Topic 6: Energy production - Carbohydrates Flashcards
What type of molecules does catabolism break down
amino acids, glucose, fatty acids, alcohol
what intermediate metabolite is formed
acetyl coA
what is acetyl coA further metabolised into
CO2
what are the 4 stages of catabolism
- breakdown of fuel to building blocks for absorption (GI tract). breakage of C-N AND C-O bond, no energy released
- breakdown into intermediates through many pathways (cytosol or mitochondria). this is oxidative (some energy released), C-C bond broken
- krebs cycle in mitochondria. this is oxidative, acetyl coA to C02
- electron transport chain and oxidative phosphorylation, reducing power into ATP
what does oxidative mean
release of reducing power + energy
describe stage 1 of catabolism
- extracellular (GI tract)
- so nutrients are converted into a form that can be taken up by cells (carbs etc too big -> monosaccharides, amino acids etc)
- forms building block molecules which absorbed from GI tract
- no energy released
describe stage 2 of catabolism
- intracellular (cytosolic or mitchondrial)
- many pathways
- building blocks into simpler molecules. many to few molecules
- oxidative so requires coenzymes like NAD+ -> NADH
- some energy released
describe stage 3 of catabolism
- in mitochondria
- cyclic, single pathway - KREBS CYCLE
- oxidative pathway (requires NAD+ and FAD)
- some energy produced as GTP
- acetyl to 2CO2
- produces precursors
describe stage 4 of catabolism
- in mitochondria
- electron transport chain and ATP formed
- NADH and FADH2 re-oxidised
- O2 required
- lots of ATP produced
how much carbs in an adult
1% in comparison of 15% intake
what are the 3 main dietary monosaccharides
glucose
fructose
galactose
what is the concentration of glucose in the blood
5mM
which cells have an absolute requirement for glucose
red blood cells
neutrophils
innermost cells of kidney medulla
lens of the eye
what does CNS use as fuel
glucose
can use ketone bodies if required
how are dietary carbohydrates broken down in stage 1 of catabolsim
saliva - amylase breaks down starch and glycogen -> dextrins
pancrease - amylase breaks down monosacchardies
small intestine - disccharidases break down disaccharides -> monosaccharides
what are the different disaccharidases
lactose
sucrase
pancreatic amylase (alpha 1-4)
isomaltase (alpha 1-6)
why can’t the body break down cellulose
no enzymes to break down beta 1-4 linkages
can not hydrolyse as beta glycosidic bonds are different
how does lactose intolerance occur
Primary lactose deficiency-
absence of lactase persistence allele as mature, can not produce lactase as adults
secondary -
caused by injury to small intestine (gastroenteritis, coeliac disease, crohn’s, ulcerative colitis\0
in infants and adults, can be reversible
congenital -
autosomal recessive defect in lactase gene, cannot digest breast milk
how are monosacharide absorbed into the GI tract in stage 1 of catabolism
- active transport into intestinal epithelial cells by sodium dependent glucose transport 1 (SGLT1)
- passive transport via GLUT2 into bloody supply
- travels in blood to tissues
- glucose taken up in target cells via faciliated diffusion using transport proteins (GLUT1-GLUT5)
what are the different glucose transporters and where are they found (not really need)
GLUT1 - fetal tissues, adult erythroctyes, blood-brain barrier
GLUT2** - kidney, liver, pancreatic beta cells (insulin dependent), small intestine
GLUT3 - neurons, placenta
GLUT4** - adipose tissue, striated muscle
GLUT5 - spermatazoa, intestine
what is the main feature of stage 2 of catabolism
glycolysis
what are the functions of glycolysis in stage 2
aim to breakdown glucose into 2 x3C pyruvate
oxidation of glucose so NAD+ reduced
NADH production (2 for every glucose)
synthesis of ATP (2ATP per glucose, 4 results but 2 used to activate)
what are the features of glycolysis in stage 2
in all tissues which is cytosolic exergonic, oxidative - releases energy with oxidation of substrates no loss of CO2 lactate dehydrogenase is also formed irreversible
what enzymes are involved in glycolysis in stage 2
Hekokinase (glucosekinase in liver)
Phosphofructokinase-1
Pyruvate kinase
why are there so many steps and enzymes in glycolysis
effienct energy conservation
gives versatility because allows interconnections with other pathways to produce other metabolic intermediates
allows fine control
allows part to be used in reverse
what is phase 1 of glycolysis
- glucose enters the cell
phosphorylated by ATP and forms ADP to form glucose-6-phosphate. the phosphate group is negatively charged so prevents backflow into membrane into blood flow - an isomeration step to form fructose - 6 - phosphate
