Transcript Integration of Metabolism

Integration of Metabolism
Cellular Locations for Metabolism
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Citric Acid Cycle, Oxidative
Phosphorelation, Fatty Acid Oxidation Mitochondria
Glycolysis - Cytosol
Fatty Acid Synthesis – Cytosol
Nucleic Acid synthesis - Nucleus
Protein Synthesis – Ribosomes & RER
Integration of Fuel Metabolism
Purine
Ribose-5-P
Glycogen
PRPP
G-6-P
monophosphate
Pyrimidine
monophosphate
Glycine
Serine
Uric acids
Malonyl CoA
G-3-P
Fatty acids
b-Oxidation
PEP
Acetoacetyl CoA
Cholesterol
Acetyl CoA
Other
amino
acids
Pyruvate
Oxaloacetate
Alanine
Aspartate
Urea
Urea
Cycle
Other
amino
acids
Triacylglycerols
TCA
Cycle a-ketoglutarate
Other
amino
Glutamate
acids
Glutamine
Glycolysis
PFK is the most important control site in glycolysis:
Cytosol
In liver, when glucose is low, glucagon activates
phosphatase to convert F-2, 6-BP to F-6-P. PFK is
Inhibited, which slows down glycolysis.
In muscle, when glucose is low, epinephrine activates
a kinase to convert F-6-P to F-2,6-BP. PFK is
Activated, which accelerates glycolysis.
Glucose-CO2-Lipids
Pyruvate d.h. complex is a
key irreversible step in
animals:
No conversion of lipids
to carbohydrates
Citric Acid Cycle
Pyruvate d.h.complex
Citrate synthase
Isocitrate d.h.
mitochondria
a-ketoglutarate d.h.
Pentose Phosphate Pathway
G-6-P d.h.
Cytosol
Gluconeogenesis
(inside ER)
(mit.)
Most in cytosol: Liver and Kidney
F-1,6-bisphosphatase
is the key control site
Integration of Fuel Metabolism
Purine
Ribose-5-P
Glycogen
PRPP
G-6-P
monophosphate
Pyrimidine
monophosphate
Glycine
Serine
Uric acids
Malonyl CoA
G-3-P
Fatty acids
b-Oxidation
PEP
Acetoacetyl CoA
Cholesterol
Acetyl CoA
Other
amino
acids
Pyruvate
Oxaloacetate
Alanine
Aspartate
Urea
Urea
Cycle
Other
amino
acids
Triacylglycerols
TCA
Cycle a-ketoglutarate
Other
amino
Glutamate
acids
Glutamine
Key Junctions: G-6-P,
Pyruvate, and Acetyl CoA
Compartmentalization of the Major Pathway
of Metabolism
Glycolysis
Pentose phosphate pathway
Communications between
different compartments
are achieved by a number of
carriers to carry metabolic
intermediates across
membranes.
Fatty acids synthesis
TCA cycle, Oxidative phosphorylation
b-oxidation of Fatty acids
Ketone body formation
Gluconeogenesis
Urea synthesis
a-Ketoglutarate
Oxaloacetate
Glutamate
Aspartate
Glutamine Proline Arginine
Asparagine Methionine Threonine Lysine
Pyruvate
Isoleucine
Phosphoenolpyruvate
Alanine Valine
Leucine
3-Phosphoglycerate
Tyrosine
Serine
Glycine
Phenylalanine Tyrosine Tryptophan
Cysteine
Ribose 5-phosphate
Histidine
Catabolism:
The
Breakdown of
Macronutrients for
Energy
Stages 1-4
Lipolysis
Stage 2: Beta
Oxidation
Lipogenesis
Gluconeogenesis
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Noncarbohydrate molecules transformed into
glucose by various anabolic pathways
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Amino acids, lactate, glycerol
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Occurs primarily in liver & kidneys
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Provides glucose to cells during starvation
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Stimulated by glucagon & cortisol
Gluconeogenesis
Gluconeogenesis from Amino
Acids
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Glucogenic amino acids
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All except leucine & lysine
Removal of amino group via
transamination & deamination along
with conversion of carbon skeleton to
oxaloacetate necessary
Requires coenzymes (B vitamins)
Ketogenesis
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Ketones
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Organic compounds used as energy source
during starvation, fasting, low-carb diets,
or uncontrolled diabetes
Ketogenesis
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Metabolic pathways used to produce
ketones
Ketones
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β-oxidation leads to substantial amounts of
acetyl CoA production
Ketone body formation is an “overflow”
pathway for acetyl CoA use
If OAA is not present, then acetyl CoA does
not go through TCA cycle and will be
converted to ketones
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Low rates of glycolysis lead to reduced OAA
production
Ketogenesis
Ketone body formation
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Ketone bodies
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Acetoacetate
β-hydroxybutyrate
Acetone
Acetyl CoA + acetyl CoA = acetoacetyl CoA
Acetoacetyl CoA – CoA = acetoacetate
Acetoacetate can be converted to acetone and
hydroxybutyrate
β-
Why is ketogenesis important?
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Muscles, brain & kidneys have enzymes
that allow them to use ketones for ATP
production
Serve as a major source of energy
during times of glucose insufficiency
Spare use of amino acids
What happens when ketone production
exceeds ketone use?
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Ketosis
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High levels of ketones in blood
When?
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Early lactation in dairy cows
Late pregnancy in sheep with multiple pregnancies
Diabetics
Ketoacidosis
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Severe ketosis
Lowered blood pH, nausea, coma, death
Ketosis
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Cure is infusion of glucose
An Introduction to Cellular Metabolism
Metabolic Turnover and Cellular ATP
Production
Nutrient Use in Cellular Metabolism
Lipid Synthesis
Lipid Transport and Utilization
Lipid Transport and Utilization
A Summary of the Pathways of Catabolism and
Anabolism
The Absorptive State
The Postabsorptive State