Organic Metabolism Topics

1. Absorptive and Post Absorptive States

2. More on the different forms of fat found in the blood

3. Neuroendocrine regulation of metabolism

4. Diabetes Mellitus (Type 1 and Type 2)

Metabolism: Absorptive State Reactions

Absorptive vs. Postabsorptive States

• Absorptive State:

  • Period during which ingested nutrients are entering the blood from the gastrointestinal (GI) tract.

  • Energy is primarily supplied by glucose from ingested nutrients.

  • Remaining nutrients are added to the body’s energy stores.

• Postabsorptive State:

  • Period during which the GI tract is empty of nutrients.

  • Energy is primarily supplied by the body’s fat stores, particularly fatty acids.

Fate of Absorbed Nutrients

Fate of Monosaccharides (Carbohydrates)

• Main dietary sugars include glucose, fructose, and galactose, which can enter the glycolytic pathway or be stored as glycogen.

1. Monosaccharides travel from the GI tract to the liver:

   • Liver Actions:

     • Catabolized for energy.

     • Stored as glycogen.

     • Converted to fatty acids and alpha-glycerol phosphate.

2. Monosaccharides that are not taken up by the liver enter the systemic circulation:

   • Primarily taken up by skeletal muscle cells (which constitute 40-50% of body mass).

   • In muscle, glucose is either catabolized for energy or stored as glycogen.

   • Non-muscle cells will catabolize glucose for energy.

   • In adipocytes, glucose is converted to alpha-glycerol phosphate or fatty acids, then synthesized into triglycerides.

Fate of Amino Acids

Transport and Utilization:

1. Amino acids enter liver cells:

   • Synthesize proteins or convert to alpha-ketoacids.

   • Alpha-ketoacids can enter the Krebs cycle or be converted to fatty acids.

2. In non-liver cells:

   • Synthesized into proteins, particularly in skeletal muscle, which holds the majority of amino acid uptake.

3. Excess amino acids:

   • Taken up by the liver, converted to alpha-ketoacids, subsequently converted to fatty acids, and incorporated into triglycerides and very low density lipoproteins (VLDL).

   • Triglycerides released from the liver are stored in adipocytes.

Fate of Fat (Triglycerides)

• Terminology:

  • Triglyceride (TG) = Triacylglycerol (TAG)

  • Alpha-glycerol phosphate = Glycerol-3-phosphate

• Most monoglycerides return to the liver for metabolism.

• Triglycerides in the blood are digested by lipoprotein lipase to release free fatty acids and monoglycerides.

• Upon entering circulation, small amounts of monoglycerides will enter adipocytes for triglyceride formation.

Lipoprotein Infrastructure

Lipoprotein Lipase and Actions

• Glycerol produced in adipocytes from glucose metabolites is pivotal during absorptive states.

Steps During Absorptive State:

• Steps 1-5 involving lipid metabolism, particularly triglycerides, occur in the absorptive state, while steps 6 and 7 happen during postabsorptive states.

• Hormone-sensitive lipase (HSL) is responsible for the breakdown and release of triglycerides stored in adipocytes.

Transport of Triglycerides

• Triglycerides are transported in circulation, packaged in chylomicrons (from the GI tract) or VLDLs (synthesized in the liver).

• Chylomicrons and VLDLs express Apo (apolipoproteins) on their surface, key for metabolic interactions.

Functional Role of Apolipoproteins:

• Apolipoprotein Types:

  • VLDLs and chylomicrons express ApoB.

  • While circulating, they gain ApoC-II, which is necessary for functioning with lipoprotein lipase.

  • Capillary endothelial cells have lipoprotein lipase, which releases fatty acids from lipoproteins to be used primarily by adipocytes (to convert into triglycerides for storage) and myocytes (for beta-oxidation to produce ATP).

Exam Type Question 1

• Triglycerides absorbed from the GI tract can be:

  • Taken up by the liver and repackaged into VLDLs for delivery to adipose tissue.

  • Used for glycogen synthesis in skeletal muscle.

  • Broken down by lipoprotein lipase into monoglycerides and fatty acids, absorbed into adipocytes.

  • Released fatty acids in brain capillaries may be taken up by neurons for ATP generation.

  • Broken down by hormone-sensitive lipase in the capillaries, and fatty acids are absorbed into adipocytes.

Quiz 1

• Assessing understanding of glucose and amino acid uptake in the absorptive phase, as well as circulating fats.

The Post-Absorptive State

Overview

• Metabolic state where net anabolism of glycogen, fat, and protein ceases, and net catabolism begins.

• Central nervous system (CNS) relies solely on glucose for energy, necessitating maintenance of plasma glucose levels.

• Blood glucose is sustained via:

  • Glycogenolysis (breakdown of glycogen).

  • Gluconeogenesis (production of glucose from non-carbohydrate sources).

  • Glucose Sparing Mechanism:

    • Most cells except neurons utilize fatty acids for energy to preserve glucose for CNS function.

Glycogenolysis

• Occurs in liver and skeletal muscle.

• Liver:

  • Glycogen breaks down into glucose-6-phosphate, which can be converted to glucose and released into the bloodstream.

• Skeletal Muscle:

  • Glycogen is split into glucose-6-phosphate, but lacks the enzyme to convert it into free glucose.

  • This glucose-6-phosphate undergoes glycolysis, producing pyruvate, which can either enter the Krebs cycle for ATP production or be converted to lactate and released into the blood.

Gluconeogenesis

• The liver uses several substrates for new glucose production: lactate, pyruvate, amino acids, and glycerol.

• Lactate from muscle glycogen breakdown is converted to pyruvate and then to glucose in the liver.

• Fat breakdown yields glycerol and fatty acids; glycerol enters the liver to generate glucose while fatty acids are utilized for energy.

• Protein breakdown yields amino acids, particularly alanine, which can also be transformed into glucose by first converting to alpha-keto acids and then into oxaloacetate or pyruvate.

Transition from Absorptive to Postabsorptive

• Transitioning occurs where proteins, triglycerides, and glycogen are mobilized for energy.

• Processes include:

  • Proteins being converted to amino acids and undergo gluconeogenesis.

  • Triglycerides being liberated into fatty acids and glycerol.

  • Overall energy transformation ensures glucose stays available primarily for the CNS.

Exam Type Questions

Question Type: Assess comprehension regarding fat and cholesterol roles in the blood and post-absorptive phases of metabolism.

Summary of Nutrient Metabolism during the Absorptive Period

1. Energy predominantly derived from carbohydrates post-meal.

2. Liver exhibits net uptake of glucose.

3. While some carbohydrates are stored as glycogen in liver and muscle, excess carbohydrate and fat are primarily stored as fat in adipose tissue.

4. Some protein synthesis occurs, with dietary amino acids also being utilized for energy or converted into fat.