1st SHIFTING

BIOCHEMISTRY
INTRODUCTION TO BIOCHEMISTRY, CELL & WATER – 2 points

Element   Atomic  Number   Electron  Shell  Capacity    

First:2  |  Second:8  |  Third:8  
Hydrogen   ¢   1  
Carbon   ¢¢¢¢¢¢   2  |  4  
Nitrogen   ¢¢¢¢¢¢¢   2  |  5  
Oxygen   ¢¢¢¢¢¢¢¢   2  |  6  
 
• Bond  System  
o Single  bond  –  longest  and  weakest  
o Double  bond  
o Triple  bond  –  shortest  and  strongest  
 
• Covalent  bond  –  formed  when  two  atoms  share  a  pair  of  electrons  
• Noncovalent  Interactions  
o Ionic  bond  –  purely  electrostatic  attractions  between  oppositely  charged  atoms  
§ Formed  when  two  atoms  share  a  pair  of  electrons  
§ Ex.  Na+  and  Cl-­‐  (Atomic  Number  11  and  17)  
o Hydrogen  bond  –  electropositive  hydrogen  atom  is  partially  shared  by  two  electronegative  atoms  
§ Responsible  for  thermal  property  formed  by  water  
o Van  der  waals  –  electron  cloud  around  any  nonpolar  atom  will  fluctuate,  producing  a  flickering  dipole  
§ NOT  weakened  by  water  
o Hydrophobic  forces  –  caused  by  a  pushing  of  nonpolar  surfaces  out  of  the  hydrogen  bonded  water  network  
 
Organelle  or  Fraction   Marker   Major  Functions  
Nucleus   DNA   Site  of  chromosomes  
Site  of  DNA-­‐directed  RNA  synthesis  
(transcription)  
Mitochondria   Glutamic  dehydrogenase   Citric  Acid  Cycle  
Oxidative  Phosphorylation  
Ribosomes   High  content  of  RNA   Site  of  protein  sysnthesis  (translation  of  
mRNA  into  proteins)  
Endoplasmic  Reticulum   Glucose-­‐6-­‐phosphatase   Membrane-­‐bound  ribosomes  are  a  major  
Rough  Endoplasmic  Reticulum  –  has  an   site  of  protein  synthesis  
abundance  of  ribosomes  on  surface   Synthesis  of  various  lipids  
Oxidation  of  many  xenobiotics  
(cytochrome  P450)  
Lysosomes   Acid  phosphatase   Site  of  many  hydrolases  (enzyme  
catalyzing  degradative  reactions)  
Plasma  Membrane   Na-­‐K  ATPase   Transport  of  molecules  in  and  out  of  the  
5’  nucleotidase   cell  
Intercellular  adhesion  and  communication  
Golgi  Apparatus   Galactosyl  transferase   Intracellular  sorting  of  proteins  
Glycosylation  reactions  
Sulfation  reactions  
Peroxisomes   Catalase   Degradation  of  certain  fatty  acids  and  
Uric  Acid  Oxidase   amino  acids  
Production  and  degradation  of  hydrogen  
peroxide  
Cytoskeleton   No  specific  enzyme  markers   Microfilaments,  microtubules,  and  
intermediate  filaments  
Cytosol   Lactate  dehydrogenase   Enzymes  of  glycolysis,  fatty  acid  synthesis  
 
• Subcellular  Fractionation  –  600g  x  10  minutes  |  15,000g  x  5  minutes  |  100,000g  x  60  minutes  |  300,000gm  x  2  hours  
o Increasing  speed  –  nucleus  à  mitochondria  à  microsomes  à  cytosol  
o Decreasing  speed  –  cytosol  à  microsomes  à  mitochondria  à  nucleus  

CHEMISTRY OF CARBOHYDRATES – 2 points

• Simplest  carbohydrate  is  a  triose  containing  3  carbons
o Can  contain  either  an  aldehyde  moiety  (H-­‐C=O)  or  a  ketone  moiety  (C=O)
o Ex.  Glyceraldehyde  and  Dihydroxyacetone

• Isomers
o Enantiomers  –  stereoisomers  that  are  mirror  images

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o Diastereomers  –  stereoisomers  that  are  NOT  mirror  images
o Epimers  –  diastereomers  that  differ  at  one  stereocenter
§ Ex.  Glucose  and  Galactose
o Anomers  –  stereoisomers  and  diastereomers  that  differ  in  configuration  around  the  anomeric  C
§ Ex.  α  and  β
• α  anomer  –  hydroxyl  group  trans  (opposite  side)  to  terminal  carboxyl  group
• β  anomer  –  hydroxyl  group  cis  (same  side)  to  terminal  carboxyl  group
o Conformational  isomer
§ Ex.  boat  and  chair
• Chair  conformation  –  stable  conformation  of  D-­‐glucose  because  OH  and  CH2OH  groups  are  found  
as  equatorial  bonds

