Overview of Metabolism

Introduction to Metabolism

• energy metabolism- the way the body stores & utilizes energy

• influenced by 4 things

  • eating patterns
  • growth
  • stress
  • metabolic rate

• endocrine signals control whether the body stores or uses energy

• hormones have coordinated regulation of metabolic pathways to maintain adequate energy supplies for all body cells

  Two Critical Concepts Driving the Control of Energy Metabolism

  1. The body has to store nutrients during intake periods & break down these stores between intake periods because food intake is intermittent
  2. Blood glucose levels need to be maintained at all times because the brain depends on glucose as its main energy source

Energy Balance

• Energy input- sourced from carbs, fat, protein
• energy output in six forms:
  • mechanical work
  • muscle contraction
  • movement of cells, organelles, & appendages
  • synthetic reactions
  • fuel storage
  • tissue building
  • creation of essential functional molecules
  • membrane transport
  • minerals
  • organic anions/cations
  • amino acids
  • signal generation/conduction
  • electrical
  • chemical
  • mechanical
  • heat production
  • temperature regulation
  • inefficient chemical reactions
  • detoxification & degradation
  • urea formation
  • conjugation
  • oxidation
  • reduction
• Main formulas
  • input + production = utilization + output
  • energy input = energy utilization + energy output
  • energy input = work performed + heat released (energy output)
• endocrine system is responsible for making sure that a steady supply of small nutrients is always available to cells for their energy demands
  • replenishes the supply in 2 main ways
  • absorption of more nutrients into the bloodstream
  • mobilization of energy stores

Body Composition of an Average Human

• by body weight
  • 65% water & minerals
  • 20% fat
  • 14% protein
  • half is fixed- can’t be used for energy because it’s used a structure for organs/tissues
  • half is mobilizable- can be used for energy
  • 0.6% carbohydrates
• in caloric stores
  • 76% fat
  • 23% protein
  • 1% carbohydrates

Fuel Metabolism

• important organ/tissue contributors
  • liver
  • adipose tissue
  • muscle
• blood glucose level- should be between 90-120 mg/dL
  • important to maintain for brain, nervous tissue, & RBCs
• metabolic processes
  • glycogenesis- formation of glycogen from glucose
  • glycogenolysis- breakdown of glycogen to make glucose
  • gluconeogenesis- formation of glucose from other compounds like fatty acids or proteins
  • lipogenesis- formation of lipids from FFAs (free fatty acids)
  • lipolysis- breakdown of lipids to FFAs
  • protein synthesis- synthesis of proteins from amino acids
  • proteolysis- breakdown of protein to amino acids

Metabolic States

• absorptive/fed state- period immediately after eating when nutrients absorbed through intestinal wall into the circulatory & lymphatic systems (about 4 hours after each meal)
  • focused on energy storage
  • glycogenesis occurs
  • increased lipogenesis, & protein synthesis
  • decreased gluconeogenesis & lipolysis
  • insulin high
• postabsorptive/fasting state- period after the absorptive state has finished where blood glucose levels are maintained by converting other molecules to glucose
  • usually in late morning, afternoon, and night if person is eating on a regular 3-meal schedule
  • lower blood glucose and glucose production
  • insulin low
  • hepatic glycogenolysis & gluconeogenesis
  • muscle glycogenolysis
  • blood glucose maintained by liver
  • important for uptake/utilization in non-insulin sensitive tissues (brain & central nervous system)

Regulation of Absorptive and Post-Absorptive Metabolism

• metabolic changes in the transition between absorptive & postabsorptive states triggered by endocrine signals
• 4 important hormones
  • insulin
  • made by beta cells in pancreas
  • associated with energy storage
  • glucagon
  • made by alpha cells in pancreas
  • associated with maintaining blood glucose levels
  • epinephrine
  • made in adrenal medulla
  • associated with maintaining blood glucose levels
  • cortisol
  • made in adrenal cortex
  • associated with maintaining blood glucose levels
• mechanism of hormone action
  • hormones bind to receptors that trigger a cascade that brings about the final response
  • receptors are large proteins specific to hormones
  • protein hormones receptors in PM
  • steroid hormone receptors in cytoplasm
  • thyroid hormone receptors in nucleus
  • receptor number at target tissue determines the response of the target cell to a hormone

Anatomy of Pancreas

• only 1-2 % of pancreas is actually used for endocrine functions

  • rest is used for producing digestive enzymes

    

Actions of Insulin

• insulin lowers blood glucose

  • increases glucose uptake by activating the GLUT4 Transporter
  • increases glycogenesis
  • decreases glycogenolysis

• lowers blood amino acids

  • increased amino acid uptake
  • increased protein synthesis

• lowers blood free fatty acids

  • increased FFA uptake & lipogenesis
  • inhibit lipase activity

• mechanism of action for insulin

  • insulin molecule binds to receptor in the cell membrane
  • activates insulin signal pathway
  • a vesicle containing the GLUT4 transporter is sent to the PM
  • once the vesicle is fused with the PM, glucose is transported inside the cell

• insulin secretion increases as blood glucose increases & vice versa

  

Glucagon

• secreted by alpha cells of pancreas
• major actions- increase glycogenolysis, gluconeogenesis, lipolysis
• primary regulation of release- decreased blood glucose

Adrenal Gland

• cortex is 80-90%

  • androgens (50% of androgens in women) made in reticularis
  • cortisol made in fasiculata
  • aldosterone made in glomerulosa

• medulla is 10-20%

  • catecholamines (norepinephrine & epinephrine) are made here

  

Cortisol

Regulation of Cortisol Secretion

• stress, hypoglycemia, or morning time positively regulates the release of corticotropin releasing hormone (CRH) from the hypothalamus

  • nighttime negatively regulates the release of corticotropin

• CRH from the hypothalamus causes the pituitary gland to release adrenocorticotropin hormone (ACTH)

• ACTH stimulates the adrenal glands to produce cortisol

  

Actions of Cortisol

• primary effects all meant to maintain blood glucose levels
• primary effects are
  • mobilizing amino acids from protein in muscle
  • stimulating hepatic gluconeogenesis
  • facilitate lipolysis by epinephrine
  • anti-insulin effect on muscle & adipose tissue
  • opposes glucose uptake