Transcript METABOLIC COMPARTMENTATION

DENTAL BIOCHEMISTRY 2015
LECTURE 13
METABOLIC COMPARTMENTATION
Michael Lea
LECTURE OUTLINE
• Subcellular organelles in eukaryotic
cells
• Location of enzymes and metabolic
pathways
• Transport of metabolites across
membranes
• Glycerol phosphate and malate electron
transport shuttles
• Aerobic and anaerobic yields of ATP
from glucose metabolism
Suggested Reading
• Lippincott’s Biochemistry, 6th edition,
pages 79-80
EUKARYOTIC SUBCELLULAR ORGANIZATION
Plasma membrane:
hormone and cytokine recognition
metabolite transport
Cytosol:
glycolysis
pentose phosphate pathway
lipid synthesis
Mitochondrion:
fatty acid oxidation
TCA cycle
electron transport
oxidative phosphorylation
Lysosome:
hydrolases
Peroxisome:
peroxidation
oxidation of very long chain fatty acids
Endoplasmic Reticulum:
protein synthesis
xenobiotic metabolism
Golgi:
glycosylation, sulfation
Nucleus:
DNA synthesis
RNA synthesis
MOVEMENT OF METABOLITES
ACROSS CELL MEMBRANES
• Simple diffusion occurs with some small
molecules
• Facilitated diffusion accelerates
movement but does not operate against
a concentration gradient
• Active transport requires ATP but can
concentrate a molecule, e.g. some
amino acid transport and the Na+/K+
ATPase
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ELECTRON SHUTTLES BETWEEN THE CYTOSOL
AND THE MITOCHONDRIA
The inner mitochondrial membrane is impermeable to
NADH
Electrons from NADH in the cytosol are transferred by
electron shuttles.
In the glycerol phosphate shuttle, NADH in the cytosol is
used to reduce dihydoxyacetone phosphate in the
reaction catalyzed by cytosolic glycerol 3-phosphate
dehydrogenase. A glycerol phosphate oxidase in the inner
mitochondrial membrane catalyzes the transfer of
electrons from glycerol 3-phosphate to FAD. Reduced
FAD is oxidized by Complex II in the mitochondrial
electron transport chain.
The malate-aspartate shuttle is an alternative mechanism
for the transfer of electrons into mitochondria.
VARIABLES AFFECTING THE YIELD OF ATP FROM THE
OXIDATION OF A MOLECULE OF GLUCOSE
• Aerobic or anaerobic conditions
• Electron shuttle ( glycerol phosphate shuttle or
malate aspartate shuttle)
• Reduced coenzyme (NADH, 2.5 - 3 ATP or FADH2,
1.5 - 2 ATP)
• The complete oxidation of glucose to carbon dioxide
directly yields 2 ATP, 2 GTP, 10 NADH and 2 FADH.
Depending on the assumptions used with respect to
electron shuttle and ATP yield this could be the
equivalent of 30 to 38 ATP molecules per molecule of
glucose oxidized to carbon dioxide. Whatever the
number, it is much greater than the net 2 molecules
of ATP obtained from the anaerobic glycolysis of
glucose to two molecules of lactic acid.
LECTURE OBJECTIVES
• After studying this lecture material you should be able
to
• Describe the subcellular localization of metabolic
pathways in eukaryotic cells
• Distinguish the different mechanisms by which
metabolites cross cellular membranes
• Understand the requirement for electron transport
shuttles across the inner mitochondrial membrane
and describe two mechanisms by which the transport
is achieved
• Appreciate the large difference in yields of ATP from
glucose metabolism under aerobic and anaerobic
conditions