Gram  Positive  (+)   Gram  Negative  (-­‐)  

Stains  purple  with  gram  stain Cannot  be  stained  with  gram  stain  
Presence  of  teichoic  acids  in  cell  walls GlcNAc  (β-­‐1,4)  MurNAc  strands  are  covalently  connected  
• Attached  to  C6  of  MurNAc thru  a  direct  amide  bond  between  the  ε  amino  group  of  Lys  
• Ribitol  and  glycerol  –  backbone  of  teichoic  acid on  one  strand  and  D-­‐Ala  of  another  strand  
• Structures  with  glycerol-­‐3-­‐phosphate  backbone  with   Single  peptidoglycan  layer  sandwiched  between  inner  and  
alternating  residues outer  bilayer  
Has  thick  peptidoglycan  layer  found  external  to  cell  
membrane
GlcNAc  (β-­‐1,4)  MurNAc  are  covalently  connected  by  a  
pentaglycine  bridge  between  the  ε  amino  group  of  Lys  on  
one  strand  and  D-­‐Ala  of  another  strand  

 
• Glycoproteins  
o Carbohydrate  modification  increases  the  half  life  of  proteins  
o Sugars  are  covalently  attached  to  protein  via  O  and  N  glycosidic  linkage  with  serine  and  asparagine,  respectively  
o Have  immunologic  property  
 
• Reducing  sugars  –  has  free  OH  group  on  the   • Non-­‐reducing  sugars  –  no  free  OH  group  on  the  
anomeric  carbon   anomeric  carbon  
o Ex.  Lactose  (galactose-­‐β-­‐1,4-­‐glucose)   o Cannot  open  to  form  an  aldehyde  or  H-­‐C=O  
o Maltose  (glucose-­‐α-­‐1,4-­‐glucose)   o Ex.  Sucrose  (glucose-­‐α-­‐1,2-­‐fructose)  
o Cellobiose  (glucose-­‐β-­‐1,4-­‐glucose)      
o Isomaltose  (glucose-­‐α-­‐1,6-­‐glucose)  
 
• Mucopolysaccharides/Glycosaminoglycans    
o Amino  sugar  +  negatively  charged  sulfate  or  carboxyl  group  (uronic  acid:  glucuronic  or  iduronic  acid)  
o Are  anionic  with  the  presence  of  uronic  acid  component  and  sulfated  groups  found  in  the  amino  sugars  
o GAGs  are  covalently  attached  to  proteins  forming  proteoglycans  
§ Hyaluronic  acid  –  for  function  of  synovial  fluid  in  joint  lubrication  
§ Keratan  sulfate  –  no  uronic  acid  component  

CHEMISTRY OF AMINO ACIDS & PROTEINS – 2 points

• All  amino  acids  have  a  chiral  carbon  except  glycine  –  no  side  chain  
• Proline  –  cyclic  structure;  considered  as  an  imino  acid  
 
• Protein  Conformation
o Primary  Structure  –  refers  to  the  order  of  the  amino  acid  in  the  peptide  chain
§ Ex.  Amino  acid  sequence  and  peptide  linkages
§ Mainly  stabilized  by  peptide  bonds
• Partial  double  bond  character
• Covalent  bond  formed  between  an  amino  group  and  a  carboxylic  group
§ Denaturation  –  loss  of  native  structure  of  proteins  caused  by  heat  and  pH;  does  not  affect  primary  
conformation  of  amino  acid
o Secondary  –  refers  to  local  three  dimensional  folding  of  the  polypeptide  chain  in  the  protein,  resulting  from  steric  
relationships  of  amino  acid  residues  that  are  close  to  one  antoher  in  the  linear  sequence
§ Structure  is  mostly  stabilized  by  hydrogen  bonding  between  the  C  and  N  terminal
§ Ex.  α  helical,  β  sheet,  collagen  helix
o Tertiary  structure  –  geometric  relationship  between  distant  segments  of  primary  structure  and  the  relationship  of  
side  chains  with  one  another  in  three-­‐dimensional  space
§ Stabilized  by  non-­‐covalent  and  covalent  bonds
o Quaternary  –  level  of  organization  present  proteins  containing  more  than  one  polypeptide  chain
§ Stabilized  by  non-­‐covalent  and  covalent  bonds

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§ Ex.  Myoglobin  and  hemoglobin

• Essential  Amino  Acids  –  PVT  TIM  HALL

o Required  dietary  intake  because  the  human  body  can  not  synthesize  them  in  adequate  amounts
o Arginine  –  essential  only  during  infancy

