Respirasi

 sel  dan  Metabolit  

sekunder  
Hydrogen  carriers  such  as  NAD+  shu@le  
electrons  in  redox  reacBons  
•  Enzymes  remove  electrons  from  glucose  
molecules  and  transfer  them  to  a  coenzyme  

OXIDATION

Dehydrogenase
and NAD+

REDUCTION

Figure 6.5
Redox  reacBons  release  energy  when  electrons  
“fall”  from  a  hydrogen  carrier  to  oxygen  
•  NADH  delivers  electrons  to  a  series  of  electron  
carriers  in  an  electron  transport  chain  
–  As  electrons  move  from  carrier  to  carrier,  their  
energy  is  released  in  small  quanBBes    

Ener
g
avai y releas
lable e
for m d and n
akin ow
g AT
P

E
of th LECTRO
e ele N
ctro CARR Electron flow
n tra IE
nspo RS
rt ch
Figure 6.6
ain
Two  mechanisms  generate  ATP  
•  Cells  use  the  energy   High H+
concentration

released  by  “falling”   ATP synthase

uses gradient

electrons  to  pump  H Membrane

energy to
make ATP
+  ions  across  a  
Electron
membrane   transport
chain

–  The  energy  of  the  

ATP
gradient  is   synthase

harnessed  to  make  

ATP  by  the  process  
Energy from

of  chemiosmosis     Low H+
concentration

Figure 6.7A
•  ATP  can  also  be  
made  by  
transferring  
phosphate  groups  
Enzyme

from  organic  
molecules  to  ADP   Adenosine

Organic molecule
(substrate)
– This process
is called
Adenosine
substrate-level
phosphorylation New organic molecule
(product)

Figure 6.7B
STAGES OF CELLULAR RESPIRATION AND
FERMENTATION
Overview:  RespiraBon  occurs  in  three  
main  stages  
•  Glycolysis  (breaks  down  glucose  into  two  
molecules  of  pyruvate)    
•  The  citric  acid  cycle  (completes  the  breakdown  
of  glucose)    
•  Oxida0ve  phosphoryla0on  (accounts  for  most  
of  the  ATP  synthesis)    
 •  An  overview  of  cellular  respiraBon  

High-energy electrons
carried by NADH

GLYCOLYSIS ELECTRON
KREBS
Glucose Pyruvic TRANSPORT CHAIN
CYCLE
acid AND CHEMIOSMOSIS

Cytoplasmic
fluid Mitochondrion

Figure 6.8
Glycolysis  harvests  chemical  energy  by  
oxidizing  glucose  to  pyruvic  acid    

Glucose Pyruvic
acid

Figure 6.9A
 PREPARATORY
Steps – A fuel Glucose PHASE
Step
•  Details  of  
molecule is energized, (energy investment)
using ATP.
Glucose-6-phosphate

glycolysis   Fructose-6-phosphate

Fructose-1,6-diphosphate
Step A six-carbon
intermediate splits into
two three-carbon Glyceraldehyde-3-phosphate
intermediates. (G3P)

ENERGY PAYOFF
Step A redox PHASE
reaction generates
NADH. 1,3-Diphosphoglyceric acid
(2 molecules)

Steps – ATP 3-Phosphoglyceric acid

and pyruvic acid (2 molecules)
are produced.
2-Phosphoglyceric acid
(2 molecules)

2-Phosphoglyceric acid
(2 molecules)

Pyruvic acid
Figure 6.9B (2 molecules
per glucose molecule)
Pyruvic  acid  is  chemically  groomed  for  
the  Krebs  cycle  
•  Each  pyruvic  acid  molecule  is  broken  down  to  
form  CO2  and  a  two-­‐carbon  acetyl  group,  which  
enters  the  Krebs  cycle  

Pyruvic Acetyl CoA

acid (acetyl coenzyme A)

