Energy Production - Carbs 1,2,3 Flashcards
What is metabolism?
The inter conversion of biological molecules in small chemical steps
Name + define the two types of metabolic pathways
Catabolic - oxidative (release H) + the breakdown of large molecules into smaller intermediates + releases large amounts of energy
Anabolic - reductive + the synthesis of larger molecules from smaller intermediates + uses the energy released from catabolism
What types of energy carriers are released in catabolism?
- reducing power - NADH, NADPH, FADH2
- energy - ATP
How is reducing power converted to ATP?
Oxidative phosphorylation
What is the purpose of stage 1 in catabolism?
To convert nutrients from a form that can be taken up into cells
e.g. carbs > monosaccharides
Lipids > glycerol + fatty acids
Proteins > amino acids
Where does stage 1 catabolism occur?
Extracellularly (GI tract)
Does stage 1 catabolism produce energy?
No
What is the purpose of stage 2 catabolism?
Degradation of building blocks to small number of organic precursors
Glycolysis occurs here»_space; ATP made
Where does stage 2 catabolism occur?
Intracellularly - cytosolic + mitochondrial
Does stage 2 catabolism produce energy?
Glycolysis occurs here so yes
Some ATP
What occurs in stage 3 catabolism?
Tricarboxylic acid cycle - Kerb’s cycle
Does stage 3 catabolism produce energy?
GTP produced
What occurs in catabolism stage 4?
Oxidative phosphorylation - ETC + ATP synthesis
What is required for stage 4 catabolism?
Oxygen to act as the final electron acceptor
Does stage 4 catabolism produce energy?
Lots of ATP - oxidative phosphorylation
What is the general formula for carbs?
(CH2O)n
What are the stages of catabolism?
Stage 1 - breakdown to monomers
**Stage 2* - breakdown to metabolic intermediates - glycolysis
Stage 3 - tricarboxylic acid cycle
Stage 4 - oxidative phosphorylation
How many units are oligosacharides?
3-12
What is sucrose made up of?
Glucose-fructose
What is lactose made up of?
Galactose-glucose
What is maltose made up of?
Glucose-glucose
What is the glucose concentration in blood?
5mM
What cells have an absolute requirement for oxygen and why?
Red blood cells - no mitochondria
Lens of eye - no mitochondria
Neutrophils - low O2 environment
Innermost cells of kidney medulla - low O2 environment
What enzymes are in your saliva for metabolism of carbs?
Amylase
What enzymes are in the pancreas for metabolism of carbs?
Amylase
What enzymes are in your small intestine for carb metabolism?
Lactase
Sucrose
Pancreatic amylase - a 1-4 bonds
Isomaltase - a 1-6 bonds
What is primary lactase deficiency?
Absence of lactase persistence allele - mainly in northwest Europe
Only occurs in adults
What is secondary lactase deficiency?
Caused by injury to small intestine:
- gastroenteritis
- coeliac disease
- Crohn’s disease
- ulcerative colitis
In both infants + adults
What is Congential lactase deficiency?
Autosomal recessive defect in lactase gene
Cannot digest breast milk
Symptoms of lactose intolerance
Bloatin/cramps
Flatulence - accumulation of gas
Diarrhoea
Vomiting
Rumbling stomach
How are monosaccharides absorbed?
1- active transport into intestinal epithelial cells by sodium dependent glucose transporter 1 SGLT1
2- passive transport via GLUT2 into blood
3- transported in blood to target cells
4- glucose uptake via facilitated diffusion using GLUT1-5
Na+/K+ ATPase needed to maintain conc. gradient for SGLT1
What role does Na+/K+ ATPase have in the absorption of monosaccharides?
Maintains the conc gradient for the SGLT1
Where is GLUT1 present?
All cells
Where is GLUT 2 present?
Main abdominal organs:
- kidney
- liver
- pancreatic B cells
- small intestine
Where is GLUT3 found?
Neurones
Placenta
Where is GLUT4 found?
Adipose tissue
Striated muscle
What regulates GLUT4?
Insulin
Where is GLUT 5 found?
Spermatozoa
Large intestine
What GLUT is in abdominal organs?
GLUT2
Functions of glycolysis
Oxidation of glucose
NADH production
ATP synthesis
Provides biosynthesis precursors for fatty acids
Features of glycolysis
Central pathway of CHO catabolism
Occurs in all tissues - cytosolic
Exergonic - produces energy
Oxidative
Irreversible
What are the key enzymes in glycolysis?
- hexokinase (glucokinase in liver)
- phosphofructokianse-1
- pyrivate kinase
What is phosphofructokinase-1 regulated by?
allosteric
1- inhibited by high ATP + citrate
2- stimulated by high AMP + F2,6,BP
hormonal
1- inhibited by glucagon
2- stimulated by insulin
Why are there so many steps in glycosides?
- Easier in smaller steps
- Efficient energy conservation
- Gives versatility - intermediates can be used in other pathways
- Fine control - easier to slowdown/speed up specific parts
What is allosteric binding?
Binding at another site
Why is phosphofructokinase reaction irreversible?
Very negative delta G
What is the most important enzyme in glycolysis regulation?
Phosphofructokinase
What activates pyruvate kinase?
High insulin:glucagon ratio
(High insulin, low glucagon)
How is NAD+ regenerated?
Oxidative phosphorylation
Lactate dehydrogenase
What is lactate dehydrogenase important for?
Regenerating NAD+ when oxygen is low
What is plasma lactate concentration determined by?
