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Metabolism
is the set of chemical reactions that happen in living organisms to maintain life
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NORMAL METABOLISM IS A HIGHLY CONTROLLED AND REGULATED and is a
BALANCE BETWEEN ANABOLISM AND CATABOLISM
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CATABOLIC PROCESSES RELEASE CHEMICAL ENERGY STORED IN COMPLEX MOLECULES such as
ENERGY SAVED AS ATP, NADH, NADPH, FADH2 OR USED AS NEEDED IN VARIOUS PROCESSES
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ANABOLIC PROCESSES BUILD COMPLEX MOLECULES FROM SIMPLER MOLECULES and REQUIRE ENERGY USUALLY FROM
ATP, NADH, NADPH and FADH2
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METABOLIC FUELS (STORAGE MOLECULES)
PROTEINS, POLYSACCHARIDES, LIPIDS
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Catabolism
is the set of pathways that break down molecules into smaller units and release energy
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Glycolysis will happen in both
Aerobic and anaerobc environments
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Under anaerobic conditions, the end product of glycolysis is
Two molecules of lactic acid. (often referred to as lactic acid fermentation)
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Under aerobic conditions, the end product is
Two molecules of ATP per molecule of glucose as well as two NADH
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Glycolysis takes place in
the cytosol
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Some organisms (yeast) under anaerobic conditions convert pyruvate
to ethanol; alcoholic fermentation
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Gluconeogenesis
Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors such as pyruvic and lactic acid.
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Glucose characteristics
Very soluble source of quick and ready energy.
It is a relatively stable and easily transported.
In mammals, the brain uses only glucose under non-starvation conditions.
Under starvation conditions ketone bodies become a source of energy for the brain
Glucose is the only source of energy in red blood cells.
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A hexokinase is
The first step of glycolysis (not reversible) has a low Km and low Vmax
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Liver also contains a specialized form of hexokinase known as
glucokinase
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Hexokinase is inhinited by
Glucose-6-Phosphate (Its product)
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Glucokinase characteristics
much higher Km for glucose, is not inhibited by glucose 6-phosphate, is absent in muscle and is deficient in patients with diabetes
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At normal blood glucose concentrations hexokinase is
fully saturated, glucokinase is not
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Glucokinase is present at high concentration in
The liver and is induced in response to D-glucose
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Glucokinase assures that at high concentrations (like that following a carb rich meal)
Glucose is not wasted. Instead it is converted to glucose 6-phosphate for subsequent synthesis of glycogen
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Hexokinase can also phosphorylate
fructose, mannose, and glucosamine, whereas glucokinase cannot.
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First reaction does not commit glucose to glycolysis, since
Glucose-6-phosphate represents a branch point in carbohydrate metabolism. It also enters pentose phosphate pathway and glycogenesis.
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PFK-1 (Phosphofructokinase-1) is an important allosteric enzyme which
Regulates the rate of glucose catabolism and plays a role in integrating metabolism. (Committed step)
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The PFK reaction is the first unique and irreversible step in
The glycolytic pathway
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PFK1 is inhibited by
High ATP
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PFK is triggered by
High AMP and even more so by Fructose 2,6 bisphosphate
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Phosphorylation is
the addition of a phosphate (PO4) group to a protein or other organic molecule
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The Conversion of Glucose to Pyruvate
- Glucose + 2 Pi + 2 ADP + 2 NAD+ →
- 2 pyruvate + 2 ATP + 2 NADH +2 H
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The Energy released from the anaerobic conversion of glucose to pyruvate is
-47kcal
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In what conditions can much more chemical bond energy be extracted from pyruvate.
Under aerobic conditions
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Under anaerobic conditions pyruvate is converted to
lactate. Exercising muscle is an example.
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Cori cycle:
the liver furnishes glucose to contracting skeletal muscle, which derives ATP from the glycolytic conversion of glucose into lactate. Contracting skeletal muscle supplies lactate to the liver, which use it to synthesize glucose. 
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The NAD+ that is consumed in the glyceraldehyde 3-phosphate reaction is
produced in the lactate DH reaction. Thus, redox balance is maintained.
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The NADH that is produced in the glyceraldehyde 3-phosphate reaction is
consumed in the lactate DH reaction. Thus, redox balance is maintained.
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The three regulatory steps in glycolysis are
- 1. Hexokinase
- 2. Phophofructokinase
- 3. Pyruvate Kinase
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Floride can inhibit whatt step in glycolysis
Enolase
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The first ATP producing step is
Phosphoglycerate Kinase (2ATP)
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The two steps that require ATP are
Hexokinase, Phosphofructokinase
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What step can Arsenate effect
Glyceraldehyde 3-Phosphate dehydrogenase (the first Redox)
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What is found in high amounts in the red blood cells but not in in others
2,3 BPG
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In normal cells the redox state is the ratio
- NAD+/NADH + H+ =8/1
- In excess of alcohol 1/1
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High NADH causes
inhibition of gluconeogenesis (prevent oxidation of lactate to pyruvate)= lactate accumulation
Inhibits fatty acid oxidation, stimulating fatty acid synthesis in the liver = fatty liver
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Fructose 2,6-Bisphosphate (which regulates PFK1) is synthesized by
PFK2
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What increases F2,6-BP
A high Insulin/Glucagon ratio after a high carb meal
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What regulates the PFK1 level in the liver and adipose tissue
F2,6-BP
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Glucagon is only active where
In the liver
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What are the steps of the signaling cascade for deactivation of glycolysis in the liver
Activation of PKA---Phosphorilation of PFK-2----breakdown of F2,6-BP---Decrease in PFK1
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Epinephrine in the Liver limits glycolysis by
Elevates cAMP, Increasing the breakdown of PFK-2 thus making less F2,6-BP to activate glycolysis
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Epinephrine in the heart has what effect on glycolysis
- Increases cAMP, increasing PFK-2 Kinase.
- This activates F2,6-BP increasing glycolysis in the heart (Fight or Flight Response)
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Lactate fermentation and alcohol fermentation have what in common
The use up the NADH's produced by glycolysis
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The reaction that requires a continuous supply of NAD+ is
Glyceraldehyde 3-phosphate Dehydrogenase (G3PD)
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Glucagon activates fructose-2,6-bisphophatase to decrease fructose2,6-bisphosphate concentration when
Blood glucose levels are low
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A high carb meal translates to
High insulin and low glucagon
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Decreased lactate production in the eurythrocytes indicates
A defect in glycolysis (95% of the people showing a defect of glycolytic enzymes are attributed to pyruvate kinase)
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What is the reaction intermediate of ethanol breakdown that causes a hangover
Acetylaldehyde
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What is hemolytic anemia, and how does glycolysis relate to it
The abnormal breakdown of RBCs.
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When pyruvate kinase isn't functioning ATP is low. Without ATP the RBC's can't use their pumps causing an inproper ion balance deforming the cell
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