Session 2 ILO's - Energy Production (Carbohydrates 1 and 2) Flashcards

1
Q

Describe the general structure of carbohydrates (4)

A
  • General formula (CH2O)n (i.e. hydrated carbons)
  • May contain aldehyde -CHO (aldose) or keto (-C=O) (ketose) groups
  • Contain multiple OH groups
  • Can be:

Monosaccharides (single sugar unit, 3-9 carbons, ie triode sugar = 3, pentose sugar = 5, hexose sugar =6)

Disaccharides (2 sugar units)

Oligosaccharides (3-12 sugars, ie dextrins) or

Polysaccharides (10-1000’s of units)

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2
Q

Describe briefly how carbohydrates are digested and absorbed.

DIGESTION

A
  • Breakdown occurs extracellularly in the GI tract in stage 1 of carbohydrate metabolism
  • Large molecules get broken down into building blocks/monosaccharide molecules by:

1) Salivary amylase (starch and glycogen get broken down into smaller dextrin, oligosaccharide molecules)

2) Pancreatic amylase continues to work on the dextrins to break them down into monosaccharides.

3) In the intestine, we have a number of disaccharidases - enzymes that are specifically looking for disaccharides to complete the digestion into monosaccharides:

  • lactase(cleaves lactose)
  • sucrase(cleaves sucrose)
  • Pancreatic amylase(Finishes off the glucose a1-4 bonds, the linear chain bonds)
  • isomaltase(cleaves the a1-6 bonds, the branching bonds)
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3
Q

Describe briefly how carbohydrates are digested and absorbed.

ABSORBTION

A
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4
Q

Briefly describe by which processes sugars are absorbed

A
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5
Q

Which 2 Glucose transporters do you need to know, and where are they found?

A

GLUT2 - Kidney, Liver, Pancreatic beta cells, small intestine

GLUT4 - Adipose tissue, Striated muscle (target tissues for insulin/) GLUT 4 is insulin regulated

(Just be aware that there are a number of glucose transporters)

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6
Q

Name and describe the functions of the main 7 dietary carbohydrates

A
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7
Q

Describe the general functions of carbohydrates.

A
  • Mainly supply energy
  • Dietary carbs have many different functions (see on later flashcard)
  • Glucose is a carb some tissues have an absolute requirement for (see on later flashcard)
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8
Q

Describe the glucose dependancy of some tissues

Which cells have an absolute requirement for glucose?

A
  • Red blood cells
  • Neutrophils
  • Innermost cells of kidney medulla
  • Lens of the eye

This is because these cells are unable to carry out glycolysis and cannot perform stage 3 or 4 of metabolism (they can only metabolise glucose)

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9
Q

Describe the glucose dependancy of some tissues

Describe the brain’s usage of glucose

A

The CNS (brain) prefers glucose as fuel, but can use ketone bodies for some energy requirements in times of starvation, but needs time to adapt)

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10
Q

Explain why cellulose is not digested in the human gastrointestinal tract.

A
  • Between it’s glucose units, cellulose has beta 1,4 glycosidic bonds
  • The human body does not have the enzymes required to break down the beta 1,4 glycoside bonds present in dietary fibres, ie no cellulase
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11
Q

Explain the biochemical basis of the clinical condition of lactose intolerance.

A
  • Failure to digest lactose due to lactase deficiency
  • Thus, if lactose is ingested, it will persist in the colon, where bacteria would break it down
  • The presence of lactose in the lumen of the colon increases the osmotic pressure of the contents and will draw water into the lumen, causing diahhorea.

(AKA lactose remains as an osmolite and it attracts water in the GI tract and can lead to the symptoms of lactose intolerance e.g. cramping, diarrhoea etc)

  • Colonic bacteria can produce hydrogen, carbon dioxide and methane gas from lactose, causing feelings off bloating and discomfort.
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12
Q

What are the 3 types of lactose intolerance?

A
  • Primary lactase deficiency
  • Secondary lactase deficiency
  • Congenital lactase deficiency
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13
Q

Describe Primary lactase deficiency

A
  • Absence of lactase persistence allele.
  • Highest prevalence in Northwest Europe * Only occurs in adults
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14
Q

Describe Secondary lactase deficiency

A

1) Caused by injury to small intestine:
* Gastroenteritis
* Coeliac disease
* Crohn’s disease
* Ulcerative colitis

2) Occurs in both infants & adults

3)Generally reversible

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15
Q

Describe Congenital lactase deficiency

A
  • Extremely rare, autosomal recessive defect in lactase gene.
  • Cannot digest breast milk.
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16
Q

Which 2 monosaccharides make up lactose?

A
  • Glucose and Galactose
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17
Q

Give 6 Symptoms of Lactose intolerance

A
  • Bloating/cramps
  • Flatulence (Farting)
  • Diarrhoea
  • Vomiting
  • Rumbling stomach
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18
Q

Name 5 foods that contain lactose

A
  • Milk
  • Cream
  • Yoghurt
  • Cheese
  • Many processed
    foods
19
Q

Describe the clinical condition of glucose 6-phosphate dehydrogenase deficiency and explain the biochemical basis of the signs and symptoms.