CO2
Figure 6.10
The  Krebs  cycle  completes  the  oxidaBon  of  organic  
fuel,  generaBng  many  NADH  and  FADH2  molecules  
Acetyl CoA
•  The  Krebs  cycle  
is  a  series  of  
reacBons  in  
which  enzymes  
strip  away   KREBS 2

electrons  and  H CYCLE CO2

+  from  each  

acetyl  group  

Figure 6.11A
 2 carbons enter cycle
Oxaloacetic
acid 1

Citric acid

5 CO2 leaves cycle

KREBS 2
CYCLE

Malic
acid

4
Alpha-ketoglutaric acid
3
CO2 leaves cycle
Succinic
acid

Step Steps and Steps and

Acetyl CoA stokes NADH, ATP, and CO2 are generated Redox reactions generate FADH2
the furnace during redox reactions. and NADH.

Figure 6.11B
Chemiosmosis  powers  most  ATP  
producBon  
•  The  electrons  from  NADH  and  FADH2  travel  
down  the  electron  transport  chain  to  oxygen    
•  Energy  released  by  the  electrons  is  used  to  
pump  H+  into  the  space  between  the  
mitochondrial  membranes  
•  In  chemiosmosis,  the  H+  ions  diffuse  back  
through  the  inner  membrane  through  ATP  
synthase  complexes,  which  capture  the  energy  
to  make  ATP  
Figure 9.15

Intermembrane H
space H

Protein H
complex H
Cyt c
of electron
carriers
IV
Q
III
I
ATP
II synth-
2 H + 1/2O2 H2O ase
FADH2 FAD

NADH NAD
ADP Pi ATP
(carrying electrons
from food) H
Mitochondrial
matrix
1 Electron transport chain 2 Chemiosmosis
Oxidative phosphorylation
Certain  poisons  interrupt  criBcal  events  in  
cellular  respiraBon  
Rotenone Cyanide, Oligomycin
carbon monoxide

ELECTRON TRANSPORT CHAIN ATP SYNTHASE

Figure 6.13
Herbicide  Mechanism  AcBon  
 6.14    Review:  Each  molecule  of  glucose  
yields  many  molecules  of  ATP  
•  For  each  glucose  molecule  that  enters  cellular  
respiraBon,  chemiosmosis  produces  up  to  38  
ATP  molecules    
Cytoplasmic Mitochondrion
fluid
Electron shuttle
across
membranes

KREBS
GLYCOLYSIS
2
2 KREBS CYCLE
ELECTRON
Glucose Acetyl CYCLE TRANSPORT CHAIN
Pyruvic CoA AND CHEMIOSMOSIS
acid

by substrate-level used for shuttling electrons by substrate-level by chemiosmotic

phosphorylation from NADH made in glycolysis phosphorylation phosphorylation

Maximum per glucose:

Figure 6.14
 6.15    FermentaBon  is  an  anaerobic  
alternaBve  to  aerobic  respiraBon  
•  Under  anaerobic  condiBons,  many  kinds  of  cells  
can  use  glycolysis  alone  to  produce  small  
amounts  of  ATP    
–  But  a  cell  must  have  a  way  of  replenishing  NAD+  
 •  In  alcoholic  fermentaBon,  pyruvic  acid  is  
converted  to  CO2  and  ethanol  
– This recycles NAD+ to keep glycolysis working

released

GLYCOLYSIS

2 Pyruvic 2 Ethanol
Glucose acid

Figure 6.15A Figure 6.15C

 •  In  lacBc  acid  fermentaBon,  pyruvic  acid  is  
converted  to  lacBc  acid  
– As in alcoholic fermentation, NAD+ is recycled

•  Lactic acid fermentation is used to make cheese

and yogurt

GLYCOLYSIS

2 Pyruvic 2 Lactic acid

acid
Glucose

Figure 6.15B
Cells  use  many  kinds  of  organic  
molecules  as  fuel  for  cellular  respiraBon  
•  Polysaccharides  can  be  hydrolyzed  to  
monosaccharides  and  then  converted  to  glucose  
for  glycolysis  
•  Proteins  can  be  digested  to  amino  acids,  which  
are  chemically  altered  and  then  used  in  the  
Krebs  cycle  
•  Fats  are  broken  up  and  fed  into  glycolysis  and  
the  Krebs  cycle  
•  Pathways  of  molecular  breakdown  