Ionization  Character  of  Amino  Acid  R  Groups  

Neutral    (R  group  does  NOT  ionize)   Basic   Acidic  
Glycine,  Alanine,  Valine,  Leucine,   Lysine   Glutamic  acid  
Isoleucine,  Serine,  Threonine,  Methionine,   Arginine   Aspartic  acid  
Proline,  Tryptophan,  Glutamine,   Histidine   Cysteine  
Asparagine,  Phenylalanine   Tyrosine  

Polarity/Non  Polarity  of  Amino  Acid  R  Groups  

Polar   Non-­‐polar  
Charged  at  pH  7   Uncharged  at  pH  7   Glycine,  Valine,  Leucine,  Isoleucine,  
Lysine,  Arginine,  Glutamate,  Aspartate,   Asparagine,  Glutamine,  Serine,  Threonine,   Methionine,  Phenylalanine,  Alanine,  
Histidine   Cysteine,  Tyrosine   Tryptophan,  Proline  

• Ionic  Properties  of  Amino  Acid

o Amino  acid  can  effectively  act  as  buffers  if  the  concentration  of  the  conjugate  base  is  equal  to  the  concentration  of  
the  acid  in  which  case  pKa=pH
o pK  values  –  degree  of  dissociation  of  the  α  carboxyl,  α  amino  and  R  groups;  maximum  buffering  capacity  of  an  
amino  acid
§ Neutral  amino  acids  –  2  pKs
§ Ionizable  R  groups  –  3  pK  values
§ pH  <  pI  –  basic;  amino  acid  charge  is  negative
§ pH  >  pI  –  acidic;  amino  acid  charge  is  positive
o Isoelectric  point  (pI)  –  corresponds  to  the  pH  wherein  the  amino  acid  has  a  net  charge  of  zero  and  exists  as  a  
zwitterions
§ Standard  amino  acid  exist  as  dipolar
§ Average  of  2  pk  values

CHEMISTRY OF LIPIDS – 2 points

• Lipids  constitute  the  storage  form  of  energy  in  the  human  body
• Insoluble  in  polar  solvents  –  common  property  of  all  lipids  despite  their  diverse  structure  and  functions
• Lipids  are  amphipathic  compounds
o Hydrophobic  end  –  ω  carbon
o Hydrophilic  end  –  COOH

• Double  Bond  System  of  PUFAs

o Nonconjugated  Double  Bond  System  –  double  bonds  are  interrupted  by  a  methylene  group  (-­‐CH2-­‐)
o Conjugated  Double  Bond  System  –  not  interrupted  by  a  methylene  group

• Nomenclature  of  Fatty  Acids

o Genevan  system
§ Saturated  fatty  acids  end  in  –anoic
§ Unsaturated  fatty  acids  end  in  –enoic
o ω  system  or  n  system
§ terminal  methyl  carbon  is  C1
o Delta  system
§ C  of  the  COOH  (carboxyl  group)  is  C1
Δz
§ C  x:y
• x  –  carbon  content
• y  –  number  of  double  bond
• z  –  location  of  the  double  bond

• Physical  Properties  of  Fatty  Acids

o Boiling  point  and  melting  point  increase  with  increase  in  chain  length
o The  melting  point  decrease  with  increasing  unsaturation
o Solubility  decreases  with  increase  in  chain  length
o The  higher  the  melting  points  of  the  saturated  fatty  acids  reflect  the  uniform  rod-­‐like  shape  of  their  molecules
o The  cis-­‐double  bond(s)  in  the  unsaturated  fatty  acids  introduces  a  kink  in  their  shape,  which  makes  it  more  difficult  
to  pack  their  molecules  together  in  a  stable  repeating  array  or  crystalline  lattice

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Glycerol   Ceramide  –  sphingosine  +  fatty  acid  

• α  –  saturated  fatty  acid   Sphingosine  
• β  –  unsaturated  fatty  acid   • C1  –  attachment  of  polar  head  group  (OH)  
• α’  –  phosphate  group  +  nitrogenous  base   • C2  –  fatty  acid  attachment  via  amide  bond
 
CHEMISTRY OF BIOLOGICAL MEMBRANES – 2 points
• Biological  Membranes  –  the  component  lipids  are  asymmetrically  assembled  in  the  outer  and  inner  leaflets  of  the  
membrane  
• Membranes  consist  mainly  of  lipid  and  proteins  
o Proteins  –  component  of  biological  membrane  that  functions  as  enzymes  involved  in  signal  transduction  
• Functions  of  Membrane  Proteins  
o Structural  –  attachment  to  the  cytoskeleton  and  extracellular  matrix  
o Transport  of  substances  across  membranes  
o Catalytic  
o Receptor  –  cell  to  cell  recognition  and  signal  transduction  
 
