Metabolic regulation Flashcards
Definitions - nutrition, nutrients, macronutrients, micronutrients
- Nutrition - “The process by which a living organism assimilates food and uses it for growth, liberation of energy, and replacement of tissues”
- Nutrients are “… components of food which have recognisable functions in the body”
- Essential nutrients cannot be made by the body
- Macronutrients – Carbohydrates, fats, proteins
- Micronutrients – Vitamins, minerals, trace elements and anything else
Nutrients, Food and Diet
- The chemical structure of a food affects the way nutrients are handled in the body
- Different nutrients complement each other
- full range of nutrients needed for a “balanced diet”
- Inadequate or “unbalanced” diet ! clinical deficiency
- compromising physiological function or causing disease
Carbohydrate Metabolism: The challenge for the body
- Glucose is essential fuel for life – Brain cells need glucose
- High glucose is toxic to cells – Damage to microvasculature
- The challenge: maintain glucose at 5mM
Meeting the challenge
• Mechanisms for storing and creating glucose
– Liver = critical organ
• Very tight regulation
– Insulin and Glucagon key hormonal regulators
Glucose metabolism in the Liver
- first interaction is glucose transport via glut2 transporter which has a high affinity for glucose. Then glucose is phosphorylated. liver then stores it as glycogen which can be metabolised to glucose to exit cell
- high blood levels of glucose leads to increased production of glycogen. In low glucose more glycogen is converted to glucose
- insulin is a key regulating hormone. Stimulates glycogen synthesis. stimulates glycolysis.
- fasting leads to high levels of glucagon
Glucose Metabolism in the Muscle
glucose enters via GLUT4. converted to glycogen. Muscle cannot break down g6p into glycogen.
Converted to CO2 via TCA cycle
Insulin stimulates glucose uptake
GLUT4 is found inside cell and moves when insulin stimulates the cell adrenaline and contraction have a big impact on glycogen
Glucose Metabolism Summary
• During the fed state the main purpose of energy homeostasis is to store calories
• Insulin is the major effector of this
• Insulin leads to:
– Glucose stored as glycogen (muscle & liver)
– Glucose as fuel in muscle
– Glucose carbons (& calories) stored in fatty acids
• Insulin also switches off Glycogen degradation and gluconeogenesis
Lipid Metabolism in Liver
- in a fasting state glucagon simulates cpt-1 (b oxidation)
- Alot of malonyl CoA prevents b oxidation. indirect regulation by insulin so alot of insulin leads to alot of malonyl CoA. More lipogenesis occurs
Lipid metabolism in muscle
- fatty acids form majority of fuel for muscle contraction
- important regulators are contraction and adrenaline
Lipid Metabolism in Adipose Tissue
- insulin is a strong down regulator
- in some rodents glucagon is a strong regulator but has less effect in humans
- fatty acids can circulate to reach muscle or liver
Lipid Metabolism - Summary
• During the fed state lipids are produced & stored
• Insulin is the major effector of this
• Insulin leads to:
– Glucose ! Fatty acids
– Fatty acid storage in adipose
• Adrenergic stimulation mobilises fatty acids in the fasting state
– Fatty acids become major fuel source for muscle
Protein Metabolism Summary
• During the fed state excess amino acids are deaminated
• During fasting amino acids a major source of glucose (gluconeogenesis)
• Glucagon is the major effector of this
• Glucagon in the liver leads to:
– Increased uptake, deamination and urea cycle activity
Integrated Metabolism - 1
• The liver: central regulator of metabolism
• The brain: actively consumes glucose and O2, • ~20% of daily energy expenditure
• The kidney: ~10% of daily energy expenditure; • filter ~ 800 litres of blood a day: 200 litres of filtrate
!~ 2 litres of urine
• Muscle:
• skeletal muscle - occasional burst of intense (anaerobic)activity;
• cardiac and smooth muscle are aerobic and continuous
• Fat: a long term energy store; brown fat has an important thermogenic role
Integrated Metabolism - 2
- Metabolic specialisation of organs and tissues arises from differential gene expression.
- Each system has its particular set of enzymes and transporters.
- This is the top level of metabolic regulation.
Principles of Metabolic Regulation - How is control achieved?
• Metabolic specialisation
• Change in protein number (expression/degradation)
– Slow but effective adaptation to prolonged environmental change
• Changing the activities of existing molecules
– activity of proteins can be changed quickly (milliseconds to minutes)
– covalent modification, allosteric interactions or both
