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3/15/2011

Integration of Metabolism

Metabolic Pathways are Interconnected

3/15/2011

Metabolic Pathways are Interconnected


1. ATP is the universal currency of energy 2. ATP is generated by oxidation of glucose, fatty acids, and amino acids ; common intermediate -> acetyl CoA ; electron carrier -> NADH and FADH2 3. NADPH is major electron donor in reductive biosynthesis 4. Biomolecules are constructed from a small set of building blocks 5. Synthesis and degradation pathways almost always separated -> Compartmentation !!!

Metabolic Profiles of Different Organs

3/15/2011

Metabolic Profile of the Brain

Glucose is fuel for human brain consumes 120g/day 60-70 % of utilization of glucose in starvation ketone bodies can replace glucose

Metabolic Profile of Muscles

3/15/2011

Metabolic Profile of Adipose Tissues

Triacylglycerols are stored in tissue enormous reservoir of metabolic fuel needs glucose to synthesize TAG glucose level determines if fatty acids are released into blood

Metabolic Profile of Kidneys


production of urine secretion of waste products blood plasma is filtered 60x per day water and glucose reabsorbed during starvation important site gluconeogenesis (1/2 of blood glucose) of

3/15/2011

Metabolic Profile of the Liver

Essential for providing fuel to brain, muscle, other organs most compounds absorbed by diet pass through liver regulates metabolites in blood

Food Intake, Starvation, and Obesity


Normal Starved-Fed Cycle Postabsorptive State after a meal Early Fasting State during the night Refed State after breakfast
major goal is to maintain blood-glucose levels

3/15/2011

Food Intake, Starvation, and Obesity


Postabsorptive State
Glucose + Amino Acids transport from intestine to blood Dietary lipids lymphatic system to blood Glucose stimulates secretion of insulin

Food Intake, Starvation, and Obesity


Postabsorptive State
Insulin signals fed state stimulates storage of fuels and synthesis of proteins glucose enters muscle + adipose tissue synthesis of TAGs stimulates glycogen synthesis in liver accelerates glycolysis in liver increases synthesis of fatty acids suppresses gluconeogenesis by the liver

3/15/2011

Food Intake, Starvation, and Obesity


Early Fasting State
bloodglucose levels drop after several hours after the meal decrease in insulin secretion

low bloodglucose levels stimulate secretion of glucagon by cells of pancreas

Food Intake, Starvation, and Obesity


Early Fasting State
Glucagon signals starved state mobilizes glycogen stores (break down) inhibits glycogen synthesis main target organ is liver inhibits fatty acid synthesis stimulates gluconeogenesis in liver large amount of glucose from the liver is released to blood stream muscle + liver use fatty acids as fuel when blood glucose levels drops

3/15/2011

Food Intake, Starvation, and Obesity


Refed State
fat is processed in same way as normal fed state liver does not absorb glucose from blood (diet) liver still synthesizes glucose to refill livers glycogen stores when liver has refilled glycogen stores + blood glucose levels still rises liver synthesizes FAs from excess glucose

Food Intake, Starvation, and Obesity


Prolonged Starvation
wellfed 70 kg human fuel reserves 161000 kcal energy needed for a 24 h period 1600 to 6000 kcal sufficient reserves for starvation up to 13 months however glucose reserves are exhausted in 1 day bloodglucose level must be above 40 mg/100 mL

3/15/2011

Food Intake, Starvation, and Obesity


Prolonged Starvation
1st priority provide sufficient glucose to brain and other tissues that are dependent on it

2nd priority preserve protein; shift from utilization of glucose to utilization of FAs and ketone bodies

mobilization of TAGs in adipose tissues + gluconeogenesis by liver muscle shift from glucose to FAs as fuel

Food Intake, Starvation, and Obesity


Prolonged Starvation
after 3 days of starvation liver forms large amounts of ketone bodies (shortage of oxaloacetate) released into blood brain and heart start to use ketone bodies as fuel after several weeks of starvation ketone bodies major fuel of brain after depletion of TAG stores protein degradation accelerates death due to loss of heart, liver, and kidney function

3/15/2011

Key Junctions in Metabolism

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