Integral  Proteins   Peripheral  Proteins  
Contains  sequences  rich  in  hydrophobic  amino  acids  which   Situated  on  the  surface  of  the  membrane  and  constitute  its  
interact  with  the  hydrophobic  hydrocarbons  of  the  lipids,   cytoskeleton  
stabilizing  the  lipid-­‐protein  complex   Can  be  removed  by  little  or  no  disruption  on  membrane  integrity  
Spans  the  entire  lipid  bilayer   Released  by  treatment  with  salt  solutions  
Loop  back  and  forth  within  the  aqueous  core  of  the  membrane   • Spectrin  –  principal  component  of  the  cytoskeleton  
Removal  requires  disruption  of  the  membrane   underlying  the  RBC  membrane  and  accounting  for  its  
• Glycophorins  -­‐  60%  carbohydrate;  single-­‐pass   biconcave  shape  and  flexibility  
transmembrane  protein   • Band  4.1  –  link  between  RBC  membrane  and  the  
• Band  3  –  anion  channel  for  tubular  channel  and   cytoskeleton  
mediates  the  exchange  of  HCO3  for  Cl  across  the  
membrane  
 
• Categories  of  Transport  Mechanisms  
o Uniporters  –  transport  one  solute  
o Symporters  –  transport  two  different  solutes  simultaneously  in  the  same  direction  
o Antiporters  –  transport  two  different  solutes  simultaneously  in  opposite  directions  
 
• Membrane  Transport  Mechanisms  
o Passive  transport  –  no  direct  input  of  energy;  down  the  concentration  gradient  
o Simple  Diffusion  
o Facilitated  Diffusion  –  energy-­‐independent;  transport  large  molecules  thru  special  channels.  Carriers  
o Active  Transport  –  requires  energy  
 
CHEMISTRY OF ENZYMES – 2 points
• Isozymes  –  enzymes  that  catalyze  the  same  reactions  but  have  different  physicochemical  properties  
• Apoenzyme  –  protein  portion  of  the  enzyme  
 
• Mechanisms  of  Enzyme  Action  
o Acid-­‐Base  Catalysis  
§ Specific  acid  base  catalysis  –  protons  and  the  hydroxyl  groups  will  come  from  water  
§ General  acid  base  catalysis  –  protons  will  come  from  amino  acid  side  chains  
o Covalent  Catalysis  
§ Formation  of  covalent  bond  

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o Proximity  and  Orientation  Effect  
§ Bringing  multiple  substrates  together,  increasing  concentration  effect  on  the  site  
o Stabilization  of  the  Transition  State  
§ Enzymes  decrease  energy  of  activation  by  reducing  the  energy  difference  between  the  substrate  and  the  
transition  state  à  decreasing  the  degree  of  randomness  or  entropy  
 
• Factors  Affecting  Enzyme  Activity  
o pH  –  hyperbola   o Substrate  concentration  –  rectangular  
o Temperature  –  hyperbola   hyperbola  –  increasing  concentration  does  
o Enzyme  concentration  –  straight  line   not  affect  reaction  rate  –  saturation  graph  
o Inhibitors  
 
• Active  Site  –  substrate  binding  site  
o A  small  area  usually  they  say  was  just  a  cleft  or  a  crevice.  
o Indentation  within  large  molecule  of  enzymes  that  will  bind  to  your  cofactors  
o Interactions  that  will  try  to  bind  and  hold  the  substrate  to  this  active  site  are  weak  interactions  like  van  der  Waals,  
hydrogen  bonds,  ionic  interactions,  electrostatic  interactions,  London  dispersion  interaction.  
o Region  which  lowers  the  free  energy  of  transition  state  à  increase  in  reaction  rate  –  Catalytic  Effect  of  Enzymes  
 
• Michaelis  Menten  Equation  
o Kinetic  parameters  that  characterize  enzymes  
§ Km  –  reflects  the  affinity  of  the  enzyme  for  
the  substrate  
§ Vmax  
o Competitive  inhibition    
§ Km  increases  while  Vmax  remains  constant  
§ Structural  analog  of  the  normal  substrate  
o Noncompetitive  inhibition  
§ Km  remains  constant  while  Vmax  decreases  
§ Presence  of  the  active  site  and  an  allosteric  
site  
 
• Lineweaver  Burk  Plot  
o Reciprocal  of  the  Michaelis  Menten  equation  
 
• Metal  ion  cofactors  
o Acts  as  Lewis  acids  in  enzymes  
o Perform  roles  in  oxidation-­‐reduction  reactions  
o Stabilize  the  active  state  of  the  enzyme  

CHEMISTRY OF COENZYMES – 2 points

• Non-­‐protein  portion  of  the  enzyme
• Heat  stable
• Low  molecular  weight  organic  substances
• Participate  in  the  enzymatic  reaction  by  accepting  and  transferring  functional  groups  from  the  substrate  to  form  the  final  
product

