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
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
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)
4
Q
What are the enzymes involved in starch digestion?
A
a-Amylase
Glucoamylase
Isomaltase
=All general alpha-glucosidases (hydrolyse alpha-links)
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
6
Q
Describe Glucoamylase
A
present on luminal side of intestinal wall
exoglycosidase: hydrolyses a(1-4) links
in oligosaccharides, trisaccharide, maltose
7
Q
Describe Isomaltase
A
present on luminal side of intestinal wall hydrolyses a(1-6) link in isomaltose
8
Q
Describe a-glucosidase inhibitors
A
- Interest in diabetes
- Maitake fungus
- Miglitol, Voglibose, Acarbose
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
10
Q
Describe artificial sweeteners
A
- Mimic sucrose
- Sucralose= hydroxyl groups replaced by chlorides, cannot be hydrolysed by sucrase
11
Q
What is roughage?
A
- Non hydrolysable polysaccharides in the diet
- Plant polysaccharides
- Can be degraded by some extent by bacterial enzymes
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
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
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
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
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
What is the anti-oxidant function of glutathione?
- 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
Describe G6PDH deficiency
- 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
Describe metabolism of fructose
- 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
Describe metabolism of galactose
-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
Describe alcohol metabolism
- 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
Describe metabolism of toxic alcohols
- 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
