Metabolism and Signaling in Organisms

Integration of Metabolism

• Metabolism is the sum of all chemical reactions in an organism.
• The diagram depicts the integration of metabolic pathways in various tissues of the body.
• The liver is central to processing macronutrients, synthesizing and distributing lipids, ketone bodies, and glucose, as well as converting excess nitrogen to urea.
• The pancreas secretes insulin and glucagon in response to blood glucose fluctuations.
• The small intestine absorbs nutrients which are then transported to the liver via the portal vein.
• The brain maintains its membrane potential by transporting ions. It integrates environmental and bodily inputs, sending signals to other organs.
• Cardiac muscle utilizes ATP aerobically to pump blood.
• Lymphatic system carries lipids to the liver.
• Adipose tissue synthesizes, stores, and mobilizes triacylglycerols. Brown adipose tissue is involved in thermogenesis.
• Skeletal muscle uses ATP aerobically or anaerobically for mechanical work.

Pathways of Carbohydrate, Amino Acid, Nucleotide, and Lipid Metabolism

• Different metabolic pathways are illustrated in various figures.
• Pathways for carbohydrate catabolism, including glycogenolysis, glycolysis, and lactic acid fermentation, are detailed.
• Anabolic pathways like gluconeogenesis, glycogen synthesis, and amino acid/nucleotide synthesis, along with details of intermediary metabolism.
• Fat pathways including β-oxidation of fatty acids, fatty acid synthesis, triacylglycerol synthesis, and ketone body formation, are described.

Metabolism at the Whole Organism Level

• Cellular-level metabolism focuses on specific enzymes, pathway fluxes, and feedback regulations across organelles.
• Whole-organism level metabolism focuses on organ roles and structures, and the flux of metabolites from organ to organ. Hormonal regulation of metabolism and control of body mass are examined.

Neuronal Versus Hormonal Signaling

• Neuronal signaling: Nerve cells release neurotransmitters to nearby cells. Signaling distances are small (less than 1 mm).
• Hormonal signaling: Hormones are carried by the bloodstream to nearby or distant cells/organs. Signaling distances are large (1m or more).

Hormone-Receptor Interactions

• Different cell types have unique receptor sets.
• The same receptor can have varied downstream impacts in different cells.
• Similar hormones may bind different receptors.
• Hormone-receptor interactions are high-affinity, requiring only low hormone concentrations.
• Receptors can be located intracellularly or extracellularly. Specific examples of cell surface and nuclear receptors are described, along with mechanisms for hormonal action.

"Downstream" Events Following Hormone Binding

• A secondary messenger (e.g., cAMP, inositol triphosphate) is released inside the cell. This often alters enzyme activity.
• Receptor tyrosine kinases get activated.
• Hormone-gated ion channels open or close, changing membrane potential.
• Adhesion receptors send information to the cytoskeleton.
• Intracellular receptor proteins (hormone-receptor complexes) affect gene expression.

Three Classes of Mammalian Hormones

• Endocrine: Hormones released into the bloodstream reach target cells. Examples: insulin, glucagon.
• Paracrine: Hormones released into extracellular space act upon neighboring cells. Examples: eicosanoids.
• Autocrine: Hormones affect the cell where they are produced.

Peptide and Amine Hormones

• Peptide hormones (e.g., insulin, glucagon) bind to extracellular receptors.
• Extracellular binding triggers signal amplification via second messengers. This affects a wide variety of target tissues.
• Examples of peptide hormones include insulin, glucagon, somatostatin, and epinephrine.

Insulin is a Peptide Hormone

• Insulin is a peptide hormone synthesized in the pancreas.
• Preproinsulin is processed into the active 5.8 kDa insulin molecule.
• Insulin has 51 amino acids, with similar A and B chains in humans, pigs, and cows.

Newer Insulins

• Rapid-acting insulin analogs (Lispro, Aspart, Glulisine) have a faster onset than regular insulin.
• Long-acting insulin analogs (Glargine, Detemir) have a longer duration of action.

