincreased gluconeogenesis Energy GeBuirement:

o 1 ATP

o ,


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Phosphorylated (phosphatase activity)V ,81#;P

Diabetes:

o Type ': low levels o insulin

o Type **: resistant to insulin

o 0tarvationincreased gluconeogenesisincreased glucose *nsulin cannot stop this

o "uscle-adipose insulin dependent


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Pentose Phos&hate Pathway:

#1#P has 3 pathways:

o lycogen

o PPPo lycolysis

o luconeogenesis

unction o PPP:

o Provide


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lycogen unction and !ocation:

o *n well ed person8 concentration highest in !iver

o !iver storage depleted within , hrs o ast

o "uscle storage is less readily depletedo "ore total storage in uscles

o ;rain has low glycogen concentration

lycogen 0tructure:

o lucosyl residues Woined by glycosidic lins

S '# are main bacbone

S '#1 are branches at every K#', S linage

o Q '# are seen in cellulose

o * Wust S '# linage than it would be starch

lycogen 0ynthesis:

o #1#P is initially used to become lucose '#Phosphate (reversible) Enyme: phophoglucomutase

o #'#P becomes ?DP#glucose with addition o ?TP

Enyme: ?DP#glucose pyrophosphorylase

o ?DP#glucoseglycogen

;acbone ormed by lycogen 0ynthase

S '#1 branches ormed by Amylo '#8 '#1 Transglucosylase

o ormation o glycogen rom ?DP#glucose releases ?DP (uridine diphosphate)

lycogen ;readown:

o S '# broen down by lycogen Phosphorylase becomes #'#P (' per glucose)

Phosphorolytic cleavage

o S '#1 broen by lycogen Debranching Enymeree glucose

Hydrolytic recation

Has transerase activityoligosaccharide near branch point to S '# chain

Gegulation o lycogen "etabolism:

o lycogen 0ynthase (build): (dephosphorylated orm is active)

Activated: Protein Phosphatase:

*nsulin activates

*nactivated: Protein +inase

o lycogen Phosphorylase (brea): (phosphorylated orm is active)

Activated: Protein +inase

lucagon: activates rom liver

Epinephrine: activates rom muscles

*nactivated: Protein Phosphatase


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Epinephrine and lucagon use PCG Pathway:

o Adenylyl cyclase

o cA"P (degraded by phosphodiesterase to /A"P)

Phosphodiesterase inhibited by caeine

/A"P can activate glycogen phosphorylase without phosphorylation

During ano@ia or depletion o ATP

o Catalytic subunit rom cA"P can activate lycogen Phosphorylase +inase

Ca,% can activate by binding to calmodulin8 a subunit o glycogen

phosphorylase inase8 which then activates glycogen phosphorylase to causeglycogen degradation


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'ricar#oxylic Acid !ycle:

9@idation o carbs8 ats8 and amino acids via acetyl CoA

Products:

o C9,

o


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Pyruvate Dehydrogenase Comple@:

o *nhibitors:

Acetyl CoA (end product)


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Anaplerosis (illing up):

o Pyruvate Carbo@ylase occurs in gluconeogenesis in liver-idneys

o Pyruvate Carbo@ylase catalyes reaction between pyruvate and C9, to mae

9@aloacetateo Thus8 high levels o 9@aloacetate in !iver % +idneys

o Pyruvate Carbo@ylase is used to 9AA concentrations high

Gegulation o Tricarbo@ylic Acid Cycle:

o Pyruvate DH:

*nhibitor: ATP8


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Allosterism and Regulation of Enyme Activity:

0ubstrate Concentration vs7 Geaction >elocity

o Enyme ollowing "ichaelis#"entonhyperbolic curve

o Allosteric Enymesigmoid curve

0hows cooperativity

Hemoglobin:

o Tetramer (,S8 ,Q)

o Heme molecule noncovalently bonded to each subunito Heme allows o@ygen binding

o Allosteric

0ingle o@ygen molecule bounded = easier to bind more

Ainity or last 9,is 3@ than ainity or 'st9,

o Can bind o@ygen molecules

o Carries o@ygenunloads o@ygen8 taes up C9,


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o P/ value: ,1 torr

Partial pressure o o@ygen that will cause /2 saturation

Higher partial pressure in lungs than capillaries o muscles

E Hand

o 0tructure o enyme than binds Ca,%

o Calmodulin: ;inds calcium ions

Calmodulin#dependent enymes:

cA"P phosphodiesterase: degredation o cA"P

"yosin light chain inase: smooth muscle contraction

Calcineurin: phosphatase that taes phosphate o protein

Calcium-calmodulin depended protein inase **

Plasma membrane Ca,% ATPase

Gas:

o "onomeric guanine nucleotide binding protein

o N/2 chance o cancers have mutated Gas Activated XonY state allows unregulated cell prolieration

o TPase switch:

*nactive Gas: bound to DP

uanine E@change actor (E) allows TP to replace DP

Activator Protein

TPase Activator Protein (AP) allows Gas to hydrolye TP to DP

*nactivator Protein

Enyme Gegulation: phosphorylation %

dephosphorylation

o +inase puts phosphate to target protein (active) through hydrolying ATP to ADP

o Phosphatase taes o phosphate (inactive)

eedbac inhibition:

o ?sually end product o reaction acts as inhibitor o previous enymeo Gate limiting enyme oten aected

o E@: P+#' and Citrate:

Citrate is inal product o glucose metabolism

Citrate inhibits Phosphoructoinase#'8 which converts #1#P to '81#;P

ATP is also a eedbac inhibitor (high ATP = no need to metabolie glucose)

Enyme Gegulation: Hormones


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o *nsulin:

0timulates glycolysis

Geleased ater meal

Geceptor: tyrosine inase receptor

o lucagon:

*nhibits glycolysis Geleased in starvation

Geceptor: #protein coupled receptor

o ;oth *nsulin and lucagon act on:

lucoinase

Phosphoructoinase

Pyruvate +inase

Enyme levels oten elevated in plasma levels ater damage to tissues

"arers o !iver Disease:

o Alanine Aminotranserase (A!T)

o Aspartate Aminotranserase (A0T)o *ncreased ;ilirubin = liver disease

"arers o Heart Disease:

o Creatine +inase *soyme: rise ater myocardial inarction

o *soyme can be placed in electrophoresis:

*soyme has , orms: muscle and brain

, b subunits and , m subunits

o ;oth Creatine +inase "; and Cardiac Troponin are

increased in plasma ater myocardial inarction


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(eta#olic !om&artmentaliation:

0eries o Centriugations: (each round at aster speed)


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o 0mall molecules can use simple diusion (urea)

o Amino acid transport can be either acilitated or active

o


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Zield o ATP rom 9@idation o ' lucose:

o


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,xidative Phos&horylation:

Taes place in mitochondrial matri@

Taes H% rom


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H%

concentration accumulates in intermembrane space

9n inner membrane:

o ATP synthetase

H% goes bac into matri@ and ATP orms

o ATP-ADP antiporter ATP out

ADP in

o Phosphate Transporter:

9H# out (combines with H% in intermembrane space to orm H,9)

HP9,# in

*nhibitors o 9@idative Phosphorylation:


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o Comple@ ': Gotenone

o Comple@ ***: Antimycin A

Comple@ ' % , are reduced (upstream)

Comple@ c % 3 % are o@idied (downstream)

o Comple@ *>: Carbon "ono@ide % Cyanide

o Comple@ > (ATP synthase): 9ligomycino ATP-ADP Translocase (antiporter): Atractyloside

?ncouplers o 9@idative Phosphorylation:

o Dissipates proton gradient across inner membrane to prevent ATP synthesis

Protons are still moved into matri@ by uncoupler protein


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Hormonal Control o !ipid Digestion:

o 0tomach:

Cholecystoinin (CC+):

*hibits gastric motility

0timulates release o pancreatic enymes to release lipids

0imulates gallbladder to release bile

o ?pper 0mall *ntestine:

0ecretin:

