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Gastrointestinal > Carbohydrate Metabolism & Glucose Homeostasis > Flashcards

Carbohydrate Metabolism & Glucose Homeostasis Flashcards

1
Q

Describe carbohydrates in the Western diet

A
  • Half the daily energy requirement
  • Starch= polysaccharide= 160g/day
  • Sucrose= disaccharide= 120g/day
  • Lactose= disaccharide= 30g/day
  • Glucose= monosaccharide= 10g/day
  • Free glucose and glycogen unimportant, all convertible to glucose, no essential dietary sugars
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2
Q

Describe the structure of glucose

A
  • In solution or combined with other sugars, almost entirely in a ring structure= pyranose ring (formed by a link between carbon-5 and carbon-1)
  • Linkage between one sugar and another can involve bond on carbon-1
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3
Q

Describe starch

A
  • Amylose (10 to 20%) and amylopectin
  • Amylose= linking glucose units between C1 and C4, alpha, straight chains
  • Amylopectin= straight chains with alpha 1-4 links with branches (carbon-1 of one sugar at the end of the chain is linked to C6 of another)
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4
Q

What are the enzymes involved in starch digestion?

A

a-Amylase
Glucoamylase
Isomaltase
=All general alpha-glucosidases (hydrolyse alpha-links)

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5
Q

Describe a-Amylase

A
  • Present in saliva – levels variable (controlled by the number of salivary amylase genes expressed)
  • also secreted by the pancreas into the duodenum
  • endoglycosidase: hydrolyses a(1-4) links
  • products are oligosaccharides
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6
Q

Describe Glucoamylase

A

present on luminal side of intestinal wall
exoglycosidase: hydrolyses a(1-4) links
in oligosaccharides, trisaccharide, maltose

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7
Q

Describe Isomaltase

A 
present on luminal side of intestinal wall
hydrolyses a(1-6) link in isomaltose
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8
Q

Describe a-glucosidase inhibitors

A
  • Interest in diabetes
  • Maitake fungus
  • Miglitol, Voglibose, Acarbose
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9
Q

What are the dietary disaccharides (intestinal)?

A
  • Maltose= contains alpha 1-4 link (hydrolysed by glucosamylase)
  • Isomaltose= alpha 1-6 links from the branch points hydrolysed by Isomaltase
  • Lactose= galactose linked beta 1-4 to glucose (cannot be hydrolysed by amylase so lactase or beta-galactosidase)
  • Sucrose= glucose and fructose, linked alpha 1-2, sucrase- if in blood, stomach ulcer
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10
Q

Describe artificial sweeteners

A
  • Mimic sucrose

- Sucralose= hydroxyl groups replaced by chlorides, cannot be hydrolysed by sucrase

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11
Q

What is roughage?

A
  • Non hydrolysable polysaccharides in the diet
  • Plant polysaccharides
  • Can be degraded by some extent by bacterial enzymes
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12
Q

Describe the uptake of glucose from the intestine

A
  • Secondary active transport
  • Sodium, potassium ATPase on basolateral face, hydrolyses ATP and uses the energy to create gradients of concentration
  • Sodium ions out into plasma
  • Symporter catalyses the uptake of glucose (up gradient) with 2Na+ (down gradient)
  • Uniporter GLUT-2 into plasma
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13
Q

Treatment for diarrhoea

A
  • Oral rehydration therapy
  • Combat loss of water by increasing concentration of sodium ions
  • Glucose and salt
  • Glucose promotes sodium ion uptake so expands plasma and retrieves water
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14
Q

What are the types of glucose transporters?

A
  • GLUT1= erythrocytes, placenta and brain
  • GLUT2= liver, kidney, intestine and pancreas= uptake increases as glucose rises
  • GLUT3= brain and testis= constant uptake rate
  • GLUT4= muscle, adipose, heart= insulin-responsive
  • GLUT5= jejunum= fructose specific
  • SGLT1= duodenum, jejunum, kidney= symporter, high affinity, low capacity
  • SGLT2= kidney= symporter, low affinity, high capacity
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15
Q

Describe glucose phosphorylation in the liver

A
  • Phosphorylated on C6 by phosphate from ATP (glucose-6-phosphate), catalysed by hexokinase (low Km for glucose) in most tissues
  • Liver contains glucokinase, high Km so less saturated
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16
Q

What are the metabolic fates of glucose?

A
  • G-6-P in liver or muscles converted into glycogen (isomerization of G6P to G-1-P, transfer by reaction with UTP to UDP-glucose)
  • Glycolytic breakdown= G6P to pyruvate/ lactate
  • Pentose-phosphate pathway= G6P to 5 carbon sugars and reduced coenzymes
17
Q

What is glycogen?