- ATP used to phosphorylation to form fructose 1, 6- bis phosphate
how much energy is formed during glycolysis
2ATP per glucose
reaction 1 and 2 of phase 1 has large delta G reaction so irreversible
after step 3 the substrate must move on to the rest of glycolysis
what is phase 2 of glycolysis
- fructose 1,6 bisphosphate is cleaved into 2 x 3C units(isomerised first to DHAP and forms two glyceraldehyde 3-phosphate)
- NAD+ is reduced to oxidise glyceraldehyde 3-phopshate to 1,3 bis phosphoglycerate (a phosphate is also added)
- large negative delta G of hydrolysis, so irreversible. substrate level phosphorylation occurs to form ATP and 3-phosphoglycerate
- further isomeration to form 2-phosphoglycerate and then phosphoenolypyruvate
- large negative delta G of hydrolysis, so irreversible. ATP formed and converts to pyruvate
how do you make glucose from pyruvate
using reversible reactions
gluconeogenesis
what does glycolysis porduce
2 moles of ATP
what happens when rate of glycolysis increases
up to 200 times faster in cancer
measured using radioactive marker and PET
what other intermediates can be formed from glycolysis
- fat is formed at cleavage
from DHAP instead of forming glyceraldehyde 3 phosphate. the enzyme, glycerol 3 -phophate dehydrogenase which reduces it (accompanied by the oxidation of NAD) forms glycerol phosphate
which can then synthesis triglyceride and phospholipid biosynthesis
glycerol phosphate + fatty acids -> fat - 2,3 - bisphosphoglycerate produced from 1,3-bisphosphoglycerate via bisphosphoglycerate mutase. this molecule is important to regulate haemoglobin oxygen affinity
why is NAD+ so important to glycolysis
2 moles of NADH produced per glucose
also uses NAD+
if all NAD+ converyed to NADH, glycolysis would stop
normally regenerated by oxidation in metabolism but wont be in RBC as no stage 3/4 of metbaolism and if no oxygen…thus need a supply of oxygen
what enzymes regenerates NADH
lactate dehydrogenase
why would NAD+ run out/how is lactate formed
NO OXYGEN - pyruvate to lactate and no NAD+ formed
without major exercise
strenuous exercise
pathological conditions such as shock or congestive heart disease
what happens in the lactate dehydrogenase reaction
no oxygen:
increased levels of NADH and pyruvate and H+ -> NAD+ + lactate, so NAD+ regenerated for glycolysis
the NAD+ is used to restore lactate to low levels:
lactate released into blood by RBC and muscles, to liver and heart where metabolised
as there is oxygen present in these tissues, NAD+ present which with the addition of lactate can form NADH + H+ + pyruvate. NADH can then be reoxidised as oxygen present
what happens in the liver when lactate is detected
converted to pyruvate and then glucose via gluconeogenesis
if enzyme, lactate dehydrogenase is not produced
built up of lactate in the blood (lactatemia)
why would there be no lactate dehydrogenase present
vitamin deficiency
impaired in liver disease
alcohol which converts NAD+ -> NADH, then lactate could not be converted as no NAD+ present
enzyme deficiencies
where is lactate disposed fo
kidney
what is the normal concentration of lactate in the blood
below 1mM
if lactate concentration increases in the blood to 2-5mM what happens
hyperlactaemia
below renal threshold so not excreted in the urine
no change in blood pH as have enough buffering capacity
if lactate concentration increases above 5mM
lactic acidosis - critical marker in the acutely unwell
above renal threshold, appear in urine
blood pH lowered as buffering capacity not strong enough
what other sugars are metabolised in glycolysis
fructose
galactose
how is fructose metabolised in glycolysis
in liver -
acted upon by fructokinase and ATP -> ADP so phosphorylated to fructose 1-phosphate
then acted upon by aldolase to form either glyceraldehyde or DHAP
DHAP isomerised to glyceraldehyde-3-phosphate
Glyceraldehyde phosphorylated with ATP and use of triose kinase to form glyceraldehyde 3 - phospjaye so two form—-> glycolysis
what are the clinical importance of fructose
- essential fructosuria - fructokinase missing which is then means fructose is found in urine, no clinical signs
- fructose intolerance - aldolase B missing so fructose 1 - phophate builds in the liver causing damage. must be removed from diet
how is galactose metabolised in glycolysis
acted upon by galactokinase and phophorylated by ATP to form galactose 1 -phosphate
which is acted upon by uridyl transferase and the use of UDP glucose to form glucose 1-phosphate to be converted to glucose 6-hposphate -> glycolysis