Relative rates of:
- production
- utilisation - liver, heart, muscle
- disposal - kidney
What is the normal concentration of plasma lactate?
<1mM
What is the plasma lactate concentration in hyperlactaemia?
2-5mM
Below renal threshold
No change in blood pH
What is the plasma lactate concentration in lactic acidosis?
> 5mM
Above renal threshold
Blood pH lowered
Where is fructose metabolism?
Liver
Outline fructose metabolism
fructokinase aldolase
Fructose > fructose-1P >glyceralaldehyde-3-P
Diseases related to fructose metabolism
Essential fructosuria - fructokinase missing
Fructose intolerance - aldolase missing
What is essential fructosuira?
Fructokinase missing
Fructose in urine
What is fructose intolerance?
Aldolase missing
Fructose-1P accumulates in liver»_space; liver damage
Managed by removing fructose + sucrose in diet
A deficiency in fructokinase causes what?
Essential fructosuria
How is essential fructosuria detected?
No clinical signs
Fructose in urine
What does a deficiency in aldolase cause?
Fructose intolerance
Management of fructose intolerance
Remove fructose + sucrose from diet
Deficiencies in what enzymes cause galactosaemia?
Galactokinase
Uridyl transferase
UDP-galactose epimerise
What is galactosaemia?
Inability to utilise galactose
What is the most common cause of galactosaemia?
Galactose-1P uridyl transferase deficiency
Galactose + galactose1-P accumulate
Complications of galactosaemia
Galactose enters other pathways
aldose reductase
Galactose > galactitol
Accumulation of galactose + galactitol cause swelling + protein precipitation
Increased aldose reductase activity uses excess NADPH
- Crystallin protein denatures»_space; Cataract
What does build up of galactose 1P cause?
Damage to liver, kidney + brain
What do Heinz Bodies suggest?
G6PDH deficiency
What molecule plays an important role in regulating the affinity of haemoglobin for O2?
2,3-bisphosphoglycerate
What are Heinz bodies caused by?
Precipitated haemoglobin aggregates + binds to cell membrane
What are Heinz bodies removed by?
Spleen
What can a deficiency in pyruvate dehydrogenase cause?
Lactic acidosis
- Pyruvate cant be converted to acetyl CoA
- anaerobic respiration occurs to regenerate NAD+
- lactate build up
What is pyruvate dehydrogenase sensitive to and why?
Vitamin B1
Requires coenzymes which are provided by vit B
What is pyruvate dehydrogenase activated by?
Pyruvate
NAD+
ADP
Insulin
What is pyruvate dehydrogenase inhibited by?
Acetyl CoA
NADH
ATP
Citrate
Outline the intermediates in the TCA cycle?
Citrate
Isocitrate
a-ketogluarate
Syccinyl-coA
Succiante
Fumarate
Maleate
Oxaloacetate
Net gain from TCA cycle
6 NADH
2FADH2
2GTP
How is the TCA cycle regulated?
Energy availability
Isocitrate dehydrogenase - rate limiting enzyme
a-ketoglutarate dehydrogenase
Key features of oxidative phosphorylation
- ETC + ATP synthesis
- NADH + FADH2 reoxidation
- lots of ATP produced
- O2 acts as final electron acceptors
Outline oxidative phosphorylation
1- NADH + FADH2 get reoxidised
2- energy from this powers proton translocating complexes
3- H+ ions move from matrix to intermembrane space which creates a proton motive force
4- H+ attach to ATP synthase
5- ADP»_space; ATP
How does high ATP conc regulate oxidative phosphorylation?
Low [ADP] - no substrate for ATP synthase
Inwards H+ flow stops
Increase in H+ in inter membrane space
ETC + ATP synthesis stops
Two processes of using reducing power in ATP synthesis
1- electron transport - e- from NADH + FADH2 transferred through ETC
2- oxidative phosphorylation - free energy released used to drive ATP synthesis
How many molecules of ATP is produced from 1 NADH?
2.5ATP
How many molecules of ATP are produced from 1FADH2?
1.5
What proof translocatioing complexes does NADH + FADH2 use?
NADH - Complexes I, III, IV
FADH2 - complexes III + IV
What effect to inhibitors have on oxidative phosphorylation?
Block ETC by blocking O2 acting as FEA
Examples of inhibitors
Cyanide
Carbon monoxide
What effect do uncouplers have on oxidative phosphorylation?
- Increases membrane permeability to H+
- stops PMF
- H+ cross membrane without passing through ATP synthase so no ATP synthesis
- no inhibition of ETC
Examples of uncouplers
Fatty acids
Dinitrocresol
Dinitrophenol
Compare oxidative phosphorylation + substrate level phosphorylation (4 points)
Oxidative phosphorylation
- requires membrane-associated complexes
- cannot occur without O2
- major process for ATP synthesis
- energy cooling occurs indirectly through generating + using PMF
Substrate level phosphorylation
- requires soluble enzymes
- can occur to an extent without O2
- minor process for ATP synthesis
- energy coupling occurs directly through formation of high energy of hydrolysis bond
How does energy coupling occur in oxidative phosphorylation?
Indirectly through generating and using PMF
How does energy coupling occur in substrate level phosphorylation?
Directly through formation of high energy of hydrolysis bond
Symptoms of galactosaemia
Cataracts
Hypoglycaemia
Hepatomegaly + cirrhosis
Renal failure
Vomiting
Seizure + brain damage
Function of the outer and inner membrane of mitochondria
Allows a proton gradient to be formed