Download Aerobic metabolism

Aerobic metabolism
- CC,RCH,ATP,PDH,β
β-oxidation,ketone bodies –
Energy-53
Vladimíra Kvasnicová
Respiratory chain (RCH)
•
is found in all cells containing mitochondria
•
is composed of 4 enzyme complexes
•
the enzymes occur in the inner mitochondrial
membrane
•
RCH oxidizes NADH+H+ to NAD+ and FADH2 to
FAD → electrons are transported to O2
•
protons (H+) are transported to the
intermembrane space ⇒ proton gradient
Recommended animations
• electron transport chain
http://vcell.ndsu.nodak.edu/animations/etc/index.htm
• ATP synthesis
http://vcell.ndsu.nodak.edu/animations/atpgradient/i
ndex.htm
for animations see
respiratory chain, ATP synthesis
The figure is found at http://plaza.ufl.edu/tmullins/BCH3023/cell%20respiration.html (December 2006)
↑ reducing
properties
Gibbs
energy
„G“
Redox
potential
„E“
↑ oxidizing
properties
The figure is found at http://www.grossmont.net/cmilgrim/Bio220/Outline/ECB2Figures&Tables_Ed2Ed1/Chapter14_13/REDOX_POTENTIALS_ElectronTransportChain_Fig14-21.htm (December 2006)
The figure is found at http://academic.brooklyn.cuny.edu/biology/bio4fv/page/mito_ox.htm (December 2006)
Citrate cycle
succinate DH
The figure is found at http://www.cellml.org/examples/images/metabolic_models/the_electron_transport_chain.gif (December 2006)
Complex II can not transport H+
FADH2
The figure is found at http://web.indstate.edu/thcme/mwking/oxidative-phosphorylation.html (December 2006)
inner mitochondrial
membrane
ATP synthase
The figure is found at http://plaza.ufl.edu/tmullins/BCH3023/cell%20respiration.html (December 2006)
Uncoupling
proteins
(UCP)
= separate
RCH from ATP
synthesis
(the synthesis is
interrupted)
energy from H+
gradient is released
as a heat
The figure is found at http://departments.oxy.edu/biology/Franck/Bio222/Lectures/March23_lecture_shuttles.htm (December 2006)
Synthesis of ATP in cells is called
1. oxidative phosphorylation
alternative
names
aerobic phosphorylation
2. substrate level phosphorylation
(= formation of ATP without direct presence of oxygen;
energy source for this ATP synthesis is an energy rich
compound: 1,3-bisphosphoglycerate – 1,3-BPG,
phosphoenolpyruvate - PEP, succinyl-CoA, GTP, creatine
phosphate,...)
ATP (GTP) can be formed in these
reactions
•
1,3-BPG + ADP → 3-phosphoglycerate + ATP (in glycolysis)
•
PEP + ADP → pyruvate + ATP (in glycolysis)
•
succinyl~CoA + GDP+Pi → succinate + GTP (in Krebs cycle)
•
GTP + ADP → GDP + ATP
•
creatine phosphate + ADP → creatine + ATP (in muscles)
creatine kinase (CK)
•
ADP + ADP → ATP + AMP
(adenylate kinase = myokinase)
Adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2
Oxidative metabolism in mitochondria
• pyruvate dehydrogenase (PDH)
glucose, amino acids
• glutamate dehydrogenase (GMD)
amino acids
• β-oxidation of fatty acids
fatty acids
• ketone bodies degradation
ketone bodies
• Krebs cycle
all nutrients
• respiratory chain – O2
NADH, FADH2
• oxidative phosphorylation
= ATP synthesis in cooperation with respiratory chain
2-oxoacid dehydrogenase is a multienzyme complex
mitochondria
„pyruvate
dehydrogenase
reaction“ = PDH
= oxidative decarboxylation of pyruvate
The figure is found at: http://faculty.uca.edu/~johnc/pdhrxns.gif (December 2006)
GLUTAMATE DEHYDROGENASE
- oxidative deamination of glutamate removes amino group from carbon sceleton of Glu in the liver
