Energy storage Flashcards
tissues that have an absolute requirement for glucose as an energy source
- red blood cells
- neurtrophils
- innermost cells of kidney medulla
- lens of eye
what is glycogen
highly branched polymer of glucose residues linked together by α1-4 and α1-6 glycosidic bonds in 10:1 ratio
structure of glycogen
- highly branched structure (α1-6 bonds form branch points) provides many sites where glucose can be added or removed so rapid synthesis and degradation
- large molecule so many glucose molecules stored with minimal osmotic effect in the tissue
- highly polar molecule that attracts a lot of water
major energy stores in a 70kg man
- triacylglycerols 15kg
- glycogen 0.4 kg
- muscle protein 6kg
how is glycogen stored
granules
glycogen in liver vs muscle
liver
- ~100g glycogen
- G6P converted to glucose and exported to blood
- buffer of blood glucose levels
muscle
- ~300g glycogen
- lacks glucose-6-phosphatase enzyme
- G6P enters glycolysis for energy production for muscle
glycogenesis (glycogen synthesis)
- glucose + ATP → glucose-6P + ADP hexokinase (glucokinase in liver)
- glucose-6P ↔ glucose-1P phosphoglucomutase
- glucose-1P + UTP + H2O → UDP-glucose + Pi G1P uridyltransferase
- glycogen (n) + UDP-glucose → glycogen (n+1) + UDP glycogen synthase(α 1-4 glycosidic bonds) or branching enzyme(α 1-6 glycosidic bonds)
what is UTP
- structurally similar and energetically equivalent to ATP
- UDP-glucose considered highly activated form of glucose
- important intermediate in synthesis of sugar-containing molecules
when does glycogenolysis occur
- in skeletal muscle in response to exercise
- in liver in response to fasting or stress
glycogenolysis (glycogen degradation)
- glycogen (n) + Pi → glucose-1P + glycogen (n-1) glycogen phosphorylase (α 1-4 glycosdic bonds) or de-branching enzyme (α 1-6 glycosidic bonds)
- glucose-1P ↔ glucose-6P phosphoglucomutase
in muscle, glucose-6P enters glycolysis for energy production - in liver: glucose-6P + H2O → glucose + Pi glucose-6-phosphatase
in liver, glucose released into blood and transported to tissues
how is glycogen metabolism regulated
- controlling activities of rate limiting enzymes (glycogen synthase and glycogen phosphorylase)
- allosteric control
- covalent modification in response to hormone levels (reversible phosphorylation)
- enzymes controlled reciprocally
allosteric control of glycogen metabolism
AMP activates muscle glycogen phospphorylase but not liver form
hormonal regulation of glycogen metabolism
glucagon and adrenaline increase phosphorylation of enzymes
- glycogen synthase inhibited
- glycogen phosphorylase activated
insulin increases dephosphorylation of enzymes
- glycogen synthase activated
- glycogen phosphorylase inhibited
glycogen storage diseases
- inherited diseases
- arise from deficiency or dysfunction of enzymes in glycogen metabolism
- severity depends on which enzyme/tissues is affected
- 12 distinct types
clinical consequences of glycogen storage diseases
- excess glycogen storage causes tissue damage
- diminished glycogen stores cause hypoglycaemia and poor exercise tolerance
- liver and/or muscle are affected
- glycogen structure may be abnormal
2 examples of glycogen storage diseases
- von Gierke’s disease - glucose-6-phosphate deficiency
- McArdle disease - muscle glycogen phosphorylase deficiency
time course of glucose utilisation
- glucose from food ~2 hours
- glycogenolysis 8-10 hours
- gluconeogenesis 8-10 hours onwards
where does gluconeogenesis occur
- liver
- kidney cortex (lesser extent)
precursors of gluconeogenesis
- lactate from anaerobic glycolysis in exercising muscle and RBC (Cori cycle)
- glycerol released from adipose tissue breakdown of triglycerides
- amino acids mainly alanine and those whose metabolism involves pyruvate
- acetyl Co-A can’t be converted to glucose because the PDH reaction is irreversible
gluconeogenesis
irreversible steps 1, 3 and 10 of glycolysis are bypassed by thermodynamically spontaneous reactions
10.pyruvate + ATP + CO2 → oxaloacetate + ADP + Pi pyruvate carboxylase
oxaloacetate + GTP → phosphoenolpyruvate + GDP + CO2 PEPCK
3.fructose-1,6-bisphosphate + H2O → fructose-6-phosphate + Pi fructose 1,6-bisphosphatase
