Carb Metabolism Flashcards

1
Q

Normal vs critical blood glucose?

A
Normal = 4-5mM
Critical = 2.5mM
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2
Q

Symptoms of hypoglycaemia?

A
Muscle weakness
Loss of coordination
Mental confusion
Sweating
Hypoglycaemic coma and death
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3
Q

Symptoms of hyperglycaemia?

A

Non enzymatic modification of proteins:
-cataracts,
-lipoproteins vital in atherosclerosis
Hyperosmolar coma

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4
Q

Role of pentose-phosphate pathway?

A

producing nucleotides + NADPH

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5
Q

How can body maintain blood glucose over a range of activities?

A

brain cells + 🔴 only use glucose

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6
Q

How body deals with excess blood glucose?

A

Glycogen synthesis
Pentose phosphate pathway
FA synthesis

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7
Q

How body deals with lack of blood glucose?

A

Glycogen breakdown

Gluconeogenesis

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8
Q

Describe structure of glycogen?

A
  • Branched polymer of D-glucose

- Mostly alpha 1-4 linked, but also alpha 1-6 linked

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9
Q

Role of protein glycogenin?

A

acts as a primer allowing initiation of glycogen synthesis

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10
Q

Effect of glycogen storage diseases?

A

suffer from muscular/neurological disorders

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11
Q

Describe glycogen synthesis

A

-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

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12
Q

Role of glycogenin?

A

reacts with UDP-glucose + catalyses addition of 1st glucose then acts as a substrate for glycogen synthase

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13
Q

Why glycogen?

A
  • 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
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14
Q

Debranching enzymes

A
  • Transferase activity moves last glucose residues to non-reducing end of an existing chain
  • Glucosidase removes the 1-6 link releasing glucose
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15
Q

Role of transferase?

A

debanching enzyme that moves last glucose residues to non-reducing end of an existing chain

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16
Q

Role of glucosidase?

A

debranching enzyme that removes the 1-6 link releasing glucose

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17
Q

Enzymes that breakdown glycogen?

A

Phosphorylase
Transferase
Debranching enzyme (glucosidase)
Phosphoglucomutase

18
Q

Enzymes needed to form glucose?

A
Phosphorylase
Transferase
Debranching enzyme (glucosidase)
Phosphoglucomutase 
Glucose 6 phosphatase
19
Q

Role of phosphorylase?

A

breaks the a1-4 links to break units individually giving glucose-1-phosphate
Transferase
Debranching enzyme a1-6

20
Q

Role of phosphoglucomutase?

A

converts G1P to G6P

21
Q

Fate of G6P?

A

Muscle : used to ATP synthesis

Liver : converts into glucose since contains glucose 6 phosphatase

22
Q

Describe structure of glycogen phosphorylase

A
  • 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
23
Q

Role of glycogen phosphorylase?

A

-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.

24
Q

Role of phosphorylase b kinase?

A

glycogen phosphorylase b (inactive) -> active

transfers a phosphate from an ATP to 1 serine residue on each phosphorylase subunit

25
Q

Describe hormonal regulation of glycogenolysis

A
  • Insulin inhibits
  • Glucagon stimulates in liver
  • Adrenaline stimulates in muscle
  • Cortisol is a weak stimulus
26
Q

Describe activation of phosphorylase

A

-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

27
Q

Describe control of glycogen phosphorylase in muscle

A

-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.

28
Q

Describe control of glycogen phosphorylase in liver

A
  • glycogen breakdown by phosphorylase inhibited by glucose

- even after enzyme activated to phosphorylase a form by being phosphorylated

29
Q

Describe activation of phosphorylase b kinase by Ca2+ in muscle?

A
  • 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
30
Q

Describe activation of phosphorylase b kinase by Ca2+ in liver?

A

-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

31
Q

When’s glycogen synthase activated?

A

When plenty glucose

  • by ATP + G6P
  • by dephosphorylation (by protein phosphatase-1)
32
Q

When’s glycogen phosphorylase activated?

A

When glucose is in short supply

-by phosphorylation (by phosphorylase b)

33
Q

When’s glycogen synthase inactivated?

A

by phosphorylation (by PKA)

34
Q

When’s glycogen phosphorylase inactivated?

A
  • by ATP and G6P

- by dephosphorylation (by protein phosphatase-1)

35
Q

What’s pentose phosphate pathway?

A
  • 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
36
Q

Daily glucose requirement + brain?

A

160g + brain needs 120g

37
Q

Total body reserve for glucose?

A

210g

38
Q

Role of gluconeogenic pathway?

A
  • Converts pyruvate-> glucose

- In liver + little in kidney but during starvation kidney productions rises to 40%

39
Q

Vital substrates for gluconeogenesis?

A

AA(alanine), lactate, glycerol

40
Q

Role of glucose 6-phosphatase?

A

G6P -> glucose in liver (+ kidney) can reverse

hexokinase

41
Q

Role of oxaloacetate?

A

mitochondrial molecule while pyruvate synthesised in cytosol so pyruvate carrier