A
  • Very common inherited defect where the enzyme that converts glucose-6-phosphate into pentose sugar phosphates is deficient.
  • Therefore less NADPH is produced, so we aren’t able to prevent the formation of inappropriate disulphide bonds.
  • If inappropriate disulphide bonds form, proteins aggregate and form heinz bodies and this leads to haemolysis = anaemia!
  • Also, less NADPH means inappropriate disulphide bonds form so proteins in the lens of the eye get depleted.
  • This structure damage leads to cataracts.

Symptoms:
- Jaundice due to haemolysis (as there is a build up of bilirubin)
- Cataracts

20
Q

Describe the key features of glycolysis (10)

A
  • Central pathway of carbohydrate metabolism
  • Occurs in all tissues (cytosolic)
  • The process is exergonic (with a negative delta G value) and oxidative
  • The starting material, end-products and intermediates are C6 or C3
  • There is no loss of CO2
  • Glucose (6 Carbon sugar) is oxidised to pyruvate (x2 3carbon sugars)
  • NAD+ is reduced to NADH (2 NADH produced per glucose)
  • With one additional enzyme, (PDH), it is the only pathway that can operate anaerobically
  • Irreversible pathway
  • 2 moles of ATP are required to activate the process and 4 moles of ATP are produced by the process, giving a net yield of 2 moles of ATP
21
Q

Give 4 functions of glycolysis

A
  • Oxidation of glucose
  • NADH production (2 per glucose)
  • Synthesis of ATP from ADP (net= 2 ATP per glucose)
  • Produces C6 and C3 intermediates for other uses
22
Q

Name the 3 important enzymes involved in glycolysis

A
  • Hexokinase (Enzyme 1)
  • Phosphofructokinase-1 (the most important enzyme in the regulation of glycolysis (Enzyme 3)
  • Pyruvate Kinase (Enzyme 10)
23
Q

Describe how key metabolites may be derived from glycolysis

A

In the pathway:

  • 1,3-biphosphoglycerate may be converted to 2,3-biphosphoglycerate by bisphosphoglycerate mutate which is important in oxygen transport
  • DHAP can be converted to glycerol phosphate by glycerol-3-phosphase dehydrogenase which is important in lipid synthesis, triglyceride&phospholipid biosynthesis etc.
24
Q

Explain how sugars other than glucose are metabolised

A
  • Fructose is converted to fructose-1-p by fructokinase (investment of ATP) and aldolase converts this into glyceraldehyde and triose kinase converts this to glyceraldehyde-3-p which then feeds into glycolysis
  • Galactose is converted to galactose-1-p by galactokinase and can be converted into glucose-1-p by uridyl transferase and then glucose-6-p to be entered into glycolysis. However, galactose-1-p can also be converted into UDP galactose by UDP-galactose-epimerase which can be converted to UDP-glucose and then glycogen
25
Q

Explain the key role of lactate dehydrogenase in glucose metabolism

A

In poor O2 tissues, lactate dehydrogenate can metabolise pyruvate and NADH to produce NAD+ required for glycolysis of glucose
It can also work to remove lactate in well oxygenate tissues by converting lactate and NAD+ into pyruvate and NADH

26
Q

Explain why lactic acid (lactate) production is important in anaerobic glycolysis.

A
  • Pathway needs a continuous supply of NAD+ and normally NAD+ is regenerate in stage 4 of metabolism. However, in cells that don’t have stage 3/4, then lactate dehydrogenase can regenerate NAD+ along with lactate (from metabolising pyruvate)

The lactate can then be metabolised in the liver and kidney or heart back into pyruvate for energy (or gluconeogenesis in the liver only)

27
Q

Explain the biochemical basis of the clinical conditions of
galactosaemia

A
  • A deficiency in the following enzymes can because galactosaemia: galactokinase, uridyl transferase or UDP-galactose epimerase.
  • A deficiency in any enzyme saturates the other 2 enzymes and causes greater formation of galactose (less breakdown of galactose) and therefore galactose is converted to galactitol by aldose reductase (NADPH->NADP+) which can increase osmotic pressure as well as depleting NADPH which protects against oxidative damage
  • Depleting NADPH affects protein structure = cataracts and anaemia due to haemolysis
28
Q

Explain why the pentose phosphate pathway is an important metabolic pathway in some tissues.

A

2 main reasons:

  1. Process uses NADP+ instead of NAD+, NADPH produced is important in providing reducing equivalents in biosynthesis (also protects again oxidative damage & maintain S-H bonds in proteins)
  2. Pentose sugar phosphates are important in providing sugar in the production of nucleotides and ATP (DNA, RNA, coenzymes)
29
Q

Describe the key features of the control of glycolysis

Describe the regulation of phosphofructokinase-1 and pyruvate kinase

A

COME BACK TO THIS

Phosphofructokinase-1 (the enzyme that catylyses step 3) is the key regulatory enzyme

Subject to regulation by:
1. Allosteric regulaltion (muscle):
- Phosphofructokinase-1 has an allosteric site for both ATP and AMP

  • Phosphofructokinase-1is inhibited (turned down) by high ATP and citrate and stimulated by high AMP and high F2,6 and BP (low energy signal) (so high ATP tells the cell that we don’t need more catabolism going on and high AMP tells the cell that we need more catabolism going on)
  1. Hormonal regulation (liver):
    Phosphofructokinase-1 is stimulated by insulin and inhibited by glucagon
    Pyruvate kinase (enzyme 10) is also regulated in the same way!!
30
Q

Describe the key features of the control of glycolysis

Describe the regulation of hexokinse

A

Hexokinase (enzyme 1) can also be regulated by allosteric inhibition by glucose-6-phosphate

31
Q

Describe the metabolic regulation of glycolysis

A
32
Q

What is allosteric regulation?