Food, such as
peanuts

Polysaccharides Fats Proteins

Sugars Glycerol Fatty acids Amino acids

Amino
groups

Pyruvic ELECTRON
Glucose G3P Acetyl KREBS
acid TRANSPORT CHAIN
CoA CYCLE
AND CHEMIOSMOSIS
GLYCOLYSIS

Figure 6.16
Food  molecules  provide  raw  materials  
for  biosynthesis  
•  In  addiBon  to  energy,  cells  need  raw  materials  
for  growth  and  repair  
–  Some  are  obtained  directly  from  food  
–  Others  are  made  from  intermediates  in  glycolysis  
and  the  Krebs  cycle  
•  Biosynthesis  consumes  ATP    
•  Biosynthesis  of  macromolecules  from  
intermediates  in  cellular  respiraBon  
ATP needed to
drive biosynthesis

GLUCOSE SYNTHESIS
KREBS Acetyl Pyruvic
G3P Glucose
CYCLE CoA acid

Amino
groups
Amino acids Fatty acids Glycerol Sugars

Proteins Fats Polyscaccharides

Cells, tissues, organisms

Figure 6.17
Classes  of  phytochemicals  with  
medicinal  properBes  
•  Plants produce
>200.000
compounds
•  Many of these
chemicals function
in defense
 Three structural classes of
specialized metabolites
Phenolic: e.g. Flavonoids; Salicylic acid; Lignins etc

Although  hugely  diverse,  

Coumarins
specialized  metabolites  
are  derived  from  a  few  
dozen  highly  versaBle   Carbohydrate
metabolism
s
central  intermediates,   Glycosinolate
which  are  modified  in  lots  
Photo-
of  different  ways   synthesis

Terpenoids:
Alkaloids e.g. Limonoids
Alkaloids
Saponins
Pinene
Redrawn from Hartmann, T. (1996). Diversity and variability of plant secondary
metabolism: a mechanistic view. Entomologia Experimentalis et Applicata 80: 177-188.
 Alkaloids are biosynthetically diverse;
most derive from amino acids
There are
approximately 2500
benzylisoquinoline
alkaloids (BIAs),
including morphine
Tropane alkaloids
include cocaine

Senecionine is
a pyrrolizidine The ~2000
monterpenoid
alkaloid
indole alkaloids
Caffeine is a (MIAs) are derived
purine alkaloid from strictosidine
Monoterpenoid indole alkaloids (MIAs)
are derived from strictosidine
Rauwolfia
serpentina

MIAs are mainly known from two

plants “Indian snakeroot” aka
Sarpagandha, and Madagascar
periwinkle

Catharanthus
roseus

Reprinted from Loris, E.A., Panjikar, S., Ruppert, M., Barleben, L., Unger, M., Schübel, H. and Stöckigt, J. (2007). Structure-based engineering of strictosidine
synthase: Auxiliary for alkaloid libraries. Chem. Biol. 14: 979-985 with permission from Elsevier; Forest and Kim Starr; Vinayaraj
Benzylisoquinoline alkaloids (BIAs)
share a benzylisoqunoline structure
Benzylisoquinoline alkaloids (BIAs) are a
family of about 2500 compounds that are
all based on the elaboration of a simple
skeletal structure

Noscapine
Cough suppressant from
Papaver somniferum
Reprinted from Liscombe, D.K., MacLeod, B.P., Loukanina, N., Nandi, O.I. and Facchini, P.J. (2005). Evidence for the monophyletic evolution of
benzylisoquinoline alkaloid biosynthesis in angiosperms. Phytochemistry. 66: 1374-1393 with permission from Elsevier; Richard Old, XID Services, Inc.
 Alkaloids contain nitrogen and include
stimulants and narcotics
Catharanthus Coffee
roseus
Coca
Caffeine
Cocaine