Epinephrine and Norepinephrine

• Epinephrine and norepinephrine are catecholamine hormones synthesized in the adrenal medulla from tyrosine.
• These hormones are stored in vesicles and released like peptide hormones.
• They bind to extracellular receptors and generate secondary messengers.

Paracrine Hormones

• Paracrine hormones (e.g., prostaglandins, thromboxanes, leukotrienes) act locally.
• They are produced from arachidonic acid via phospholipase A2 and respond to external stimuli.

Steroid Hormones

• Steroid hormones (e.g., testosterone, estradiol, cortisol) are derived from cholesterol.
• They bind to carrier proteins in the bloodstream.
• Steroid hormones enter target cells, bind to intracellular receptors, and alter gene expression.

Retinoid Hormones

• Retinoid hormones derive from vitamin A (retinol).
• They bind to nuclear receptors and impact cell growth and differentiation.

Thyroid Hormones

• Thyroid hormones (T3 and T4) bind to nuclear receptors and regulate gene expression.
• T3 has 3 iodine atoms, and T4 has 4.
• Deficiency in Iodine leads to Goiter.

Nitric Oxide

• Nitric oxide (NO) is a molecule produced from arginine.
• It acts locally and increases intracellular cGMP via guanylyl cyclase.

Major Endocrine Glands

• The diagram shows the hypothalamic-pituitary axis, thyroid, parathyroids, adrenals, pancreas, ovaries/testes, and adipose tissue.

Top-Down Versus Bottom-Up Hormonal Signaling

• Top-down: Brain signals to the body (e.g., oxytocin, vasopressin, cortisol).
• Bottom-up: Other body parts signal to the brain (e.g., epinephrine, insulin, leptin).

Hormones and Their Target Tissues

• The diagram shows the interconnected hormonal signaling pathways with their primary, secondary, and ultimate tissue targets.

Tissue-Specific Metabolism and Division of Labor

• Different tissues have specialized metabolic functions.
• The diagram demonstrates this division of labor among various tissues (brain, liver, pancreas, heart, adipose tissue, small intestine, etc.).

Muscle Metabolism

• Muscle stores limited glycogen (1-2% of mass).
• Muscle activity can be aerobic (using oxygen) or anaerobic (without oxygen).

Cori Cycle

• The Cori Cycle is an example of metabolic cooperation between muscle and liver.
• Muscle uses anaerobic glycolysis to produce lactate.
• The liver converts lactate back into glucose via gluconeogenesis during recovery.

Brain Metabolism

• The brain primarily utilizes glucose and ketone bodies for energy.
• The brain lacks large-scale glycogen stores.
• The brain actively uses ATP via Na+/K+ ATPase for action potentials.

The Well-Fed State

• High blood insulin, low glucagon during the well-fed state.
• The liver synthesizes and stores glycogen. Triglycerides are also stored in adipose tissue.

The Fasting State

• Occurs between meals.
• In the fasting state, glycogenolysis happens.
• If fasting continues, gluconeogenesis is the major source of glucose for the body.

Diabetes Mellitus

• Diabetes mellitus involves impaired insulin function and leads to metabolic consequences like hyperglycemia, ketone body buildup, and further complications from protein breakdown.

New Anti-diabetic Agents

• Various medications and insulin analogs are now available to help manage diabetes.

Leptin and the Fat Hormones

• Adipose tissue produces leptin, which signals to the hypothalamus about energy reserves.
• Leptin suppresses appetite and increases metabolism.
• Leptin deficiency can lead to obesity.

Nutrition

• Quantitative and qualitative needs of the diet for health.
• Various factors that influence energy expenditure and dietary needs (basal metabolic rate, thermogenic effect, physical activity, environment).

Nutritional Quality of Proteins

• All essential amino acids must be present simultaneously for protein synthesis.
• Animal proteins often have higher biological value than plant proteins, often because of their amino acid content.

Vitamin Facts

• A variety of vitamins and their roles in metabolism.

Explore the essential concepts of metabolism and signaling at the whole organism level. This quiz covers the roles of neurotransmitters and hormones in metabolic activities and the interactions between different organs. Assess your understanding of these biological processes.