Integration of Metabolism Flashcards
How is metabolism measure by?
- Oxygen uptake
- CO2 production
- Heat generation
- Energy
What are the main types of energy consumption for different tissues?
Muscle: 40% of body weight
- rely and carb and fat oxidation - May have period of high ATP demand
Brain and nervous: 2% of body but use 20% of resting metabolic rate because high continuous ATP demand
- Cannot use fats - Ketone bodies may be used partially substitute for glucose
Heart: 1% of body weight, 10% of resting metabolic rate
- Many mitochondria - Can use free fatty acid and ketone bodies (TCA substrates)
Liver: 2.5% of body, 20% RMR
- Main glycogen store and blood glucose source (glycogen depleted after 12-18h)
What is the function of the liver in metabolism?
- Immediate recipient of nutrients absorbed by intestines
- Can interconvert nutrient types
- Lipoprotein metabolism
- Site of glycolysis, gluconeogenesis, transamination
- Maintains blood glucose
Define gluconeogenesis?
Glucose from non carbohydrate sources e.g lactate, AA, glycerol, oxaloacetate (from TCA)
What is the blood sugar boundary for hypoglycemic coma?
- During fasting if Glu lower than 3mM body will go into hypoglycemic coma, to avoid this body can:
How does the body avoid hypoglycemic coma?
- Breakdown glycogen store
- Release free fatty acids from adipose tissue
- Convert acetyl CoA into ketone bodies via liver (fatty acids and ketone bodies can be used by muscle so more Glu available for brain)
What are the steps in gluconeogenesis?
- Oxaloacetate–>phosphophenolpyruvate
- Phosphophenolpyruvate carboxylase
- phosphophenolpyruvate–>fructose 1,6 bisphosphate
- fructose 1,6 bisphosphate—> fructose 6-phosphate
- fructose 6-phosphate–>glucose 6-p
- glucose 6-p–>glucose
- G-6 phosphate
What is the energy demand of gluconeogenesis?
6 ATP
How are proteins metabolized?
- AA feed into glycolysis/TCA as of pyruvate, acetyl CoA
- Ketone bodies can be stored, used in heart or brain
- AA backbones may be used for nucleotide production eg. NADPH
How are fats metabolized?
- fatty acid enter TCA as acetyl CoA (no pyruvate) and ketone bodies (from aceto-acetyl CoA)
- Some may generate AA
- Cannot convert fatty acids into glucose via gluconeogenesis (no net synthesis of oxaloacetate or pyruvate possible from acetyl CoA)
- Glycerol converted into DHAP for gluconeogenesis
How is increased Glucose demand met for?
- increased number of glucose transporters
- Muscle stores of glycogen are broken down to produce ATP
What are functions of adrenalin?
- Increases muscle glycolysis –> move ATP produced
- Increased gluconeogenesis as ATP demand increase and needs not met by blood glucose alone
- occurs in liver and moves into blood for transport into other tissues
- Increased fatty acid release –> move fatty acid available for ATP generation
Where in a pathway can metabolic control happen?
- Strongly dependent on enzyme activity
- Early on in pathway
- Unique step in pathway (increases ability to regulate activity through pathway)
- Irreversible
How are metabolic pathways controlled?
- Product inhibition (activate/inhibit enzyme)
- Hormones
- External signaling molecules relaying information from other pathways
Where is Hexokinase found?
Liver
Differentiate between the two hexokinases in terms of: glucose affinity, speed, at which glucose concentration they have their maximum activity, and G6P inhibition sensitivity
Hexokinase 1:
- in muscle there is high glucose affinity
- Rises rapidly in response to glucose concentration
- Maximum activity at low glucose concentration so operates at max velocity at all times
- Highly sensitive to G6P inhibition (if it accumulates is inhibited under anaerobic conditions)
Hexokinase 4:
- In liver low glucose affinity
- Higher Km at 4mM
- Converts glucose into G6P when available
- Reaction is slower in liver at same glucose concentration
- Less sensitive to blood glucose and G6P so can accumulate but reaction continues
What occurs during diabetes?
- Disorder of insulin release and signaling
- Glucose not taken up because problem in signaling pathway
What is the role of the Islets of Langerhans?
- make insulin, glucagon, somatostatin and pancreatic polypeptide
What are the roles of insulin, glucagon and glucocorticoids?
Insulin: stimulates uptake and use of Glu as storage
Glucagon: stimulates gluconeogenesis and glycogen and fat breakdown
- Major site of action is liver - Pancreatic hormone
Glucocorticoids: increases synthesis of metabolic enzymes concerning glucose availability
- Released by adrenals
What are some complications of diabetes?
- Hyperglycemia can damage tissues progressively
- Increased plasma fatty acid and LPs - possible CV complications
- Increased ketone bodies - possible acidosis
- Hypoglycemia - possible coma if insulin dose not controlled
How can diabetes be exasperated?
- Triglyceride in adipose tissue broken down - glycerol used in gluconeogenesis exacerbates condition
- Free fatty acid feed into beta oxidation produce ketone bodies –> excessive production–> diabetic ketoacidosis
How does insulin affect HK4 and G6Pase?
Insulin increases HK4 and decreases G6Pase activity so increases storage activity
What happens right after a meal?
Islets of Langerhans inc insulin, decreases glucagon secretion
- Liver: increased glucose uptake for glycogen synthesis and glycolysis
- Muscle: increased glucose uptake and glycogen synthesis
- Adipose: increased triglyceride synthesis
- Increased usage of metabolic intermediates throughout body because general stimulatory effect on synthesis and growth
How does glucose regulate glucagon?
- Transported into alpha cells via glucose transporters causing increased ATP
- ATP acts as signaling molecule to many ion channels leading to inhibition of glucagon release and insulin release
- Enhances beta cell communication and function