1.glucose-6-phosphate + H2O → glucose + Pi glucose-6-phosphatase
regulation of gluconeogenesis
glucagon, cortisol stimulates gluconeogenesis
- increased amount of PEPCK
- increased amount and activity of fructose 1,6-bisphosphatase
insulin inhibits gluconeogenesis
- decereased amount of PEPCK
- decreased amount and activity of fructose 1,6-bisphosphotase
insulin:glucagon determines rate of gluconeogenesis
triacylglycerols
- highly efficient energy store
- energy intake in excess of requirements converted to TAGs for storage
- TAGs are hydrophobic so stored in anhydrous form in adipose tissue
- utilised in prolonged exercise, stress, starvation, pregnancy
- storage under hormonal control (promoted by insulin and reduced by glucagon, adrenaline, cortisol, GH, thyroxine)
adipocytes
- ~0.1mm in diameter
- cells expand as more fat added
- average adult has ~30 billion fat cells wieghing 15kg
- increase in size about fourfold before dividing and increasing number of cells
- don’t lose adipocytes on weight loss
overview of dietary triacylglycerol metabolism
- TAG → fatty acids + glycerol by pancreatic lipase in small intestine
- reform into TAGs in intestinal epithelial cell and packaged into chylomicron
- chylomicrons drain into lacteal system which drains into lymphatic system
- chylomicrons into bloodstream via thoracic duct
- TAGs either stored in adipose tissue or utilised by tissues
- TAG in adipose broken down by hormone sensitive lipase and fatty acids transported from adipose to tissues bound to albumin
- fatty acid oxidation for energy in tissues
what is fatty acid synthesis (lipogenesis)
fatty acids are synthesised from acetyl-CoA (drived from catabolism of carbohydrates and amino acids) using ATP and NADPH
liver lipogenesis
- NADPH produced in cytoplasm from pentose phosphate pathway
- glucose → pyruvate in cytoplasm (glycolysis)
- pyruvate enters mitochondria and forms acetyl-CoA + oxaloacetate which condense to form citrate (TCA cycle)
- citrate cleaved in cytoplasm releasing acetyl-CoA and oxaloacetate
- oxaloacetate converted back to pyruvate, making NADPH in process
- acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA (3C)
- fatty acid synthase complex builds fatty acids by sequential addition of 2 carbon units provided by malonyl-CoA with loss of CO2
regulation of liver lipogenesis
allosteric regulation of acetyl-CoA carboxylase
- citrate activates
- AMP inhibits
hormonal regulation of acetyl-CoA carboxylase
- insulin activates by dephosphorylating enzyme
- glucagon and adrenaline inhibit by phosphorylating enzyme
lipolysis (fat mobilisation)
- hormone senstive lipase breaks down TAGs in adipose tissue to release glycerol and fatty acids into blood
- glycerol travels to liver and used for gluconeogenesis
- fatty acids travel bound to albumin to mucscle and other tissues for β oxidation
regulation of lipolysis
- glucagon and adrenaline lead to phosphorylation and activation of hormone-sensitive lipase
- insulin leads to dephosphorylation and inhibition of hormone-sensitive lipase
why is it beneficial for degradative (catabolic) and biosynthetic (anabolic) pathways to have different routes
- greater flexibility - substrates and intermediates can be different
- better control - can be controlled independently or co-ordinately
- thermodynamically irreversible steps can be by-passed
fatty acid oxidation VS fatty acid synthesis
fatty acid oxidation (β oxidation)
- cycle of reactions that remove C2
- C2 atoms removed as acetyl CoA
- produces acetyl CoA
- occurs in mitochondria
- separate enzymes in mitochondrial matrix
- oxidative - produces NADH and FADH2
- requires small amount of ATP to activate fatty acid
- intermediates linked to CoA
- regulated indirectly by availability of fatty acids in mitochondria
- glucagon and adrenaline stimulate
- insulin inhibits
fatty acid synthesis
- cycle of reactions that add C2
- C2 atoms added as malonyl CoA
- consumes acetyl CoA
- occurs in cytoplasm
- multi-enzyme complex in cytoplasm
- reductive - requires NADPH
- requires large amount of ATP to drive process
- intermediates linked to fatty acid synthase by carrier protein
- regulated directly by acetyl-CoA carboxylase activity
- glucagon and adrenaline stimulate
- insulin stimulates
