Carb Metabolism Flashcards
Normal vs critical blood glucose?
Normal = 4-5mM Critical = 2.5mM
Symptoms of hypoglycaemia?
Muscle weakness Loss of coordination Mental confusion Sweating Hypoglycaemic coma and death
Symptoms of hyperglycaemia?
Non enzymatic modification of proteins:
-cataracts,
-lipoproteins vital in atherosclerosis
Hyperosmolar coma
Role of pentose-phosphate pathway?
producing nucleotides + NADPH
How can body maintain blood glucose over a range of activities?
brain cells + 🔴 only use glucose
How body deals with excess blood glucose?
Glycogen synthesis
Pentose phosphate pathway
FA synthesis
How body deals with lack of blood glucose?
Glycogen breakdown
Gluconeogenesis
Describe structure of glycogen?
- Branched polymer of D-glucose
- Mostly alpha 1-4 linked, but also alpha 1-6 linked
Role of protein glycogenin?
acts as a primer allowing initiation of glycogen synthesis
Effect of glycogen storage diseases?
suffer from muscular/neurological disorders
Describe glycogen synthesis
-G6P -> Glucose 1 phosphate via phosphoglucomutase
-G1P + UTP activating glucose
-forms UDP-Glucose.
-glycogenin + UDP-glucose
-catalyses addition of 1st glucose
-acts as substrate for glycogen synthase
-allows glycogen synthase to add on UDP-Glucose
to increase chain length
-when chain has 11 monomers of glucose, some of chain removed –> branch via branching enzyme
-forms alpha 1-6 links
Role of glycogenin?
reacts with UDP-glucose + catalyses addition of 1st glucose then acts as a substrate for glycogen synthase
Why glycogen?
- Cannot store glucose as it’s osmotically active
- 400mM glucose stored as 0.01mM glycogen
- Fat not mobilised as readily
- Fat cannot be used as an energy source in absence of oxygen
- Fat cannot be converted to glucose
Debranching enzymes
- Transferase activity moves last glucose residues to non-reducing end of an existing chain
- Glucosidase removes the 1-6 link releasing glucose
Role of transferase?
debanching enzyme that moves last glucose residues to non-reducing end of an existing chain
Role of glucosidase?
debranching enzyme that removes the 1-6 link releasing glucose
Enzymes that breakdown glycogen?
Phosphorylase
Transferase
Debranching enzyme (glucosidase)
Phosphoglucomutase
Enzymes needed to form glucose?
Phosphorylase Transferase Debranching enzyme (glucosidase) Phosphoglucomutase Glucose 6 phosphatase
Role of phosphorylase?
breaks the a1-4 links to break units individually giving glucose-1-phosphate
Transferase
Debranching enzyme a1-6
Role of phosphoglucomutase?
converts G1P to G6P
Fate of G6P?
Muscle : used to ATP synthesis
Liver : converts into glucose since contains glucose 6 phosphatase
Describe structure of glycogen phosphorylase
- Large multi-subunit enzyme
- Allosteric enzyme that has sites away from active site that control its activity by inducing shape changes in the protein + activated by phosphorylation but modulated by other factors
Role of glycogen phosphorylase?
-key enzyme in glycogenolysis + forms glucose-1-
phosphate
-many phosphorylase molecules bound to each glycogen particle so glycogenolysis switched on (less than a second in muscle)
-G6P formed provides fuel for muscles + in liver G6P is dephosphorylated (via glucose-6-phosphatase) + secreted into blood maintaining 5mmol/l blood sugar.
Role of phosphorylase b kinase?
glycogen phosphorylase b (inactive) -> active
transfers a phosphate from an ATP to 1 serine residue on each phosphorylase subunit
Describe hormonal regulation of glycogenolysis
- Insulin inhibits
- Glucagon stimulates in liver
- Adrenaline stimulates in muscle
- Cortisol is a weak stimulus
Describe activation of phosphorylase
-via cAMP cascade:
-NA/A binding to GPCR
-β-adrenergic receptor coupled to Gs
-adenylate cyclase
-synthesis of cAMP
-activates PKA
-PKA activates phosphorylase kinase
-phosphorylase kinase converts phosphorylase b -> phosphorylase a
-phosphorylase a cleaves G1P -> glycogen
-PKA also converts glycogen synthase a ->
glycogen synthase b
-glycogen synthase a (inactive) so synthesis of glycogen inactivated
-so synthesis + breakdown not occurring simultaneously
Describe control of glycogen phosphorylase in muscle
-glycogen phosphorylase b activated w/o
phosphorylation by 5’-AMP (which forms when ATP depleted, tells cell energy is needed)
-5’-AMP binds to nucleotide-binding site (allosteric)
-ATP binds to same site - blocking activation
-G6P also blocks 5´-AMP activation as sufficient energy in cell so more glucose isn’t needed.
Describe control of glycogen phosphorylase in liver
- glycogen breakdown by phosphorylase inhibited by glucose
- even after enzyme activated to phosphorylase a form by being phosphorylated
Describe activation of phosphorylase b kinase by Ca2+ in muscle?
- Ca2+ activate phosphorylase b kinase (allowing phosphorylation of phosphorylase b -> a
- allows mediation of glycogenolysis during muscle contraction
- as Ca2+ high in muscle contraction + so will be demand for energy
- to get max activity of glycogenolysis + phosphorylase b kinase, need both Ca2+ + phosphorylation
- allows body to regulate activity
Describe activation of phosphorylase b kinase by Ca2+ in liver?
-α-adrenergic activation stimulates Ca2+ release
-phosphorylase b kinase under dual regulation via 2 diff receptor types:
via cAMP elevation (–> PKA activation)
Ca2+ mediated via α-adrenergic/IP3 pathway
When’s glycogen synthase activated?
When plenty glucose
- by ATP + G6P
- by dephosphorylation (by protein phosphatase-1)
When’s glycogen phosphorylase activated?
When glucose is in short supply
-by phosphorylation (by phosphorylase b)
When’s glycogen synthase inactivated?
by phosphorylation (by PKA)
When’s glycogen phosphorylase inactivated?
- by ATP and G6P
- by dephosphorylation (by protein phosphatase-1)
What’s pentose phosphate pathway?
- Plenty glucose
- Always active (irrespective of excess glucose) as body requires nucleotides, coenzymes etc
- Produces NADPH - vital coenzyme in FA synthesis so aids fat synthesis
Daily glucose requirement + brain?
160g + brain needs 120g
Total body reserve for glucose?
210g
Role of gluconeogenic pathway?
- Converts pyruvate-> glucose
- In liver + little in kidney but during starvation kidney productions rises to 40%
Vital substrates for gluconeogenesis?
AA(alanine), lactate, glycerol
Role of glucose 6-phosphatase?
G6P -> glucose in liver (+ kidney) can reverse
hexokinase
Role of oxaloacetate?
mitochondrial molecule while pyruvate synthesised in cytosol so pyruvate carrier