Coenzyme   Vitamin  Component   Reaction  

NAD+/NADP+   Nicotinic  Acid/Niacin   Oxidation-­‐reduction  
FAD/FMN   Riboflavin   Oxidation-­‐reduction  
Thiamine  Pyrophosphate   Thiamine   Carbonyl  transfer  
Coenzyme  A   Pantothenic  Acid   Acyl  transfer  
Pyridoxal  Phosphate   Pyridoxal  Phosphate   Amino  group  transfer  
Biocytin   Biotin   Carboxylation  
Tetrahydrofolic  Acid   Folic  Acid   One  carbon  group  transfer  
Cobamide  Coenzyme   Cyanocobalamin   Alkylation  

• Coenzymes  not  derive  from  vitamins

o Coenzyme  Q  (Ubiquinone)  –  oxidation-­‐reduction
o Tetrahydrobiopterin  –  oxidation-­‐reduction
o Lipoic  acid  –  acyl  groups  and  active  aldehyde  transfer

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BIOCHEMISTRY

BIOENERGETICS AND BIOLOGICAL OXIDATION – 2 points

EXERGONIC  (ΔG  <  0)   ENDERGONIC  (ΔG  >  0)   NEUTRAL  (ΔG  =  0)  
FAVORABLE   UNFAVORABLE   System  is  at  equilibrium  
Reaction  goes  to  right  spontaneously   Reaction  goes  to  left  –  non-­‐spontaneous  
Releases  energy  as  heat  -­‐  exothermic   Requires  addition  of  energy  
0
ΔG  –  standard  free  energy  change  
Energy  coupliong  –  output  from  exergonic  reaction  can  serve  as  input  of  chemical  energy  that  will  drive  endergonic  reactions  to  completion  
 
• High  Energy  Compounds  –  contain  one  or  more  high  energy  bonds  and  liberate  about  -­‐7  to  -­‐15  kcal/mole;  participate  in  the  
flow  of  cellular  energy
o Phosphoenolpyruvate o Creatine  Phosphate
o Carbamoyl  Phosphate o ATP  à  ADP  +  Pi –  principal  energy  currency  
o 1,3,-­‐Bisphosphoglycerate of  the  cell

• Two  types  of  ATP  Synthesis

o Substrate-­‐level  Phosphorylation  –  occurs  thru  direct  cleavage  of  high  energy  bonds,  coupled  to  synthesis  of  ATP  
from  ADP  and  Pi
§ Produces  a  P/O  ratio  of  2:1
o Oxidative  phosphorylation  –  occurs  thru  coupling  oxidation  of  substrates  in  the  electron  transport  chain  with  
phosphorylation  of  ADP
§ Culmination  of  energy  yielding  metabolism  in  aerobic  organisms
§ Involves  the  reduction  of  oxygen  to  water  with  electrons  donated  by  NADH  and  FADH2
§ Takes  place  in  the  electron  transport  chain
§ Produces  a  P/O  ratio  of  3:1  via  Complex  I

• ATP  Synthesis/Mitchell’s  Chemiosmotic  Model  –  driving  force  that  allows  coupling  of  phosphorylation  with  oxidation  of  a  
substance  in  the  Respiratory  Chain  is  the  proton  gradient  created  between  the  matrix  and  the  intermembranous  space  of  
the  mitochondria  –  proton  motive  force  –  drives  the  synthesis  of  ATP  as  protons  flow  passively  back  into  matrix  thru  a  
proton  pore  associated  with  ATP  synthase
o Mitochondria
§ Matrix  –  contains  the  pyruvate  dehydrogenase
§ Outer  membrane  –  permeable  to  all  molecules  and  ions
§ Inner  membrane  –  impermeable  to  most  ions  even  protons  and  H  atoms;  energy  trapping  mechanism;
site  of  Respiratory  Chain  system

• Electron  Transport  Chain

o Complex  I:  NADH  to  Ubiquinone
o Complex  II:  Succinate  to  Ubiquinone
o Complex  III:  Ubiquinone  to  Cytochrome  C
o Complex  IV:  Cytochrome  C  to  O2
o Complex  V:  ATP  Synthase

• Energy  Yield  from  the  Electron  Transport  Chain  –  moles  of  ATP  synthesized  for  every  atom  of  oxygen  consumed
o NADH  –  P/O  ratio  of  3:1
o FADH2  –  P/O  ratio  of  2:1  

AGENTS  THAT  INTERFERE  WITH  OXIDATIVE  PHOSPHORYLATION  

Type  of  interference   Compound   Target/Mode  of  Action  
Inhibition  of  electron  transfer   Cyanide   Inhibiting  the  reduction  of  Fe  of  
Carbon  monoxide   cytochrome  oxidase  
 