Vincris0ne  

Nicotine

Morphine
Papaver somniferum
Nicotiana tabacum
 Terpenoids are diverse compounds
derived from isoprene units
Limonene, a Many  low-­‐
monoterpene (C10) Farnesol, a molecular  weight  
sesquiterpene terpenoids  are  
Isoprene   volaBle,  and  
Isoprene (C5) (C15)
components  of  
essenBal  oils  

Linalool

Pinene Eucalyptol

Image sources: Calvero; Wilhelm Thomé; Forest & Kim Starr; Karan A. Rawlins, University of Georgia
 Terpenoids are diverse compounds
derived from isoprene units
Artemisinin Tetrahydro-
cannabinol (THC)

Artemisia Cannibus
annua sativa

Taxol

Ginkgo Panax
biloba ginseng
Taxus breviola

Ginkgolide Ginsenoside
Photo credit: Dave Powell, USDA Forest Service, Bugwood.org
 Phenolics: flavonoids, anthocyanins
and related compounds
Syzygium aromaticum

Genistein an
isoflavonoid
from soy beans
Eugenol
Tannins Found in
Epigallocatechin  gallate   tea, wine, nuts and
(EGCG),  a  flavonoid  from  green   many plants
tea  

Curcumin from the spice turmeric

Brian Arthur
 Most plant phenolics are products
of phenylpropanoid metabolism

Phenylalanine

Gingerol

Vitis Cyanidin-glucoside
Zingiber vinifera
officinale
From: Buchanan, B.B., Gruissem, W. and Jones, R.L. (2000) Biochemistry and Molecular Biology of Plants. American Society of Plant Physiologists.
 Bioprospecting: Drugs and
medicines found by plant screening

Chemical assays
Plant samples
are collected and
extracted

Biological
assays

Heydrienne; Jim Gathany, CDC image 7282;

 Collecting and selecting plants to
Random collecting screen
By family - Certain
plant families, such
as Papaveraceae
are rich in medicinal
compounds

With indigenous guides

Zoopharmacognosy – many
animals have been observed to
self-medicate by eating
pharmacologically active plants

Reprinted by permission from Macmillan Publishers Ltd from Dalton, R. (2000). Political uncertainty halts bioprospecting in Mexico. Nature. 408: 278-278; Manfred Mielke USDA; Poppy photos by Forest and Kim Starr; Bonobo by Kabir Bakie
Medicinal compounds are unequally
distributed in plant families
Plant  families  associated  with  drug-­‐
producBon  are  indicated  in  green,  and  
red  indicates  families  with  endangered  
species  

Myrtaceae
(eucalyptus, clove)

Apocynaceae (periwinkle)

Solanaceae (tobacco,
Taxaceae
nightshade, peppers) Papavaraceae
(Pacific yew)
(poppy)
Zhu, F., Qin, C., Tao, L., Liu, X., Shi, Z., Ma, X., Jia, J., Tan, Y., Cui, C., Lin, J., Tan, C., Jiang, Y. and Chen, Y. (2011). Clustered patterns
of species origins of nature-derived drugs and clues for future bioprospecting. Proc. Natl. Acad. Sci. 108: 12943-12948.
Guilt by association – drug discovery
by relatedness
Some plant families are more likely to have medicinal value. Plant
genera used medicinally in three indigenous cultures were mapped, and
some overlaps identified; good candidates for further study!

Saslis-Lagoudakis, C.H., Savolainen, V., Williamson, E.M., Forest, F., Wagstaff, S.J., Baral, S.R., Watson, M.F., Pendry, C.A. and Hawkins, J.A. (2012). Phylogenies reveal predictive
power of traditional medicine in bioprospecting. Proc. Natl. Acad. Sci. 109: 15835–15840. See also Zhu, F., Qin, C., Tao, L., Liu, X., Shi, Z., Ma, X., Jia, J., Tan, Y., Cui, C., Lin, J.,
Tan, C., Jiang, Y. and Chen, Y. (2011). Clustered patterns of species origins of nature-derived drugs and clues for future bioprospecting. Proc. Natl. Acad. Sci. 108: 12943-12948.