Integration of Metabolism Flashcards
Metabolic features of the brain
Requires continuous supply Cannot metabolise fatty acids Ketone bodies can partially substitute Too little glucose (hypoglycemia) faintness and coma Too much glucose (hyperglycemia) irreversible damage for retina
Metabolic features of tissue
ATP depending on exercise Reliant on carbohydrate and fatty acid oxidation Light contraction - OxPhos Vigorous contraction - 02 becomes limiting factor, glycogen breakdown and lactate formation
Metabolic features of heart
Aerobic respiration - mitochondria Can use TCA cycle substrate - free fatty acids, keton bodies
Metabolic features of tissues
Wide repertoire of metabolic process Highly metabolic Maintaining blood glucose Glucose storage organ Lipoprotein metabolism Transport of triglycerides and cholesterol
Metabolic features of adipose tissue
Long term storage site for fatty acids in the form of triglycerides
Glycolysis
Excess glucose-6-phosphate can be used to generate glycogen
Excess Acetyl CoA can generate fatty acids
During fasting acetyl CoA results in ketone body production rather than TCA cycle
Glucose-6-phosphate undergos pentose phosphate pathway which generates the bulk of NADPH
How do avoid a hypoglycaemic coma
Breakdown of liver glycogen
Release free fatty acids
Convert acetyl CoA into ketone bodies via the liver
Gluconeogenesis
Lactate generated by skeletal muscle which can be taken up by the liver and using lactate dehydrogenase
Amino acids can be from diet or from skeletal muscles
Glycerol backbone used genertes dihydroxyyacetone phosphate DHAP
Red arrows indicate which key steps must be bypassed
What are the irreversible reactions of glycolysis
Kinase hexokinase
Phosphofructokinase
Pyruvate kinase
Bypass reactions of gluconeogenesis
It is not energetically favourable
Additional high energy bonds required
Overview of glycolysis
Can fatty acids be converted into glucose by gluconeogenesis
No
Instead they can be converted into ketone bodies
Aerobic respiration
Increase in glucose demands result in increase in the number of glucose transporters
Increase in requirement of muscle actomyosin ATPase and cation balance
Adrenalin plays a key role: increase glugoneogenesis, glycolysis and release of fatty acids
Anaerobic respiration
To replenish NAD+ levels and maintain glycolysis, pyruvate is taken up by the liver and converted in lactate
Lactate is then used to generate glucose by gluconeogenesis
How do we control metabolic pathways
Centred around irreversible steps
Can be by product inhibition
Under influence of signalling molecules such as hormones
What is the michaelis constant
Km which is the concentration of substrate which an enzyme functions at half-maximal rate
What does a low Km mean for hexokinase 1 (found in muscle)
Active at low concentrations and operating at maximal velocity
Highly sensitive to inhibition of glucose-6-phosphate
When TCA stops accumalates glucose-6-phosphate
What does a higher Km in Hexokinase 4 meane (found in liver)
Less sensitive to blodo glucose concentrations and less sensitive to inhibitory effects of glucose 6 phosphate
Glucose 6-phosphatase can catalyse the reverse reaction
When is insulin secreted
Blood glucose levels rise
When is glucagon released
Glucose levels fall
When is adrenalin released
Strong and fast metabolic effects to mobilise fight or flight
When are glucocorticoids used
Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability
What effect does having a meal have
Increase glucose uptake by liver used for glycogen and glycolysis (acetyl coa used for fatty acid synthesis
Increase glucose uptake and glycogen synthesis
Increased triglyceride synthesis in adipose tissue
Increase usage of metabolic intermediates due to general stimulatory effect
After a meal what happens
Blood glucose falls
Increased glucagon secretion
Glucose production in liver results from glycogen breakdown and gluconeogenesis
Utilisation of fatty acid breakdown as alternative substrate