Antimycin  A   Blocks  electron  transfer  from  cytochrome  
b  to  cytochrome  c1  (Complex  III)  
Myxothiazol   Prevent  electron  transfer  Fe-­‐S  center  to  
Rotenone   ubiquinone  (Complex  I)  
Amytal  
Ptericidin  A  
DCMU   Competes  with  Qb  for  binding  site  in  PSII  
Inhibition  of  ATP  Synthase   Aurovertin   Inhibits  F1  
Oligomycin   Inhibit  F0  and  CF0  
Venturicidin   No  ATP  synthesis  can  occur  
DCCD   Blocks  proton  flow  thru  F0  and  CF0  
Uncoupling  of  phosphorylation  from   FCCP   Hydrophobic  proton  carriers  
electron  transfer   DNP   No  oxidative  phosphorylation  
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Valinomycin   K  ionophore  –  allows  flowing  back  of  K  
ions  
Thermogenin   In  brown  fat,  forms  proton-­‐conducting  
pores  in  inner  mitochondrial  membrane  
Inhibtion  of  ATP-­‐ADP  exchange   Atractyloside   Inhibits  adenine  nucleotide  translocase  
ATP  synthesis  will  stop  

INTRODUCTION TO METABOLISM – 1 point

• TCA  Cycle  –  amphibolic  cycle
o Serves  as  the  final  common  oxidative  pathway  for  carbohydrates,  proteins  and  fats  –  catabolic  part  of  the  cycle
o Involves  the  production  of  reducing  equivalents  that  will  enter  the  ETC  for  ATP  production
o For  gluconeogenesis  thru  the  intermediates  of  the  TCA  cycle

• Low  Energy  Charge  will  stimulate  the  following   • High  Energy  of  the  Cell  will  stimulate  the  ff.  
pathways pathways
o Glycolysis o Gluconeogenesis
o Glycogenolysis o Glycolysis
o Fatty  acid  oxidation o Fatty  acid  degradation

MEMBRANE RECEPTORS & SIGNAL TRANSDUCTION – 1 point

• General  Scheme  
o A  ligand  or  a  hormone  will  bind  to  a  specific  receptor  –  either  the  receptor  is  bound  inside  the  cell  or  expressed  on  
the  membrane  forming  a  hormone-­‐receptor  complex.  
o The  hormone-­‐receptor  complex  will  stimulate  a  transducer  molecule  
o The  transducer  molecule  will  transfer  the  message  from  the  ligand  inside  the  cell  
o Active  transducer  molecule  will  in  turn  activate  effector  proteins  (enzymes)  –  ex.  adenylyl  cylase,  phospholipase  C  
nd
o Formation  of  your  2  messengers  will  stimulate  signalling  proteins  that  in  effect  will  promote  
§ Ion  transport  
§ Stimulate  or  inhibit  metabolic  pathways  
§ Gene  expression  –  formation  of  new  protein  molecules  involving  the  process  of  transcription  and  
translation  
§ Cell  movement  
 
• Intercellular  Signal  Transduction  
o Juxtacrine  or  Contact-­‐dependent  –  type  of  contact  that  transfers  molecules  directly  to  a  nearby  cell.  
o Paracrine  –  a  particular  cell  synthesize  ligands  and  adjacent  cells  which  possess  specific  receptors  will  be  able  to  
bind  and  react  on  those  ligands  
o Autocrine  –  a  particular  cell  synthesize  and  possess  its  own  receptor  for  the  particular  ligand  
o Synaptic  or  Neuronal  signaling  –  involves  a  neuron  to  its  axon  to  be  able  to  transmit  the  impulse  to  another  cell  
through  neuromuscular  junction  
o Endocrine  –  a  particular  cell  after  synthesizing  the  ligand  will  secrete  the  molecule  into  the  circulation  sending  it  
into  faraway  cells  or  tissues  where  the  cells  possessing  the  specific  receptor  will  bind  and  react  on  the  ligand.  
§ Ex.  glucagon,  epinephrine,  insulin.  

  cAMP   cGMP   IP3/DAG  

G-­‐protein  type   Gs  or  Gi   Gt   Gq  
Primary  Effector   Adenylyl  Cyclase   Phosphodiesterase   Phospholipase  C  
Protein  Kinase   PKA   PKG   PKC  
Ca  dependent  kinase  

• G-­‐protein  coupled  receptors

o Has  7  α  helices  that  crosses  the  membrane  –  also  known  as  serpentine,  heptahelical,  7  transmembrane  helices
o Ex.  β  adrenergic  receptors  –  epinephrine  and  phrenillin
• Tyrosine  Kinase
o Extracellular  domains:  cysteine-­‐rich,  immunoglobulin-­‐like,  fibronectin-­‐type  III  like  domain
o Cytosolic  domains:  tyrosine  kinase  domain,  kinase  insert  region
• Covalent  Modification
o Attachment  or  removal  of  a  specific  group  from  the  enzyme  thru  formation  or  cleavage  of  covalent  bonds
o Attachment  or  removal  of  a  phosphate  group  –  most  common  form  of  covalent  modification  affecting  activity  of  
the  enzyme

