Lecture 2 - Carbohydrates Flashcards
What are the 4 different stages of catabolism?
- Breakdown of nutrients to forms that can be absorbed by cells (a.a/monosaccharides/f.a)
[no energy released] - Degradation of block molecules to organic precursors
[energy released] - Krebs cycle
- Oxidative Phosphorylation
What is the general structure of carbohydrates?
- General formula (CH2O)n
- Contain aldehyde or keto- group
- Split into mono-/di-/oligo-/poly-
What are cells that have absolute requirement for glucose?
- RBC
- WBC
- Cells of kidney medulla
- Lens of the eye
N.B Brain & CNS prefer glucose but can metabolise ketone bodies in starvation state
Where does stage 1 of catabolism, the breakdown of nutrients occur?
GI tract
Describe the stages of carbohydrate digestion in the body (location, enzymes)
- Saliva = Amylase (starch –> glycogen)
- Pancreas - Amylase
- Small intestine = Lactase, Sucrase, Isomaltase, Amylase
Why can’t cellulose be digested?
No enzyme in body to break down β-1,4 link
What are some primary and secondary causes of lactase deficiency?
Primary:
- Absence of lactase persistence allele
- Adults
Secondary:
- Caused by injury to small intestine (Crohn’s disease, Coeliac disease)
- Adults and infants
- Reversible
Congenital lactase deficiency {extremely rare}
- Autosomal recessive defect in lactase gene
What are some symptoms of lactase deficiency?
- Bloating/cramps
- Flatulence
- Diarrhoea
- Vomitting
Why does diarrhoea and bloating occur in lactase deficient patients?
Bacteria in gut digests lactose –> lactase –> osmotic effect –> draws water into gut –> diarrhoea AND produce H2, CO2 –> bloating
How are sugars absorbed by the body?
- Active transport
- Passive transport (GLUT 2)
- Facilitated diffusion by target cells
What does stage 2 of metabolism involve?
Where does it occur?
- Breakdown of metabolic intermediates
- Glycolysis –> NADH, ATP
- Occur in cytoplasm
What is the function of glycolysis?
*occurs in all tissues (cytosolic)
- Oxidation of glucose: produce C6 and C3 intermediates
- Produce: x2 NADH, X2ATP, X2 Pyruvate (C3, END)
[per mole of glucose]
What are some features of glycolysis?
- Central pathway of C metabolism
- Occurs in all tissues (cytosolic)
- Exergonic (irreversible)
- C6 –> X2 C3
- Enzyme LDH only way to do it anaerobically
What are the enzymes involved in glycolysis? What reactions do they catalyse? x3
- Glucose –> Glucose-6-phosphate
[Hexokinase/Glucokinase (liver)]
[1 mole of ATP used] - Fructose-6-P –> Fructose 1,6- bis-P
[Phosphofructokinase]
[1 mole of ATP used] - Phosphoenolpyruvate –> Pyruvate
[Pyruvate kinase]
[1 mole ATP released]
N.B: ALL STEPS ARE IRREVERSIBLE
Why are so many enzymes involved in glycolysis?
- Efficient energy conservation
- Allows for fine control
- Useful intermediates formed
- Allows for reverse reactions
Why does the phosphorylation of glucose to glucose-6-P occur?
- Makes glucose negatively-charged: prevent travel across membrane
- Increase reactivity of glucose
- Uses 2 mole of ATP
- Large G value, irreversible
Which reaction is committing step of glycolysis?
Fructose-6-P –> Fructose -1,6- bis-P
[Phosphofructokinase]
Which 2 steps produce ATP in glycolysis? What type of phosphorylation is this?
- 1,3-bis-phosphoglycerate –> 3-phosphoglycerate
- Phosphoenolpyruvate –> Pyruvate
[Pyruvate Kinase] - Sub- level P
1,3-bisphosphoglycerate is catalysed into a by b. What is the function of a?
a = 2,3-Bisphosphoglycerate (2,3-BPG) b = Bisphosphoglycerate mutase - Function of 2,3-BPG: i) Produced in RBC ii) Reduce affinity of Hb to O2 (shift right)
Glyceraldehyde 3-P is converted to a then b by c. What is the function of b?
a = Dihydroxyacetone-P (DHAP) b = Glycerol phosphate c = Glycerol 3-P dehydrogenase - Function of b: TAG and phospholipid synthesis [produced in liver & adipose]
What is the clinical application of glycolysis?