A
  • Polymer of glucose, chains linked alpha 1-4 with occasional alpha 1-6 branches
  • Carbon 4 free= non-reducing end, free carbon 1= reducing end
  • Glucose hydrolysed off or added at non-reducing end
  • Non-reducing end attached to glycogenin protein
18
Q

Describe hormonal control of glycogen metabolism

A
  • Glucose phosphorylated by glucokinase in liver/ hexokinase in muscle
  • Isomerized to glucose-6-phosphate, reacts with UTP, releasing pyrophosphate= UDP-glucose
  • Adds glucose units onto non-reducing ends to extend glycogen chains
  • Branching enzyme makes new branches when chains too long
  • Glycogen synthase transfers glucose from UDP-glucose to glycogen, activated by insulin
  • Glycogen breakdown = phosphate splits off one glucose unit at a time from non-reducing ends forming glucose 1-phosphate (glycogen phosphorylase- adrenaline and glucagon)
19
Q

Describe glycolysis

A
  • G-6-P
  • Isomerised to fructose-6-phosphate
  • Phosphorylated to fructose bisphosphate, catalysed by phosphofructokinase
  • Fructose bisphosphate split into 2 3-carbon phospho-sugars (interconvertible)
  • Each oxidised, generate 2 molecules of ATP, catalysed by glyceraldehyde phosphate dehydrogenase
  • Reduces NAD to NADH and incorporates phosphate into this intermediate, bisphosphoglycerate, which can transfer a phosphate to ADP and form ATP
  • Phosphoenolpyruvate= conversion to pyruvate forms ATP
20
Q

Describe gluconeogenesis

A

-Liver and kidney only
-Irreversible step between phosphoenolpyruvate and pyruvate = pyruvate kinase reaction reversed by sidestepping
=pyruvate to oxaloacetate
=oxaloacetate to phosphoenolpyruvate
-Some irreversible steps reversed by hydrolysing inorganic phosphate off

21
Q

What are the precursors of glucose in gluconeogenesis?

A
  • Lactate from anaerobic glucose metabolism
  • Glycerol from breakdown of triacylglycerol (acetyl CoA cannot be converted to glucose so fat cannot be converted to glucose)
  • Glucogenic amino acids
22
Q

Describe the Pentose-phosphate pathway

A

Glucose degradation

  • Production of reduced coenzyme NADPH, function in reductive biosynthetic pathways/ anti-oxidative
  • G6P oxidised to 6-phosphogluconate (NADP to NADPH), which is oxidised by different dehydrogenase= 5 carbon sugar (ribulose 5 phosphate) and CO2
23
Q

Describe carbon shuttling reactions

A
  • More 5C sugars made than needed so regenerate 6C sugars
  • Transketolase (take 2 carbons from one sugar) to make a 3C and 7C
  • Transaldolase (moves 3 carbons from 7C)
24
Q

What is Stoichiometry?

A

Glucose is oxidised, reduced NADP is produced, products can be shuttled around to make 6C and 3C sugars

25
Q

What is the anti-oxidant function of glutathione?

A
  • Lipid peroxidation a hazard in red blood cells transporting oxygen
  • Peroxides reduced by tripeptide called glutathione (3 amino acids, cysteine has sulfhydryl group) to hydroxy-compounds
  • Glutathione oxidised to disulphide in process by reduced NADP
26
Q

Describe G6PDH deficiency

A
  • the commonest genetic disorder in human
  • > 400 mutations known
  • X-linked, so usually affect males
  • G6PDH has low (but not zero) activity
  • exacerbated by anti-malarial drugs, some antibiotics, broad beans
  • GSH deficiency in erythrocytes leads to haemoglobin crosslinking- red blood cells undergo haemolysis
27
Q

Describe metabolism of fructose

A
  • Fructose phosphorylated by hexokinase
  • Or fructokinase in liver, phosphorylates to fructose-1-phosphate
  • Glycolysis like pathway
  • Deficiency in fructose 1-phosphate aldolase= build up of fructose-1-phosphate= fructose intolerance= inhibits glycogen breakdown, oxidative phosphorylation and gluconeogenesis= hypoglycaemia and lactic acidaemia
28
Q

Describe metabolism of galactose

A

-Liver
-Galactokinase= galactose-1-phosphate
-Epimerized to glucose 1-phosphate by first being transferred to UDP and then an epimerase, acting on UDP-galactose and converting it to UDP-glucose
-Deficiency of kinase/ transferase that transfers galactose to UDP leads to galactosaemia
=galactose 1-phosphate accumulates in liver= hepatomegaly and jaundice, affects lens causing swelling and cataracts

29
Q

Describe alcohol metabolism

A
  • Absorbed in stomach
  • Alcohol dehydrogenase in gastric cells
  • Ethanol oxidised by NAD ethanal (acetaldehyde) then to ethanoic acid (acetic acid)
  • Convertible to acetyl-CoA so precursor to fatty acids and ketones
  • Oxidised in tricarboxylic acid cycle; aldehyde dehydrogenase (one isomer in mitochondria and low Km value, other in cytoplasm with Km)
  • Mutation in mitochondrial aldehyde dehydrogenase inactivates it so alcohol oxidation builds up high concentration of ethanal= nausea
  • Drug called disulfiram or Antabuse inhibits aldehyde dehydrogenase= aversion therapy for alcohol addiction
30
Q

Describe metabolism of toxic alcohols

A
  • Methanol yields formaldehyde, reacts with nucleic acids
  • Ethylene glycol (anti-freeze) to glyoxal to oxalic acid, precipitates calcium in kidneys
  • Fomepizole drug= inhibitor of alcohol dehydrogenase

Gastrointestinal (48 decks)

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