DENTAL BIOCHEMISTRY 2015 LECTURE 13 METABOLIC COMPARTMENTATION Michael Lea.
-
Upload
johnathan-horn -
Category
Documents
-
view
216 -
download
2
Transcript of DENTAL BIOCHEMISTRY 2015 LECTURE 13 METABOLIC COMPARTMENTATION Michael Lea.
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 recognitionmetabolite transport
Cytosol:glycolysispentose phosphate pathwaylipid synthesis
Mitochondrion:fatty acid oxidationTCA cycleelectron transportoxidative phosphorylation
Lysosome:hydrolases
Peroxisome:peroxidationoxidation of very long chain fatty acids
Endoplasmic Reticulum:protein synthesisxenobiotic metabolism
Golgi:glycosylation, sulfation
Nucleus:DNA synthesisRNA 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
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