A

Modulating protein activity by the binding of an effector ligand at a site that is not the active site. Can inhibit or activate.

33
Q

CARDS AFTER THESE ARE EXTRAS, NOT PART OF ILO’S BUT FOR UNDRSTANDING

A
34
Q

How many sugar units are found in:
a) Monosaccharides
b) Disaccharides
c) Oligosaccharides
d) Polysaccharides

A
35
Q

Describe the different principals of the regulation of metabolic pathways

A

1.a. Allosteric regulation (ratio of ATP:ADP, NAD+/NADH etc)
1.b. Phosphorylation/dephosphorylation - hormone receptor binding activates either protein kinases or phosphotases
2. Product inhibition (last product inhibits first step)
3. Committing step (if inhibited, product can be diverted into other pathways)

36
Q

Explain the key role of pyruvate dehydrogenase in glucose metabolism - what factors activate the enzyme and which factors inactivate the enzyme?

A

Pyruvate dehydrogenase converts pyruvate into acetyl CoA and releasing CO2 in an IRREVERSIBLE / UNIDIRECTIONAL reaction (pyruvate can’t enter directly into the cycle)
If Pyruvate dehydrogenase was deficient, pyruvate couldn’t enter the Krebs cycle and it would build up and be diverted out to lactate dehydrogenase
Activated by: pyruvate, NAD+, ADP, insulin
Inhibited by: acetyl-CoA, NADH, ATP, citrate

37
Q

Describe the roles of the Krebs cycle in metabolism (overview)

A

Acetyl CoA is oxidised to produce 2 x CO2 and some energy produced by substrate level phosphorylation

Also produces precursors for biosynthesis:
Per cycle (x 2 for per glucose):
3 x NADH
1 x FADH2
1 x GTP
These can then be used to drive the electron transport chain to produce much more ATP

38
Q

Explain how the TCA cycle is regulated

A

Regulation occurs at 2 enzymes
1. Isocitrate dehydrogenase
2. Alpha-ketoglutarate dehydrogenase
Both enzymes activated by low energy compounds e.g. AMP, NAD+
Both enzymes inhibited by high energy compounds e.g. ATP, NADH

39
Q

Describe the key features of oxidative phosphorylation

A

Occurs in the mitochondria
NADH & FADH2 are re-oxidised
O2 is required (reduced to H2O - gains oxygen)
Lots of ATP is produced

40
Q

Explain the processes of electron transport and ATP synthesis and how they are coupled

A

Electrons are transferred through a series of carrier molecules along to O2, with release of energy
30% of energy is used to move H+ across the membrane, whilst 70% is released as heat (maintain core body temp)
Movement of the H+ across the membrane, creates a proton motive force and this drives the movement of H+ back across through the ATP synthase - which drives the conversion of ADP to ATP = energy production!!! :)

41
Q

Describe how, when and why uncoupling of these processes occurs in some tissues

A

Uncoupling increase the permeability of mitochondrial inner membrane to protons, which dissipates the proton motive force and hence there is less of a driving force for ATP synthesis
Uncoupling occurs in brown adipose tissue (which contains UCP1) because it allows for extra heat generation and maintains heat in newborn infants
Noradrenaline is released in response to cold, which actives lipases to release fatty acids which active UCP1 = heat generation

42
Q

Compare the processes of oxidative phosphorylation and substrate level phosphorylation

A

Substrate level phosphorylation (SLP) requires soluble enzymes, whereas Oxidative Phosphorylation (OP) requires membrane associated complexes
SLP occurs directly through formation of high energy bonds, whereas OP uses p.m.f to indirectly generate energy coupling
SLP can occur to an extent anaerobically, whereas OP cannot occur anaerobically
SLP minorly contributes to ATP synthesis in cells requiring large amounts of energy, whereas OP is the major ATP generator!

43
Q

Make sure to add on self assessment answers

A
44
Q

Describe the beginning of digestion

A

Broken down - GI Tract
Absorbed - Small intestine

  • Carbohydrates are broken down into building blocks, extracellularly in the GI tract by ‘glycosidase enzymes’
  • This process of digestion starts almost straight away
  • Salivary amylase starts to cleave starch and glycogen into smaller oligosaccharides like dextrins
  • Once the chyme reaches the stomach, digestion by amylase is temporarily halted, because the acidic environment inactivates the enzyme amylase
  • In the pancreas, pancreatic amylase breaks the dextrins down further into monosaccarides
  • In the small intestine, disc