0timulates pancreas to release bicarbonateincreases pH o lumen

enymes more eective

o CC+ and 0ecretin both released by gut endocrine cells when dietary lipids enter small

intestines

atty Acid Abosorption:

o *ntestinal mucosal cells absorb lipids

o ,#"onoacylglycerol gets reconverted bac to Triacylglycerol (TA)

o !ipids go into Chylomicron: TA

Cholesteryl ester

Apolipoprotein ;#K

Phospholipids

o Chylomicron goes into lymphatic system which eventually enters blood

atty Acid 0tructure:

o ,# Carbons: short chain

o 1#', Carbons: medium chain

#' carbons seen in mil

o '#, Carbons: long chain atty acids have at least '1 carbons

o N,, Carbons: very long#chain

o Palmitic Acid is written as '1:'1 carbons with unsaturated bonds

o 9leic Acid written as 'K:'(6)'K carbons8 ' unsaturated bond at 6thcarbon

o Essential atty Acids: !inoleic acid % S#!inolenic acid

o ormic Acid is simplest with ' carbon

Cis vs Trans atty Acids:

o Double bond = unsaturated at

o


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o 3 enymes responsible or breadown:

Adipose Triglyceride !ipase (AT!)

Hormone 0ensitive !ipase (H0!)

"onoacylglycerol !ipase ("!)

o Enymes initiate ree atty acid lu@ rom white adipose tissue to liver

o AT! removes one acyl group rom TAo 0uccessive removal (TADA"A)

o ree atty acids go through receptors on liver into liver and activated with Acyl#CoA

o TA is reormed in liver and is hydrolyed bac to ree atty acids by the 3 enymes

o ree atty acids in liver go to nucleus or gene e@pression

#Protein Coupled Geceptors:

o Activated when alpha subunit dissociates

o Eector protein is usually adenylyl cyclase

"aes cA"P rom ATp cA"P rises in response to epinephrine or glucagon

o Turn o: hydrolye TP to DP

o cA"P:

, regulatory subunits % , catalytic subunits

cA"P binds to regulatory subunitsdissociates rom

catalytic subunit catalytic subunit phosphorylates protein substrate to

activate protein (P+A)

To inactivate protein8 phosphatase

dephosphorylates protein

Hormonal Gegulation o at ;readown in Adipoytes:


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o Epinephrine increases cA"Pactivates P+Aactivates

hormone sensitive lipase

o *nsulin reverses epinephrine eectstimulates phosphatase to

inactivate H0!

Carnitine 0huttle:

o


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0teps o Q#o@idation: (or even \ carbons)

o X9H9TY (o@idation8 hydration8 o@idation8 thiolysis cleavage)

o Taes , carbons o during each cycle

o Energy is created by ormation o ADH, and


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Acetoacetate

3H;

Acetone

o , Acetyl CoA orms Acetoacetyl CoA

o "oved bac to muscles and reverted bac to , acetyl CoA

o ?sed in starvation8 brain also uses etone bodies

+etone ;odies produced e@cessively in Diabetic patients

o *nsulin decreases

o Epinephrine-lucagon increases

"ore lipolysis

"ore ree atty acid in plasma

"ore hepatic output o etone bodies

Gesult+etoacidosis


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Fatty Acid Synthesis- ,#esity- and !ancer:

Carbs and proteins in e@ess can be converted to atty acids stored as TA

atty acid synthesis occurs in liver and lactating mammary glands

o *n cytosol8 whereas beta#o@idation is in mitochondria

o rows , carbons at a time

o ATP and


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Acetyl CoA Carbo@ylase:

o Gate limiting step in atty acid synthesis

o *nactive orm: protomers

o Active: polymer

o Activated by Citrate

o

*nactivated by end product: !ong chain atty acyl CoAo orms "alonyl CoA rom Acetyl CoA (adds C9,)

o Allosterically regulates malonyl CoA

Gegulation o Acetyl CoA Carbo@ylate:

o Done by covalent regulation (phosphorylation) by A"P +inase

(A"P+)

o *nsulin activates protein phosphatase to activate acetyl CoA

carbo@ylase

o A"P+ inactivates acetyl CoA carbo@ylase

o A"P+ is increased during starvation by glucagon and

epinephrine

ormation o cytosolic acetyl CoA

o 9AA not permeable out o matri@gets converted to Citrate

o 9@aloacetate % Acetyl CoA = Citrate in mitochondrial matri@

o Citrate transporter moves citrate into cytosol

Especially when ATP levels high ater a meal

o Citrate in cytosol is reconverted bac to Acetyl CoA and 9AA

9AA!#"alatePyruvate (


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During synthesis:

o +etone groups reduced to hydro@yl groups by

biochemistry exam 1 review

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