Integration of Metabolism Flashcards
What fuel sources do muscles rely on during vigorous contraction
Carbohydrates and fatty acid oxidation
How much of resting metabolic rate is used by the brain and nervous tissue, despite making up 2% of body weight What fuel source can it utilise
20% Glucose only, ketone bodies partially
What % of body weight do these tissues make up: Muscle Brain and nervous tissue Adipose tissue Heart Liver
Muscle 40% Brain and nervous tissue 2% Adipose tissue 15% Heart 1% Liver 2.5%
What % of resting metabolic rate is made up by a) liver b) heart
A 20% B 10%
During fasting, what is the fate of much of the Acetyl CoA produced
Ketone body formation (rather than entering the tca cycle)
What other molecules can be produced from Peruvate and TCA cycle intermediates
Amino acids Backbones can be used to make nucleotides
What pathway does glucose-6-phosphate enter for nucleotide production What is generated in bulk by this pathway
Pentose phosphate pathway NADPH for anabolic pathways eg cholesterol synthesis
What happens if plasma glucose conc falls below 3mM, eg during fasting
Hypoglycaemic coma
What does the body do to avoid hypoglycaemia
Breakdown of liver glycogen stores Release of free fatty acids from adipose tissue Convert Acetyl CoA into ketone bodies via the liver
How many hours does it take to typically exhaust glycogen stores
12-18 hrs
What is the overall aim of gluconeogenesis What precursors enter this pathway
Generate glucose from pyruvate Non carbohydrate precursors eg lactate, some amino acids and glycerol form pyruvate, oxaloacetate and DHAP respectively
What is the fate of lactate in the liver
Converted into pyruvate by lactate dehydrogenase (LDH), aka the Cori Cycle
What is the glycerol backbone used to generate in times of starvation
Dihydroxyacetone phosphate (DHAP) Also made in step 5 of glycolysis
What steps in the gluconeogenesis pathway are bypassed by non-glycolytic enzymes
Pyruvate(3C) to oxaloacetate (4C) Oxaloacetate(4C) to phosphoenol pyruvate (3C) Fructose-1,6-bisphosphate (6C) to fructose-6-phosphate (6C) Glucose-6-phosphate to glucose
Why do three reactions have to be bypassed in gluconeogenesis
Glycolysis has 3 irreversible reactions catalysed by hexokinase, phosphofructokinase and pyruvate kinase. Gluconeogenesis is therefore not a simple reversal of glycolysis as these 3 reactions have to be bypassed
Where does gluconeogenesis occur
In the cytoplasm, APART FROM first reaction (pyruvate to oxaloacetate, catalysed by pyruvate carboxylase)
How many atp molecules are used up in gluconeogenesis and why
4 ATP Needed to make the reaction energetically favourable
What type of amino acids can give rise to glucose via gluconeogenesis following deamination What type of amino acids can be used to synthesise fatty acids and ketone bodies
Glucogenic Ketogenic
Why can’t fatty acids be converted into glucose
In the TCA cycle, oxaloacetate is eventually regenerated so no net synthesis of oxaloacetate or pyruvate is possible from Acetyl CoA
What 3 enzymes require ATPduring muscle contraction
Muscle actomyosin ATPase Ca2+ATPase Na+K+ATPase for cation balance
What role does Adrenalin play in meeting ATP demand
Increases rate of glycolysis in muscle and gluconeogenesis in liver Increases release of fatty acids from adipocytes
How does the body respond to an increased demand for ATP, eg during aerobic exercise
Increases number of glucose transporters on membranes of muscle cells Adrenalin
How does the body respond when transport of glucose cannot be matched by demand during a aerobic exercise
Increased breakdown of muscle glycogen Liver uses lactate to form glucose (recovery)
Name two methods of control of metabolic pathways
Product inhibition Signalling molecules eg hormones
What is the difference between the isoforms of hexokinase
They are maximally active at different concentrations of glucose They have a different Michaelis constant (Km) - conc of substrate at which an enzyme functions at a half-maximal rate (Vmax)
How does muscle Hk differ from Liver Hk
Muscle Hk (Hk I): High glucose affinity (Km of 0.1mM) High sensitivity to glucose 6 phosphate inhibition Liver Hk (Hk IV): Low glucose affinity (Km of 4mM) Less sensitive to G6P inhibition
What enzyme in the liver catalysed the reverse reaction to hexokinase
Glucose-6-phosphatase
What are glucocorticoids
Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability
How does insulin affect the body
Secreted from islets of pancreas Increased glucose uptake by liver - used for glycogenesis and glycolysis (Acetyl CoA needed for fatty acid synthesis) Increased glucose uptake and glycogenesis in muscle Increased triglyceride synthesis in adipose tissue Increased usage of metabolic intermediates (due to general stimulatory effect on body’s synth and growth)
How does the body respond to falling blood glucose levels
Inc glucagon and red insulin secretion Glucose production in liver from glycogenolysis and gluconeogenesis Fatty acids breakdown utilised for atp production (preserves glucose for brain) (Similar to adrenaline)
How does the body react to prolonged fasting (longer than can be covered by glycogen reserves)
Glucagon/insulin ratio increases further Adipose tissue hydrolysed triglycerides to provide fatty acids for metabolism Tca cycle intermediates reduced to provide substrates for gluconeogenesis Protein breakdown provides aa substrates for gluconeogenesis Ketone bodies produced from fa and as in liver to partially substitute brains glucose req
In what condition is metabolism controlled as if the body is undergoing starvation
Diabetes Mellitus (Both B cell dysfunction and insulin resistance)
What are some complications of diabetes
Hyperglycaemia with progressive tissue damage (eg retina, kidney, peripheral nerves) Increase in plasma fatty acids and lipoprotein levels, with possible cardiovascular complications Increase in ketone bodies with risk of acidosis Hypoglycaemia with coma if insulin dosage is I perfectly controlled
How does insulin deficiency and relative excess of glucagon affect the liver
Increased hepatic output of glucose and thus, hyperglycaemia