- Rate of glycolysis higher in cancer
- Measure uptake of radioactive modified hexokinase sub. (FDG)
- Imaging with positron emission tomography (PET)
Step 6 of glycolysis (glyceraldehyde 3-P–> 1,3 BPG) is stopped when NADH increases why?
- Ratio of NAD+/NADH is constant –> all glycolysis would stop when all NAD+ converted
RBC has no mitochondria but needs to regenerate NAD+ somehow. Suggest a route
- LDH reaction
(NADH + H+ + Pyruvate —> NAD+ + lactate) - Catalysed by LDH
How is plasma concentration of lactate controlled?
- Conc. determined by rate of production/utilisation/disposal
- Normally kept constant < 1mM
When is lactate produced?
- W/o major exercise (RBC, skin, brain)
- Exercise
- Pathological situations (shock)
What ranges are hyperlactatemia and lactic acidosis?
- Hyper:
i) 2-5mM
ii) Below renal threshold
iii) No change in blood pH (buffering capacity) - L.A:
i) Above 5mM
ii) Above renal threshold
iii) pH ⬇️
Phosphofructokinase, PFK is a key regulator of glycolysis. What are some allosteric/hormonal regulations that controls it?
Allosteric:
- Inhibited by high energy signals (NADH, ATP)
- Stimulated by low energy signals (AMP, ADP)
Hormonal:
- Stimulated by insulin
- Inhibited by glucagon
How does glucose-6-P inhibit enzyme hexokinase?
- By allosteric regulation
- Inhibition in further steps of glycolysis (3 & 6) by high energy signals prevents metabolism of F-6-P —> G-6-P ⬆️–> X hexokinase
What reaction does aldolase catalyse? And what occurs when aldolase is missing and fructokinase is missing?
- Fructose-1-P –> glyceraldehyde + DHAP
- Fructokinase X = Fructose in urine (fructosuria)
- Aldolase X = Fructose 1-P ⬆️–> liver damage
[ Treatment: remove fructose from diet]
Describe the enzymes and reactions in galactose metabolism
- Galactose –> Galactose-1-P
[Galactokinase] - Galactose-1-P –> Glucose-1-P
[G-1-P uridyl transferase] - UDP-Galactose –> Galactose-1-P
[UDP-G epimerase]
What does galactokinase deficiency result in and how often is it? Vice versa for transferase. Suggest a treatment.
- Galactokinase X = galactose ⬆️
[rare] - G-1-P transferase X = Galactose-1-P AND galactose ⬆️
- No galactose in diet
What happens when galactose accumulates?
- Enters different pathway
- Galactose –> Galactitol
[Aldose Reductase] - Deplete NADPH –> Causes random formation of disulphide bonds –> loss of structural integrity –> lens of eye become cloudy
What is the importance of PPP?
- Generate NADPH –> recycle glutathione to reduced form –> protects against oxidative dmg –> no random disulphide bonds form
- Form C5 sugar: synthesis of DNA & RNA
Where does PPP occur and which enzyme catalyses the reaction?
- Occurs in cytosol
- Enzyme: Glucose-6-dehydrogenase
[Reaction: G-6-P –> 5C sugars +NADPH+CO2]
What are some features of PPP?
enzyme, regulation, products
[Reaction: G-6-P –> 5C sugars +NADPH+CO2]
- Loss of CO2 = irreversible
- No ATP produced
- Controlled by NADP+/NADPH ratio
- Rate-limiting enzyme = G6PDH
Importance of PPP in RBC is? What happens if PPP x occurs?
- Only source of NADPH –> no mitochondria
- If ❌PPP –> NADPH ⬇️ –> disulphide bond forms –> aggregate proteins, Heinz bodies –> haemolytic anaemia