BIOCHEMISTRY OF HORMONES – 2 points

• Peptide  Hormones    
o Independent  of  carrier  proteins  for  their  transport  
o Thyroid  hormones  as  well  as  catecholamines  are  derived  from  tyrosine  

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o Polypeptides  are  synthesized  like  other  proteins    from  amino  acids  by  a  process  that  requires  mRNA  and  occurs  in  
ribosomes  
o Encoded  by  a  single  gene  
 
HORMONES  THAT  REGULATE  FUEL  METABOLISM  
Anabolic  Hormones   Counterregulatory  Hormones  
Insulin   Glucagon,  Epinephrine,  Thyroid  Hormone,  Norepinephrine  
Insulin-­‐related  peptides   Cortisol,  Somatostatin,  Growth  hormone  
Glucagon  –  potent  counter-­‐regulatory  hormone  that  stimulates   Insulin  –  major  anabolic  hormone;  stimulates  glycolysis;  GLUT  
gluconeogenesis   translocation;  promotes  entry  of  glucose  into  skeletal  muscles  and  
lipogenesis  in  adipose  cells  

• Insulin  
o Polypeptide  composed  of  2  chains,  A  and  B  linked  by  2  interchain  and  intrachain  disulfide  bridges  
o Conserved  positions  constitute  a  composite  active  region  are  the:  
§ 3  disulfide  bonds  
§ hydrophobic  residues  in  the  carboxyl  terminals  of  the  B  chain  
§ amino  and  carboxy  terminals  of  the  A  chain  
o Synthesis:  cleavage  of  leader  sequence  results  in  the  formation  of  proinsulin  which  provides  the  conformation  
necessary  for  the  proper  disulfide  bridges  
§ Composed  of  B&A  chains  linked  by  a  connecting  C  peptide  
§ C-­‐peptide  –  no  known  biologic  activity  
 
HORMONAL  CONTROL  
INSULIN   • Anabolic  hormone  
• For  protein  synthesis  
• Stimulus:  hyperglycemia  –  to  lower  blood  glucose  levels  
• Stimulates  glycolysis  to  lower  blood  glucose  levels  for  utilization  of  energy  
• Favors  glycogen  synthesis  
• Favors  the  non-­‐phosphorylated  form  of  the  enzyme  
• Favors  lipogenesis  over  lipolysis  
• Promotes  induction  of  glucokinase  
• Prevails  in  the  well-­‐fed  state  –  amino  acids  is  now  directed  to  protein  synthesis  in  the  liver  
GLUCAGON   • Proteolysis  –  breakdown  of  proteins  to  form  amino  acids  
• Stimulus:  hypoglycemia  –  to  elevate  blood  glucose  levels  
• Favors  gluconeogenesis  &  glycogenolysis  in  order  to  produce  glucose  
• Favors  the  phosphorylated  form  of  the  enzyme  
• Favors  lipolysis  to  mobilized  the  triacylglycerol  in  the  adipose  tissue  and  use  it  as  a  form  of  energy  
 
CHEMISTRY OF STEROID HORMONES – 2 points
• All  steroid  hormones  are  synthesized  from  cholesterol
• Structure  of  Steroid  Hormones
o Based  on  the  number  of  carbon  atoms  they  possess
§ Pregnane  derivatives
• Contain  21  carbons  (6  from  side  chains)
• Includes  the  progestins  and  corticosteroids
§ Androstane  derivatives
• Contains  19  carbons  (no  side  chain  in  C17)
• Includes  the  androgens
§ Estrane  derivatives
• Contains  18  carbons  (no  methyl  group  at  C10  –  aromatic  ring  A)
• Includes  the  estrogens

o Structural  features  that  are  relevant  for  the  biosynthetic  pathways

§ Steroid  nucleus  of  cholesterol  remains  intact
§ Hydroxyl  group  at  C2  is  always  inherited  from  the  parent  compound
§ Side-­‐chains  is  reduced  at  C17  –  shortened  to  two  in  progestins  and  corticosteroids
§ C3  hydroxyl  group  is  inherited  from  cholesterol  but  the  other  oxygen  functions  have  to  be  introduced  by  
hydroxylation  reactions
§ Estrogens  are  distinguished  by  the  aromatic  nature  of  ring  A

• Synthesis  of  Adrenal  Steroids

o OH  to  C21  –  50%  mineralocorticoid,  50%  glucocorticoid  property
o OH  to  C17  –  75%  glucocorticoid  property,  25%  mineralocorticoid  property
o OH  (aldehyde)  to  C18  –  100%  mineralocorticoid  property

