MetabolismTom Ransom
Division of Endocrinology and Metabolism
October 19. 2017
Relationships with commercial interests:
Grants/research support: Research trials: Principal/Sub Investigator, CDHA, Endocrinology Research, Centre for Clinical
Research. Sanofi, Astra Zenica, BMS, Merck, Sepracor, Pfizer, Servier, Lilly, Abbott, GSK,
Novartis, Novo Nordisk
Speaker’s bureau/honoraria: Speaking honoraria: Sanofi, Astra Zenica, BMS, Merck, Sepracor, Pfizer, Servier, Lilly, Abbott,
GSK, Novartis, Novo Nordisk
Consulting fees: Advisory Boards: Merck & Co., Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Valeant
Other:
Conflicts of Interest
Outline
• Define
• Basal metabolic rate/energy expenditure
• Hormones and Metabolism
• Discusion
Wiktionary, the free dictionary 5,369,740 entries with English definitions from over 3,650 languages
• metabolism
• Etymology
• From French métabolisme, from Ancient Greek μεταβολή (metabolḗ, “change”), from μετά (metá, “meta-”) + βάλλω (bállō, “I throw”).
• pronunciation[edit]
• IPA(key): /məˈtæbəlɪzəm/
• Noun
• metabolism (countable and uncountable, plural metabolisms)
• 1.(physiology) The complete set of chemical reactions that occur in living cells.
ATP is the currency
Kreb’s Cycle
Food is the Fuel
Bomb Calorimetry
Atwater numbers
• Think caloric density• 1 gram protein = 4 kcal
• 1 gram CHO = 4 kcal
• 1 gram fat = 9 kcal
• 1 gram EtOH = 7 kcal
• 3500 kcal = 1 pound
One calorie is the amount of energy required to raise one gram of water one degree Celsius at sea level
Which meal has more calories?
Diet Induced Thermogenesis
Effects of Exerciseon Metabolic Rate
• Exercise dramatically increases metabolic rate
• Rate remains elevated for extended period afterwards (excess post-exercise O2consumption)• Duration depends on intensity of exercise
• Long-term exercise may elevate resting metabolic rate (RMR)
Speakman JR, et al: Proc Nutr Soc 2003; 62(3):621-34.
15
Glycogen
Associated with lots of water
Carbohydrate Loading
Carbohydrate Depletion (dehydration)
Weight change during a triathlon
TABLE 1. Body weights (kg) and changes in body weight (kg) of triathletes competing in the 2000 South African Ironman triathlon*** P < 0.0001. From: Sharwood: Clin J Sport Med, Volume 12(6).November 2002.391-399
Hitting the Wall
40 seconds tops
Communication in the Body
• “Electrical” – Nervous System • “Signals” - Hormonal
Hormone
• Greek hormao (to arouse or excite)
• Substance that is secreted into the circulation by endocrine glands and acts as a chemical effector in other tissues• May stimulate or supress
Types of hormones
• Classically a hormone is secreted into the blood and acts on distant tissues, e.g. IGF-1 (insulin-like growth factor) produced from the liver
• Paracrine – act within the same tissue, e.g. testosterone stimulates spematogenesis in the adjacent seminiferous tubules.
• Autocrine – act within the same cell, e.g. prostaglandins from adipocytes influence adipocyte growth
• Those secreted from nerve endings, e.g. ADH (antidiuretic hormone)
Hormone structure
• Steroids – cortisol, estradiol
• Proteins - insulin
• Tyrosine (an amino acid) derivatives – thyroid hormones and catocholamines
Hormone structure• Steroids and thyroid hormones are fat soluble and
diffuse across cell membranes to bind intracellular receptors• In order to be “soluble” in blood they require carrier
proteins, i.e binding globulins
• Protein hormones and catacholamines are water soluble and require cell surface receptors and elicit their effects through second messangers• Most protein hormones have binding globulins as well
Hormone levels vary as a function of age
2
0 20 40 60 80
Age (years)
Testo
ste
rone (
mg/d
)
4
6
8
Morley JE, et al. Metabolism 1997
Seasonal variations of hormones
Monthly variations
Daily variations
Pulsatility over the day
Pulsatility from minute to minute
The Pituitary is the Master Gland
Who is this?
36
Sample feedback loop
Hyperprolactinemia
This woman presented with carpal tunnel syndrome
An elderly gentleman presents with confusion and weight loss
Simple Approach to Endocrinopathies
• If a hormone is lacking replace it
• If there is too much of a hormone suppress it chemically or surgically