Metabolism in the Fed and Fasting States

Fuel source kJ gramsTG’s 590,000 15,000Glycogen in liver 1500 90Glycogen in muscle 6000 350Free glucose 320 20Protein 100,000 6000

Fuel Reserves in a 70 kg man

Metabolism of Carbohydrate, Lipid, & Protein

• TCA & ETC - common to all 3.

• All 3 give Acetyl CoA

• This catabolic pathway also:– Produces CO2

– Produces ATP – Produces NADH & FADH– Produces more ATP in ETC.

The principal fuels are:GlucoseLactateFatty acidsKetone bodiesAmino acids

Glycerol and ethanol can be used only to a minor degree.

Glycogen is not a fuel, it is a storage molecule. Its breakdown product, glucose, is a fuel.Circulating triacylglycerols are not fuel. Fatty acids derived from their hydrolysis are.Not all cells use all fuels at all times and not all cells can process all fuels.

Principal Fuel Metabolism of Tissues

Fuel used and/or stored and the fuel released form:

1) Brain

2) Liver

3) Adipose

4) Muscle

5) RBC

• Brain Glucose None• Ketone bodies

• Liver Glucose, Glucose from amino acids by gluconeogenesis• Glycogen for raising blood glucose• Proteins form amino acids • Lipoproteins & fatty acids.

• Adipose tissue Glucose Fatty acids, glycerol, Triglycerides• Branched-chain • fatty acids• amino acids

• Muscle Glucose, Lactate, alanine, and glutamine• Fatty acids (anaerobic gives lactate, transported as• Ketones alanine. Glutamate from catabolism of aa)• Amion acids • Glycogen is for use of muscle only• • RBC Glucose only (No mitochondria) •

(FED & Fasting States)Five Phases of Glucose Homeostasis

• Absorptive, postabsorptive, and early starvation occur sequentially over ~2 days.

• Intermediate, and prolonged starvation are over 38 subsequent days and beyond

The Fed-Fast Cycle• Stages of fed-fast cycle

Fed state lasts 3 hours after meal ingestion.Postabsorptive/early fasting state 3 to 12-18 hours after mealFasting state 18 hours to 2 days after meal when nothing else eatenStarvation/long-term fast deprivation (Weeks)

• The fed stateGlucose glycogen (Glycogenesis).Fatty acids synthesis (Lipogenesis).aa Protein (Protein synthesis).Glucose ATP (Glycolysis). ATP from glucose is used by:

nervous tissues (Brain)RBCsAdipose tissuesMuscle tissues

Fuels in Fed State

Metabolism in Fed State

• The postabsorptive/early fasting state

Glycogen glucose (Glycogenolysis). (in liver & muscle)Amino acids (primarily) 3 used for (Gluconeogenesis).GlycerolLactate

Glucogenic amino acids

1. Serine 2. Valine 3. Histidine 4. Arginine 5. Cysteine 6. Proline 7. Alanine 8. Glutamate 9. Glutamine 10.Aspartate 11.Asparagine 12.Methionine

• The fasting stateAmino acids (primarily) (Protein Breakdown)GlycerolLactate Above 3 used for (Gluconeogenesis)Fatty acids acetyl CoA Ketone formation

(Lipolysis & Ketogenesis)Ketone bodies are:

Acetoacetate Beta hydroxybutyrateAcetone.

FATTY ACIDS

FATTY ACYL CoA

CoA

β-OXIDATION

ACETYL CoA

KETONES

• The starvation state:

Fatty acids used to greater extent

Glycerol major glucose source

Ketosis after oxaloacetate depletion

Because oxaloactate comes from glucose which is deficient in starving state.

Amino Acid Metabolism

• Fed state: used for synthesis of proteins & excess is degraded (Protein synthesis & Urea cycle)

• Fasting state:Catabolism for energy produces quantities of N

(Excreted in urea), (Urea cycle)

Gluconeogensis in liver & kidneys

Five Phases of Glucose Homeostasis

• Absorptive, postabsorptive, and early starvation occur sequentially over ~2 days.

• Intermediate, and prolonged starvation are over 38 subsequent days and beyond

In general

• Brain is simply a fuel consumer• Liver and adipose tissue function as fuel

storage tissues and reservoirs• Muscle is both source and consumer leaning

heavily toward consumption• Kidney is only a significant source under

starvation

The Central Role of the Liver in Metabolism

• Glycolysis • Glycogenesis• Glycogenolysis• Gluconeogenesis• Urea formation (cycle)• Protein synthesis• Lipoprotein synthesis• Catabolism, conversion to other compounds

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