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Contents • Aims and objectives • Glycolysis • TCA cycle • Insulin and glucagon
Metabolism
• Fed state
Created by Sophia Oxenburgh ©
• Fasting state • Summary
Aims and Objectives • For each metabolic pathway have an awareness of: – Substrate and product – Important enzymes – Main regulatory mechanisms
• An understanding of how pathways fit together • An understanding of the differences between fed and fasting states
Quick Reminder
Glycolysis • First step of cellular
Brain
Muscle
Glucose
Glucose
Ketone bodies
Ketone Bodies Fatty acids
respiration • There are LOTS of steps • Regulated by – hexokinase – PFK-1 – pyruvate kinase
• Aerobic v anaerobic
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Glucose
Tricarboxylic Acid Cycle
Glucose 6-P
Hexokinase/Glucokinase Pyruvate
Fructose 6-P
Fructose 1,6-bis-P
Phosphofructoskinase-1 Glyceraldehyde 3-P
1,3-bis-Phosphoglycerate
Pyruvate kinase
Dihydroxyacetone-P
Amino Acids Acetyl CoA
Pyruvate dehydrogenas e
Citrate
Glucose
Oxaloacetate
Isocitrate
CO2
Amino Acids αKetoglutarate
Malate
3-Phosphoglycerate
Amino Acids
CO2
2-Phosphoglycerate
Pyruvate dehydrogenase Phosphoenolpyruvate
Lactate
Pyruvate
Fed State
Amino Acids
Fumarate
Succinyl CoA Succinate
Amino Acids
Insulin and Glucagon • α vs β cells • GLUT-4 transporter • Control mechanisms
Glycogenesis Glycogen synthase
What happens to the excess glucose? Glucokinase/hexokinase
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Exogenous Pathway Dietary Fat and Cholesterol Free Cholesterol
Cholesterol and Bile Acids
Intestine
CM
Chylomicron
FFA
LDLR LRP
RLP Remnant Capillary
Adipose LPL
Nascent HDL
Free Fatty Acids
Endogenous Pathway Free Cholesterol
The big picture
LDLR
HTGL
Liver
LDL
LDLR LRP
B100
HTGL
Liver Free Cholesterol
ApoB
Free Cholesterol
SR-B1
LDLR
LDL
LDLR LRP
ApoB
Triglyceride
A1
Triglyceride
VLDL
IDL
CM
Glucose
LPL
RLP E
Nascent HDL
HDL
Free Cholesterol
B48
VLDL
Capillary FFA
Muscle
IDL
E
ABCA1
B100
Capillary
Peripheral Tissues Intestine
Free Fatty Acids (FFA)
LPL
Free Fatty Acids (FFA)
What happens to the excess?
Peripheral Tissues
Nascent HDL
Esterification Fatty acyl CoA synthetases
Fatty acid synthase
Glucose
Fatty acid
Fatty acyl CoA
Acetyl CoA carboxylase Glycerol phosphate dehydrogenase Pyruvate
Fatty Acid Glycolysis
DHAP
Glycerol phosphate
Acyltransferase Triacylglycerol
Malonyl CoA
Glycerol kinase
Acetyl CoA
Phosphatase Free glycerol
Oxaloacetate
Citrate
Pi
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Amino Acids • Essential vs non-essential amino acids • Nitrogen NOT stored in the body • Very complex mechanism
Fasted State
Glycogenolysis
Glycogen phosphorylase
Phosphoglucomutase
Glucose 6-phosphatase
Glucose
Lipolysis
Glucose 6-P
Hexkinase
Glucose 6-phosphatase Fructose 6-P
Hormone sensitive lipase
Glycerol
Fructose 1,6-bis-P
PFK-1
Β-oxidation
Fructose 1,6-bisphosphatase Glyceraldehyde 3-P
Triacylglycerol
1,3-bis-Phosphoglycerate
Pyruvate kinase
Pyruvate carboxylase PEP carboxykinase
3-Phosphoglycerate
2-Phosphoglycerate
Fatty acid
Fatty acyl CoA
Acetyl CoA
Fatty acid acyl CoA synthetase
Phosphoenolpyruvate
Lactate
Pyruvate
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Ketone Bodies 3-hydroxybutyrate dehydrogenase
HMG CoA synthase
3Hydroxybutyrate
Fatty acid
Acetoacetyl CoA
HMG CoA
Acetoacetate
Acetone
Acetyl CoA
HMG CoA lyase
Homework • Fructose metabolism • Oxidative phosphorylation • Urea cycle • Phenylketonuria
Summary • For each metabolic pathway have an awareness of: – Substrate and product – Important enzymes
– Main regulatory mechanisms
Any Questions?
• An understanding of how pathways fit together • An understanding of the differences between fed and fasting states
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