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• Glucocorticoids
o Cortisol  –  predominant  glucocorticoid  in  humans  and  it  is  made  in  the  zona  fasciculata  of  the  adrenal  cortex
§ Addison’s  Disease
• Also  known  as  Primary  Adrenal  Insufficiency
• Increased  pigmentation  of  skin  –  MSH  –  POMC  gene
§ Secondary  Adrenal  insufficiency
• Similar  to  Addison’s  disease  but  without  hyperpigmentation  
• No  problem  in  the  adrenal  cortex
§ Cushing  syndrome
• Disorder  of  glucocorticoid  excess

• Mineralocorticoids
o Aldosterone  –  most  potent  hormone  and  made  exclusively  in  the  zona  glomerulosa
§ Primary  Aldosteronism
• Classic  manifestations  of  hypertension,  hypernatremia,  hypokalemia  and  alkalosis
• Suppressed  levels  of  renin  and  angiotensin  II
§ Secondary  aldosteronism
• Resembles  the  primary  form  except  for  elevated  renin  and  angiotensin  II  levels

• Androgens
o Testosterone  –  formed  in  testis  (male)
o Androstenedione  –  formed  in  the  adrenals  (both  male  and  female)
o Testosterone  and  Androstenedione  –  formed  in  theca  cells  of  the  ovary  (female)

• Estrogens
o Testis  (male)  –  testosterone  is  converted  to  estradiol
o Peripheral  tissues  (male)  –  androstenedione  is  converted  to  estrone
o Ovary  (female)  –  estradiol(E2)  is  the  major  form  of  estrogen  from  the  ovaries
o Peripheral  tissues  (female)
§ Adrenals  –  androstenedione  à  estrone  à  estradiol
§ Adipose,  liver,  skin  –  androstenedione  is  converted  to  estrone
§ Estrone  –  major  form  of  estrogen  in  post-­‐menopausal  women

DIGESTION OF CARBOHYDRATES – 1 point

• Glycosidases  –  enzymes  that  hydrolyze  glycosidic  bonds
• Oral  phase  –  mouth  
o Salivary  amylase  (ptyalin)  –  cleave  internal  α(1à4)  bonds  
§ Optimum  pH  is  from  6.6  to  6.8  
§ Requires  calcium  and  chloride  ions  as  cofactors  
• Gastric  phase  –  stomach  
• Pancreatic  phase  –  duodenum  
o Pancreatic  amylase  –  same  action  and  optimum  conditions  as  salivary  amylase  
§ Has  an  absolute  requirement  for  chloride  ions  
• Intestinal  phase  –  intestinal  brush  border  
o Sucrase-­‐isomaltase  complex  –  accounts  for  80%  of  the  maltase  activity  in  the  intestine  
o Glucoamylase  –  hydrolyze  external  α(1à4)  bonds  –  exoglucosidase  
o Lactase  or  β-­‐glycosidase  –  specific  for  β(1à4)  
o Trehalase  –  cuts  α(1à1)  linkages  
o Dietary  fibers  remain  undigested  because  of  the  absence  of  β(1à4)  glycosidase  in  humans  
 
DIGESTION OF PROTEINS – 1 point
 
Enzyme   Zymogen   Size  of  fragment   Means  of  activation   Specificity  
removed  during  
activation  
Gastric  (Optimum  pH  1.5  to  2.5)  
Pepsin   Pepsinogen   42-­‐44  amino  acid   HCl  and  pepsin   Phe,  Tyr,  Glu,  Asp  
peptide  
Pancreatic  Proteases  (Optimum  pH  7.5  to  8.5)  
Trypsin   Trypsinogen   Hexapeptide   Enterokinase   Arg,  Lys  
(enteropeptidase)  and  
trypsin  
Chymotrypsin   Chymotrypsinogen   Two  dipeptides,   trypsin   Aromatic  amino  acids  
creating  a  three  subunit   (Phe,  Tyr,  Trp)  and  Leu,  
enzyme   Met  
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Elastase   Proelastase   Decapeptide   trypsin   Ala,  Gly,  Ser  
Carboxypeptidase  A   Procarboxypeptidase  A     trypsin   C-­‐terminal  peptide  
bonds  of  Val,  Leu,  Ile,  
Ala  
Carboxypeptidase  B   Procarboxypeptidase  B     trypsin   C-­‐terminal  peptide  of  
basic  amino  acids  (Arg,  
Lys)  
Intestinal  proteases  (Optimum  pH  7.5  to  8.5)  
Aminopeptidase         N-­‐terminal  peptide  
Dipeptidase         Dipeptides  and  
tripeptides  

DIGESTION OF LIPIDS – 1 point

• Pancreatic  Lipase  –  major  enzyme  that  digests  dietary  triacylglycerols  

o Hydrolyzes  fatty  acids  of  all  chain  lengths  from  positions  1  and  3  of  the  glycerol  moiety  of  triacylglycerols  
producing  2  free  fatty  acids  and  2-­‐monoacylglycerol  

CAG 10