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19 Cards in this Set

  • Front
  • Back
What is Metabolism?
The sum total of chemical reactions occurring in cells.
What are the major divisions of Metabolism?
- Catabolism: energy yielding (ATP yielding) conversion of fuels to end products
- Anabolism: energy requiring (ATP requiring) bio synthetic processes
Glycolytic Pathway
- Energy generating pathway involving the conversion of glucose, or some other sugar, to pyruvate
- Occurs in cytosol
- Enzymes are soluble
- Generates 2 ATP for each glucose converted to 2 pyruvate
- Redox agents are 2 NAD+ to NADH + H+
Glycolysis Step 1
Hexokinase Reaction
- Glucose + ATP to Glucose 6-phosphate + ADP
- Irreversible
- Regulated by Hexokinase
- Once Glu 6-P is formed, it cannot exit cell, because phosphorylated compounds are generally membrane- impermeable
- Once G6P is formed, all intermediates in pathway are also phosphorylated and trapped in cell
Hexokinase
- An allosteric enzyme inhibited by its product, Glu 6-P
- Found in most cells
Glucokinase
- Specialized hexokinase found in the liver
- Suited to liver's role as chief feeder of other tissues in the body
- Kinetic properties are suited to the fact that blood arriving in the liver from the intestines will have widely varying glucose concentrations, depending upon dietary state
- See slide for Kinetic Properties of HK and GK
Glycolysis Step 2
Phosphoglucoisomerase (PGI) Reaction
- Glu 6-P = Fructose 6-P
- Regulated by PGI
- Reversible
- A Moonlighting protein: catalyzes inside of cell, nerve growth factor outside of cell
Glycolysis Step 3
Phosphofructokinase 1 (PFK-1) Rxn
- Fru 6-P + ATP to Fru 1,6 Bisphosphate + ADP
- Reg by PFK- 1
- Irreversible
- Most IMPORTANT (step) control point in glycolytic pathway
- ATP inhibits
- AMP and Fru 2,6 BP activate
- Enzyme has 2 binding sites for ATP, one a substrate-binding site and the other allosteric.
Allosteric Inhibition and Activation (ATP & F 2,6 BP)
ATP:
(-) : Allosteric Inhibitor
(+): Allosteric Activator
* In Low concentrations, ATP is a substrate. In High concentrations, ATP is an allosteric inhibitor
F 2,6 BP:
(-): Allosteric inhibitor
(+): Allosteric activator
Glycolysis Step 4
Fructose Bisphosphate Aldolase
- Fru 1,6 BisP = Glyceraldehyde 3-P + Dihydroxyacetone P
- Top half of hexose becomes DHAP and the bottom becomes Glycer 3P (see lecture notes)
- Reaction occurs in cells even with deltaGknot'= +23.9kj/mol
Glycolysis Step 5
Triose Phosphate Isomerase
- This step interconverts th two triose phosphates:
Glycer3P = DHAP
- Since only Glycer3P has a further fate in glycolytic pathway, it is as if 2 Glycer3P are produced per molecule of glucose
Glycolysis Step 6
Glyceraldehyde Phosphate Dehydrogenase
- Glycer3P + NAD+ + Pi = 1,3 BPG + NADH + H+
- 2 NAD+ is reduced per 1 glucose
- The phosphate at position 1 is a phosphoanhydride and has a free energy of hydrolysis
- The phosphate at position 3 is a phosphoester and has a low free energy of hydrolysis
- The enzyme is inactivated by iodoacetate, implying that a Cys-SH is necessary for activity.
Glycolysis Step 10
Pyruvate Kinase
- PEP + ADP to Pyruvate + ATP
- Irreversible and regulatory
- Allosteric activator: F1,6BP, an example of feed-forward activation
- Allosteric inhibitor: ATP
- A net of 2 ATP produced in this step from glucose
Anaerobic Fate of Pyruvate
Lactate Dehydrogenase
- Pyruvate + NADH + H+ = Lactate + NAD+
- When Oxygen is in short supply in tissues like voluntary skelatal muscle under conditions of rigorous exercise, lactate, rather than pyruvate, is the end product of glycolysis
- The function of this terminal step is to regenerate NAD+ for the Glycer3P dehydrogenase reaction (or re-oxidize NADH for step 6)
- See slide for picture
Glycolysis Step 7
Phosphoglycerate Kinase
- 1,3 BPG + ADP = 3-PGA + ATP
- The high energy phosphate at position 1, the phosphoanhydride, can be transferred to ADP to generate an ATP
Glycolysis Step 8
Phophoglycerate Mutase
- 3-PGA = 2-PGA
Glycolysis Step 9
Enolase
- 2-PGA = PEP
- PEP is phosphoenolpyruvate. It is a high energy phosphate compound
Glycolysis Net Reaction
- Total of 4 ATP is generated
- 2 used to phosphorylate glucose and F6P
- Net ATP yield is 2
- Glucose + 2 ADP + 2Pi = 2 Lactate + 2 ATP + 2 H2O
Labeling Relationships
- Carboxyl group of lactate comes from C3 and C4 of glucose
- Middle carbon atom of lactate come from C2 and C5
- Methyl carbon atom comes from C1 and C6
- See lecture for illustration