UDP glucose gives one phosphate to form glucose 1 -phosphate and then galactose given as substrate to form UDP galactose, UDP galactose is then converted back to UDP glucose via UDP galactose 4-epimerase
how does galactosaemia come about
defiency in any of the enzymes involved in galactose metabolism such as galactokinase, uridyl transferase, UDP-galactose epimerase
what is galactosaemia
deficiency in galactokinase (rare) - galactose conc increase
other two enzymes deficient (common) - galactose 1 phosphate and galactose accumulates
what happens if galactosaemic and what is used as treatment
Galactose then enters other pathways. Aldose reductase converts it to galactitol and oxidised NADH to NAD+, less NADPH and structure damages caused such as cateracts
accumulation of galactose - affects liver, kidney and brain
no lactose in diet
how does galactosaemia cause cateracts
enters new pathway
levels of NADPH decrease
disulfide bridges maintained using NADH so inappropriate formation occurs, loss of structural integrity, eg: lens of eye
what is the pentose phosphate pathway
when energy levels are high and intermediatery levels of glycolysis build up glucose 6 phophate can divert out of glycolysis
what happens int he pentose phosphate pathway
glucose 6-phosphate converted to 5c sugar phosphates via glucose 6 phosphate dehydrogenase. NADP+ reduced to NADPH to oxidise reaction. Co2 is formed so irreversible = oxidative decarboxylation
then rearrangement to form glycolytic intermediates, so 3 5c sugars form 2 fructose 6-phosphate + 1 glyceraldehyde 3 phosphate
(if 5c sugar not utilised can be converted back to fructose 6-phosphate or galactose-3-phosphate and enter glycolysis)
no atp produced
controlled by coenzymes
why is NADPH important
NADPH used for providing reducing equivalent for biosynthesis
fatty acid, lipid and steroid biosynthesis - liver and adipose tissue
GSH regeneration
detoxification reactions
what can ribose 5-phosphate (5C sugar) be used for
nucleotides - lots of pathway in dividing tissue
DNA
RNA
coenzymes
what are the functions of pentose phosphate pathway
- produce NADPH in cytoplasm for biosynthesis and maintain free SH
- produce C5 sugar for nucleotides needed for nucleic acid synthesis
what happens if someone is glucose 6-phosphate dehydrogenase deficient
can not form 5C sugar phosphate
and NADPH levels fall as not being converted by reduction as no oxidation reaction
what are the affects if G6PDH deficient
NADPH not formed so not maintaining SH group of proteins
structural intergrity decreases and crossbridges inappropriate
commonly inherited
in RBC’s, aggregated proteins (misfolded) - heinz bodies - haemolysis - split so anaemia
and lens of eye
how are metabolic pathways regulated
by regulating enzymes
how does allosteric regulation of enzymes work
- the activator/inhibitor binds to another site
not to catalytic site but to regulatory site. regulatory molecule binds, confirmational change, affects catalytic activity either inhibition or activation - covalent modification - phosphorylation or dephosphorylation, alters protein conformation, alters activity
what are the principles of metabolic pathway regulation (inhibition)
i) reversible steps are not regulated, as reaction in equilibrium so levels of product unaffected. However, product inhibition can occur, if lots of product formed less substrate, so reaction reverses so more of other product formed. so reduces rate of reaction in forward direction so binding rate and catalysis reduced
ii) irreversible steps are regulated. when reduced activity - reduces flux of substrates - reduce level or product
iii) feedback pathway - prevents build up of intermediates when reaction reversed, so pathway can continue
iv) inhibition of committing step - no diversion of substrate in or out of the pathway. so if inhibited allows substate to be diverted into other pathways
catabolic pathways are inhibited by
high energy signals such as ATP, NADH, FAD2H
catabolic pathways are activated by
low energy signals such as ADP, AMP, NAD+, FAD
what is the process of hormonal regulation
- hormone receptor binding
- activates signalling pathway
- protein kinase (phosphorylation) or protein phosphotase (dephosphorylation) activated
- either phosphorylates or dephosphorylates enzyme
- alters protein conformation - either in a good or bad way
what are some examples of phosphoregulation
adrenaline - activates protein kinase A, phopshorylation activates phosphorylase kinase to form glycogen phosphorylase to stimulate glycogen breakdown
insulin - stimulates signalling pathway which activates protein phosphatase 1.