1. –NH2 from AAs was transfered by transamination ⇒ Glu
2. free ammonia is released by oxidative deamination of Glu
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
β-oxidation of fatty acids
(1 cycle)
The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)
cytoplasm
Transport of
fatty acids into
a mitochondrion
CARNITIN
TRANSPORTER
The figure was accepted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
Ketone bodies degradation
(oxidation)
proceeds during starvation
in extrahepatic tissues
as an alternative energy
source
(in the brain as well)
Citrate
cycle
The figure is found at http://www.richmond.edu/~jbell2/19F18.JPG (Jan 2007)
animation 1
animation 2
The figure is adopted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations,
4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
simplification:
The figure is found at http://www.sp.uconn.edu/~bi107vc/images/mol/krebs_cycle.gif (December 2006)
The figure is found at http://www.holon.se/folke/kurs/Distans/Ekofys/Recirk/Eng/regcyc5.jpg (December 2006)
Amphibolic nature
of the
citrate cycle
The figure is found at
http://www.tcd.ie/Biochemistry/IUBMB-Nicholson/gif/13.html
The figure is found at http://www.elmhurst.edu/~chm/vchembook/images/590metabolism.gif (December 2006)
Products of the citrate cycle
The figure is found at http://www.hupe.hu/szerv/tanszekek/kio/im/oktat/SEJTBIO/citratkor/citr_summa_e.html
(December 2006)
„F“ → Fumarate and
FADH2
The figure is found at http://lecturer.ukdw.ac.id/dhira/Metabolism/Respiration.html (December 2006)
The figure is found at http://lecturer.ukdw.ac.id/dhira/Metabolism/Respiration.html (December 2006)
The figure is found at http://web.indstate.edu/thcme/mwking/tca-cycle.html (prosinec 2006)
The most important anaplerotic reaction:
pyruvate carboxylase
The figure is found at http://www.bmb.leeds.ac.uk/illingworth/metabol/2120lec3.htm#krebs (December 2006)
Regulation of CC
strongly exergonic
reactions
The figure is found at http://www.metabolic-database.com/html/body_glutaminolysis__zeichnung3.html (December 2006)
Regulation of the citrate cycle
= by availability of substrates and consumption of produts
regulatory
enzyme
citrate synthase
isocitrate
dehydrogenase
activation
inhibition
• ↑ NADH / NAD+
• succinyl-CoA
• ↓ ATP / ADP • ↑ NADH / NAD+
• ↑ ATP / ADP
(key enzyme)
2-oxoglutarate
dehydrogenase
• Ca2+
• ↑ NADH / NAD+
• ↑ ATP / ADP
• GTP
• succinyl-CoA
↑ATP
The figure is found at http://www.metabolic-database.com/html/body_glutaminolysis__zeichnung3.html (December 2006)
Citrate
•
is formed from oxaloacetate and activated
acetic acid (acetyl-CoA)
•
is transported to the cytoplasm if its
concentration in a mitochondrion rises
•
participates in inhibition of glycolysis
•
activates fatty acid synthesis
excess of energy is stored in glycogen and fat
Recommended animations
- SUMMARY 1.
Essential Biochemistry / Wiley & Sons
(Exercises: 10, 11, 16, 17, 19, 20)
http://www.wiley.com/college/pratt/0471393878/student/exercises/index.html
2.
Interactive Concepts in Biochemistry / Boyer
http://www.wiley.com/legacy/college/boyer/0470003790/animations/animations.htm
3.
Fundamentals of Biochemistry / Voet
http://www.wiley.com/college/fob/anim/
4.
Schematic Pathways / Hardy
http://ull.chemistry.uakron.edu/Pathways/index.html
5.
Virtual Cell Animation Collection
http://vcell.ndsu.nodak.edu/animations/home.htm