Series of linked reactions that convert a specific reactant into a specific product
Intermediary metabolism
Entire set of cellular metabolic reactions
ATP
Adenosine triphosphate
ATP
Energy is derived from fuels or light and converted into ATP
Contains 2 phosphoanhydride linkages
Kinetically stable, thermodynamically unstable
Kinetically stable
ATP does not spontaneously hydrolyze or break down quickly
Thermodynamically unstable
ATP has a high potential energy that can be released through hydrolysis
Energy released via ATP hydrolysis is -30.5 kJ/mol
ATP formation
1. Chemotrophs: ADP and Pi form ATP when fuel molecules are oxidized
2. Autotrophs: ATP is formed when light is trapped
Phosphoryl-transfer potential
Tracks the ability of different organic molecules to transfer a phosphoryl group to water
High in ATP
Charge repulsions
Resonance stabilization
Increase in entropy
Stabilization of ADP and Pi by hydration
Catabolic pathways
Synthesize ATP or ion gradients
Combust carbon fuels
Break down molecules
Anabolic pathways
Use ATP and reducing power to synthesize large biomolecules
Create molecules
Amphibolic pathways
When a pathway is both catabolic or anabolic
Example: TCA Cycle
For a thermodynamically unfavorable reaction to occur in a metabolic pathway, it can be coupled with a more favorable reaction
The oxidation of carbon fuels is an important source of cellular energy
Oxidation state of a carbon atom
The more reduced a carbon atom is, the more free energy is released upon oxidation
Activated carriers
A small number of recurring activated carriers transfer activated groups in many metabolic pathways
Transfer is highly exergonic
Very kinetically stable and can be regulated by enzymes
Often derived from vitamins
Energy charge
Depends on the relative amounts of ATP, ADP, AMP
Fluctuates over time
Can range from 0 to 1
High energy charge inhibits catabolic (ATP-generating) pathways and stimulates anabolic (ATP utilizing) pathways
Glycolysis
1. Investment phase: Steps 1-5
2. Yield phase: Steps 6-10
Glycolysis steps
Substrates
Enzymes
Products
Fermentation
ATP generating pathways in which electrons are removed from one organic compound and passed to another organic compound
Allows NAD+ to be regenerated (oxidized) and reused from NADH
Alcoholic (ethanol) fermentation
1. Glucose forms 2 molecules of ethanol
2. Enzyme: alcohol dehydrogenase
Lactic acid fermentation
1. NADH is oxidized by converting pyruvate to lactate
2. Conversion of glucose into 2 molecules of lactate
3. Enzyme: lactate dehydrogenase
Glucose + 2 Pi + 2 ADP → 2 lactate + 2 ATP + 2H20
Control sites in glycolytic pathway
Step 1: Hexokinase
Step 3: PFK (phosphofructokinase)
Step 10: Pyruvate kinase
Glycolysis regulation in muscle
Primarily regulated by energy charge of the cell
Hexokinase, PFK, and pyruvate kinase are allosterically regulated
Glycolysis regulation in liver
Hexokinase regulated by glucose 6-phosphate
PFK regulated by citrate and fructose 2,6-bisphosphate
Pyruvate kinase regulated by allosteric and covalent modification
Glycolysis in muscle is primarily regulated by energy charge
Liver's role in glycolysis regulation
Liver is a primary site for biosynthesis
Regulated by need to maintain blood glucose levels
Hexokinase vs glucokinase
PFK regulated by citrate and fructose 2,6-bisphosphate
Pyruvate kinase regulated by phosphorylation
Conversion of fructose and galactose into glycolytic intermediates
1. Galactose enters as glucose 6-phosphate
2. Fructose: Most tissues - directly phosphorylated by ketohexokinase
3. Liver - metabolized by the fructose 1-phosphate pathway
Gluconeogenesis
The synthesis of glucose from pyruvate
Major site: Liver
Also occurs in the kidney
Gluconeogenesis is especially important during fasting or starvation
Noncarbohydrate precursors for gluconeogenesis
Pyruvate
Carbon skeletons of some amino acids
Glycerol (derived from the hydrolysis of triacylglycerols)
Gluconeogenesis vs glycolysis
Not a simple reversal of glycolysis
3 irreversible steps of glycolysis must be bypassed
Unique reactions: Conversion of pyruvate to phosphoenolpyruvate, Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate, Conversion of glucose 6-phosphate to glucose
Liver's role in gluconeogenesis
The final step of gluconeogenesis only occurs in the liver
Generation of free glucose is an important control point
The liver is able to perform gluconeogenesis at a significant rate
6 high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate in gluconeogenesis
Reciprocal regulation of glycolysis and gluconeogenesis
Within a cell, one pathway is relatively inactive while the other is highly active
Glycolysis will predominate when glucose is abundant and gluconeogenesis will be highly active when glucose is scarce
Energy charge determines which pathway will be more active
Role of fructose 2,6-bisphosphate in glycolysis/gluconeogenesis regulation