either causing dephosphorylation and activation of pyruvate dehydrogenase which stimulates glucose utilisation or dephosphorylation of glycogen phosphorylase to inhibit glycogen breakdown
what are the principles of metabolic pathway regulation (activation)
Feed forward - high levels of substrate feeds forward to pathways to activate entry of substrate into pathway by removal of intermediates
what is the key regulator of glycolysis
phosphofructokinase-1
what does PFK do
if lots of ATP and NADH - and want to store glucose as glycogen
converts fructose 6-phosphate to fructose 1,6-bisphospjate via phopshorylation of ATP -> ADP
1. when ATP levels are high and glycolysis should be inhibited, uses ATP as an allosteric site binds to it and causes inhibition (vice versa will cause activation if stimulated by high AMP when energy levels low
2. when glucose levels are high, enzyme stimulated by insulin to increase its activity (vice versa inhibited when glucagon)
what other inhibition is available for regulation of glycolysis
Hexokinase - allosteric inhibition by glucose-6-phosphate
metabolic regulation (feedback product inhibition)- high NADH or low NAD+ = high energy level signal, causes inhibition of step 5 and stops glycolysis, so flux of glucose reduced (not need it)
hormonal activation - PFK and pyruvate kinase - also sensitive to allosteric regulators. inhibited by PEP and citrate and H+ ions. Activated by fructose 2.6-bisphosphate
how is PFK regulated
phophoregulation
allosteric
how does phosphoregulation of PFK work
glucagon -> protein kinase A -> phosphorylation -> inhibition
insulin -> protein phosphatase 1 -> phosphorylation -> activation
how does phosphoregulation of pyruvate kinase work
glucagon -> protein kinase A -> phosphorylation -> inhibition
insulin -> protein phosphatase 1 -> phosphorylation -> activation
how does allosteric regulation of hexokinase work by glucose 6-phosphate
forms glucose 6 phophate is irreversible but inhibits the enzyme that forms it to prevent glucose entering glycolysis
inhibition of step 5 - high NADH = high energy level signal
inhibition of step 4 PKR in response to high energy levels
thus acts as a negative regulator of hexokinase
what are the two types of pathway regulation
metabolic
hormonal
metabolic regulation occurs when
high NADH or low NAD+ = high energy level signal -> inhibits step 5
high ATP inhibits PFK
high AMP stimulates PFK
hormonal regulation occurs when
PFK and pyruvate kinas
increase by high insulin but when glucagon high enzymes inhibited
where is the commiting step in glycolysis
phosphofructokinase inhibited
energy levels high - build up of glucose and glucose 6-phosphate to form glycogen
or to pentose phosphate pathway for biosynthesis to use ATP
whats the link reaction, what happens before krebs cycle
2 pyruvates converted to 2 acetyl coA using pyruvate dehydrogenase (made of 5 enzymes) - these require cofactors such as FAD, thiamine pyrophosphate and lipoid acid - provided by B vitamins. so reaction is sensitive to vitmain B1 defiency
in matrix, transporter from cytoplasm across matrix
pyruvate + coA + NAD+ -> acetyl coA + NADH + H+
reversible as CO2 formed so key regulatory step
what is pyruvate dehydrogenase activated and inhibited by?
activated by low energy compounds = pyruvate, coASH, NAD+, ADP, insulin - dephosphorylation of enzyme
inhibited by high energy compounds = acetyl coA, NADH, ATP, Citrate - phosphorylation of enzyme
what would happen in a deficiency of pyruvate dehydrogenase
pyruvate would build up - lactate dehydrogenase pathway - lactate - lactate acidosis
what are some key features of the krebs cycle
in mitocondria
single pathway
acetyl coA oxidised to 2CO2
requires NAD+ + FAD (pick up hydrogen atoms)
some energy produced
also produces precursors for biosynthesis
what is the krebs cycle pathway
2 acetyl coA + oxaloacetate = citrate (C6)
isomerised
isocitrate - oxidised and NAD+ reduced to NADH, and loss of CO2 (irreversible)
Decarboxylated further to 5C
5C + coA and oxidised so NADH forms (irreversible as CO2 formed)
C4 -> C4 (GDP->GTP - substrate level phosphorylation)
C4 oxidised to C4 so FAD-> FADH2
C4 -> C4 with water
C4-> oxaloacetate with NAD+ -> NADH
what is formed from the krebs cycle
3NADH (x2)
1 FAD2H (x2)
1 GDP per cycle (x2)
but 2 acetyl coA so 2 cycles
how is the krebs cycle regulated
inhibited by high energy compounds, activated by low energy compounds - at irreversible points (where CO2 released)
i) isocitrate dehydrogenase: inhibited allosterically by NADH and ATP, activated by ADP,
ii) alpha-ketoglutarate dehydrogenase: inhibited by NADH and ATP and succinyl coA, activated by ADP
whats the importance of the krebs cycle
biosynthetic processes - hub for metabolism
amino acids, glucose, fatty acids, haem, sugars, ketone body, alcohol (diff pathways in and out)
does krebs cycle function without o2
no
where is the energy carried
within NADH and FAD2H
how is water formed in metabolism
NADH is oxidised to NAD+ and in turn reduces O to H2O
what are the key features of the E.T.C and ATP synthesis?
NADH + FADH2 re oxidised
O2 required
lots of energy formed
what are the 2 process of step 4 of catabolism?
- electrons on NADH and FADH2 transferred through a series of carrier molecules to oxygen - ETC
- