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Medicine Year 2 > Endocrine Topic 3 - CHO Metabolism > Flashcards

Endocrine Topic 3 - CHO Metabolism Flashcards

1
Q

Why is gluconeogenesis important?

A

Vital when fasting (e.g. when sleeping) to maintain glucose supply to glucose-dependent tissues - brain, RBC etc.

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2
Q

How does GLUT4 function?

A
  • Not normally on cell surface - in vesicles
  • Insulin stimulates movement and fusion of vesicles with plasma membrane - increased glucose uptake by cell
  • Low insulin, endocytosis of vesicles, less GLUT4 on surface, reduced glucose uptake by cell
  • In adipose and muscle, more glucose transported in and converted to triglycerides/glycogen when blood glucose concentration rises after a meal
  • GLUT4 moves to membrane in muscle in response to exercise - increased glucose in cells for ATP production
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3
Q

Describe the action of insulin

A
  • Binds to tyrosine kinase receptor found mostly in liver, striated muscle, adipocytes and hypothalamus
  • Causes phosphorylation of intracellular part of receptor
  • Insulin receptor substrate protein binds, activates protein kinase B (Akt)
  • Akt stimulates - glucose transport, glycogen synthesis, fatty acid synthesis
  • Akt inhibits - lipolysis, gluconeogenesis
  • Signalling cascade amplifies signal
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4
Q

Describe the action of glucagon

A
  • Binds to G-protein coupled glucagon receptor (on cell surface)
  • Activates enzyme, stimulate second messengers e.g. cAMP - stimulates protein kinase A
  • Increases gluconeogenesis (liver) and glycogenolysis
  • Decreases glycogenesis
  • No effect on uptake by tissues - no receptors
  • Adrenaline + glucocorticoids have the same effect
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5
Q

What factors contribute to plasma glucose concentration?

A
  • Increased by:
    • Glucose from diet
    • Gluconeogenesis by the liver
    • Glycogenolysis by the liver
  • Decreased by
    • Synthesis of pentoses (5 carbon) e.g. DNA, RNA
    • Synthesis of fatty acids and triglycerides from acetyl coA after glycolysis
    • Uptake by tissues (muscle, adipose)
    • Conversion into glycogen in muscles and liver
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6
Q

List the uses of glucose in cells

A
  • Produce ATP - glycolysis, TCA cycle, oxidative phosphorylation
  • Storage as glycogen - glycogenesis (especially in liver/muscle)
  • Storage as lipid - lipogenesis
  • Synthesis of sugars - pentose phosphate pathway
  • Small amount of synthesis of glycolipids and glycoproteins
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7
Q

Which glucose transporters are most important metabolically?

A

GLUT 2 and 4

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8
Q

Describe the normal range for plasma glucose concentration

A

Fasted = 4-5 mM

After meal = up to 8-12 mM

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9
Q

How is cellulose digested?

A

Can’t be digested - don’t have enzymes to cleave beta 1-4 bonds

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10
Q

In what form are carbohydrates absorbed?

A

As monosaccarides

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11
Q

Why doesn’t glycogenolysis occur in muscles?

A

They don’t have glucose-6-phosphatase

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12
Q

How does insulin affect the enzymes involved with muscle glycogen metabolism?

A

Increased glycogen synthase, increased GLUT4

Decreased glycogen phosphorylase

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13
Q

Describe the stages of carbohydrate digestion

A
  • Mouth - salivary amylase
    • Breaks starch down into dextrins (+ some maltose, few glucose)
  • Exocrine pancreas - pancreatic alpha-amylase
    • Breaks down dextrins into maltose
  • Intestine - maltases, lactases, sucrases
    • Maltases break down maltose to glucose
    • Lactases break down lactose to glucose and galactose
    • Sucrases break down sucrose to fructose and glucose
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14
Q

Describe the process of gluconeogenesis

A
  • Reversal of glycolysis
  • Have to bypass 3 irreversible steps, mediated by glucokinase, phosphofructokinase and pyruvate kinase (use ATP)
  • Glucokinase bypassed by glucose-6-phosphatase (mostly in liver)
  • PFK bypassed by fructose-1,6-biphosphatase
  • Pyruvate kinase bypassed by phosphenolpyruvatecarboxylase (PEPCK) and pyruvate carboxylase (PCOX)
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15
Q

What is the effect of alcohol on blood glucose concentration?

A

Alcohol lowers blood glucose concentration

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16
Q

Describe the structure of disaccharides

A
  • Sucrose = glucose-fructose by an alpha 1-2 glycosidic bond
  • Lactose = galactose-glucose by beta glycosidic bond
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17
Q

List the types of carbohydrate in the diet

A
  • Polysaccharides - lots of monosaccharides in a chain e.g. starch, cellulose
  • Disaccharides - 2 x monosaccharides e.g. maltose (2 glucose), sucrose (glucose + fructose), lactose (glucose + galactose)
  • Monosaccharides - glucose, fructose, galactose
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18
Q

How does glucagon affect the enzymes involved with muscle glycogen metabolism?

A

Decreased GLUT4, decreased glycogen synthase

Increased glycogen phosphorylase

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19
Q

List the glucose transporters and their mechanisms of action

A
  • GLUT 1 - 5
    • Down concentration gradient by facilitated diffusion
  • SGLT 1 + 2
    • Sodium-linked, against concentration gradient using co-transportation with sodium (active transport)
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20
Q

What is required for glucose-6-phosphatase/PEPCK action?

A
  • Stored in ER - need transporters for substrates/products
  • Expression stimulated by adrenaline, glucocorticoids
  • Suppressed by insulin
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21
Q

What is the first step whenever glucose is transported into a cell?

A
  • Conversion of glucose to glucose-6-phosphate by hexokinases I-IV
    • Traps glucose in the cell - no transporters for glucose-6-phosphate
    • Maintains concentration gradient
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22
Q

How are carbohydrates transported and stored?

A

Transpored as glucose

Stored as glycogen in liver, muscle and adipose tissue

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23
Q

Why is C peptide measured clinically?

A

Released during insulin production, used as surrogate marker for insulin as it is more stable

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24
Q

How do the SGLT transporters function?

A
  • Na+/K+ ATPase creates high Na+ concentration outside cell (requires ATP)
  • Use high Na+ to pump glucose in
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25
Q

Describe the structure of glycogen

A

Polyglucose - alpha 1-4 and alpha 1-6 bonds

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26
Q

What is the overall reaction which occurs in glycolysis?

A

Glucose + 2ADP + 2Pi + 2NAD+ –> 2 pyruvate + 2ATP + 2NADH + 4H+

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27
Q

Describe the structure of polysaccharides

A
  • Starch = glucose-glucose-glucose-… by alpha 1-4 glycosidic bond
  • Cellulose = glucose-glucose-glucose-… by beta 1-4 glycosidic bonds
28
Q

Define gluconeogenesis

A

Synthesis of glucose de novo from substrate other than carbohydrate by the liver (+ kidney in starvation?) to buffer plasma glucose

29
Q

How is insulin synthesised?

A
  • Peptide hormone, synthesised as pro-hormone
  • Preproinsulin –> proinsulin –> insulin
  • Preproinsulin - long peptide, A, B + C chains, matures in vesicles, oxidised to give cysteine residues with sulphur covalently bonded
  • Proinsulin - loses C chain to become insulin
30
Q

Give examples of slowly digested starches

A
  • Trapped in intact granules/plant cell wall structure - raw cereals/vegetables
  • Resistant to amylase (tight 3D structure) - processed foods or raw/cold potatoes
  • Dietary fibre - slow digestion/absorption as gut contents viscous - beans/legumes
  • High fat content - delayed gastric emptying
31
Q

Define glycaemic index

A

How long equal amounts of carbohydrate from a particular source take to be digested/absorbed compared with glucose

32
Q

How does insulin affect the enzymes involved with liver glycogen metabolism?

A
  • Increased glycogen synthase, increased glucokinase
  • Fed - decreased G6Pase, decreased glycogen phosphorylase
33
Q

Where are SGLT 1 and 2 found?

A
  • SGLT1 - intestinal mucosa, co-transports glucose/galactose with sodium ions from the gut lumen
  • SGLT2 - kidney tubules, co-transports glucose/galactose with sodium ions from the filtrate
34
Q

Describe the process of glycogenesis

A
  • Glucose –> G6P by glucokinase
  • G6P–> G1P by phosphoglucomutase
  • G1P –> UDP glucose by glucose-1-phosphate uridyltransferase
  • UDP glucose –> glycogen by glycogen synthase (UDP released)
    • Glycogen synthase is very highly regulated - insulin target
35
Q

How is galactose metabolised?

A

Galactose –> glucose-1-phosphate –> glucose-6-phosphate

36
Q

Describe stimulus-secretion coupling in pancreatic beta cells

A
  1. High blood glucose concentration
  2. Concentration gradient causes glucose to move into beta cell through GLUT2
  3. Glucokinase phosphorylates glucose to G6P
  4. G6P used to generate ATP
  5. High ATP inhibits ATP sensitive K+ channel in cell membrane, closes, cell depolarised
  6. L-type voltage-gated Ca2+ channels open - Ca2+ influx
  7. Ca2+ influx causes vesicles with insulin to fuse with cell membrane and release insulin
37
Q

How is glycaemic index calculated?

A

(Area under graph for 50g carb over 2 hours / area under curve for 50g glucose) x 100

38
Q

Describe the structure of monosaccharides

A
  • 6 carbons, C6H12O6
  • L (not found naturally) or D, alpha or beta
    • Alpha - -OH group below C1 atom
    • Beta - -OH group above C1 atom
39
Q

Describe the hormonal regulation of gluconeogenesis

A
  • Glucagon/adrenaline/glucocorticoids
    • Decrease glucokinase, increase G6P and PEPCK
  • Insulin
    • Increase glucokinase, decreased G6P and PEPCK
40
Q

How does glucagon affect the enzymes involved with liver glycogen metabolism?

A
  • Increased G6Pase and glycogen phosphorylase
  • Fasted - decreased glucokinase and glycogen synthase
41
Q

How is glucagon synthesised?

A
  • Peptide hormone, synthesised as pro-hormones
  • Secreted as polyglucagon - long peptide
  • Cleaved to give smaller peptide e.g. glucagon in alpha cells of pancreas cells
  • In intestinal cells (L cells) cleaved to give GLP1/2
  • Degraded very quickly - liver is only tissue which responds, hepatocytes are only cells with receptors
42
Q

What is the function of ATP?

A

ATP is hydrolysed to ADP + phosphate, releasing energy for anabolic processes

43
Q

What can be used to produce glucose via gluconeogenesis?

A

Lactate, pyruvate (from glycolysis), glycerol (from triglyceride breakdown), some amino acids

44
Q

When does gluconeogenesis occur?

A

After 4.5 hours liver glycogen store is used

45
Q

What causes MODY?

A

Mutation in glucokinase - insulin in beta cells not secreted

46
Q

How is blood glucose concentration regulated?

A

Insulin (lowers b.g.) and glucagon (raises b.g.)

47
Q

How is pyruvate used in aerobic respiration?

A
  • Converted to acetyl coA by pyruvate dehydrogenase, produced CO2 and NADH
  • Acetyl coA used in TCA cycle
48
Q

Which transporters are not involved in fructose transport?

A

SGLT 1/2, GLUT1, GLUT3

49
Q

What is the function of the pentose phosphate pathway?

A
  • Synthesis of fatty acids and nucleotides (RNA, DNA)
  • Dehydrogenation of G6P is committent step
50
Q

Describe the citric acid cycle

A
  • 8 reactions, mitochondrial
  • Produces 3NADH, FADH2, GTP, CoA and 2CO2
  • Oxaloacetate and acetyl coA –> citrate –> isocitrate –> alpha-ketoglutarate –> succinyl coA –> succinate –> fumarate –> L-malate –> oxaloacetate
  • NADH gives 3 ATP, FADH2 gives 2 ATP, GTP gives 1 ATP
  • Aerobic total = 36 ATP
51
Q

What is the function of glucokinase?

A

Low affinity, good for sensing glucose level (with GLUT2)

52
Q

What can starch be broken down into?

A

Dextrose, maltose or glucose

53
Q

What is the function of phosphofructokinase?

A
  • Converts fructose-6-phosphate to fructose-1,6-biphosphate
  • Inhibited by negative feedback from ATP, citrate
  • Determines whether glucose-6-phosphate is used for glycolysis or other purposes
54
Q

Which tissues are carbohydrate dependent? Why?

A
  • Red blood cells - no mitochondria
  • Brain - blood-brain barrier
  • Brown adipose tissue - thermogenesis
  • Testes - blood-testes barrier
55
Q

How is glucagon secreted?

A

Less well understood than insulin secretion, in response to low blood glucose concentration

56
Q

Where are GLUT1-4 found? What are their functions?

A
  • GLUT1 - widespread, transports glucose and galactose, high affinity
  • GLUT2 - Liver, pancreatic beta cells, small intestine, kidney
    • Transports glucose, galactose and fructose
    • Low affinity, high capacity
  • GLUT3 - CNS, placenta, testes
    • Transpots glucose (high affinity) and galactose
    • Primary glucose transporter for neurons
  • GLUT4 - skeletal/cardiac muscle and adipocytes
    • Insulin responsive glucose transporter (high affinity)
  • GLUT5 - small intestine, sperm
    • Transports fructose (not glucose/galactose)
57
Q

What is the function of glycogen?

A
  • Stored form of glucose, only enough stored for a few seconds
  • In the liver, glycogen is converted back to glucose and released into the blood
  • In muscles, glycogen is used by the muscle itself to make ATP
58
Q

How is pyruvate used in anaerobic respiration?

A

Converted to lactate (NADH –> NAD+​) by lactate dehydrogenase

59
Q

Describe the process of glycogenolysis

A
  • Glycogen –> glucose-1-phosphate by glycogen phosphorylase (phosphate released)
  • Glucose-1-phosphate –> G6P by phosphoglucomutase (reversible step)
  • G6P continues in glycolysis
60
Q

Which foods have high/low glycaemic index?

A

High = glucose, low = beans

Pulses < fruit < cereals

61
Q

Describe the process of glycolysis

A
  • Glucose –> glucose-6-phosphate by glucokinase
  • Glucose-6-phosphate –> fructose-6-phosphate
  • Fructose-6-phosphate –> fructose-1-phosphate by fructokinase (DHAP and glyceraldehyde-3-phospate are intermediates)
  • Fructose-1-phosphate –> Fructose-1,6-biphosphate by phosphofructokinase
  • Fructose-6-phosphate –> –>–> phosphoenol-pyruvate
  • Phosphoenol-pyruvate –> pyruvate by pyruvate kinase
62
Q

How does stimulation of gluconeogenesis occur?

A
  • By glucagon/adrenaline
  • Low glucokinase, high glucose-6-phosphatase and PEPCK
  • Effect at level of gene expression - takes time
63
Q

Where does ATP come from?

A
  • Creatinine phosphate (in muscle, short term)
  • Anaerobic metabolism - carbohydrate broken down to lactate
  • Aerobic metabolism of carbohydrate, fat or protein (in mitochondria)
64
Q

Where are hexokinase I-IV found?

A
  • Hexokinase I-III - all tissues, inhibited by G6P (negative feedback)
  • Glucokinase (hexokinase IV) - pancreatic beta cells and liver
65
Q

How is the balance between glycogenolysis and glycogenesis maintained?

A
  • Glycogenesis and glycogenolysis don’t occur at the same time
  • Enzymes are highly regulated, reciprocally

Medicine Year 2 (41 decks)

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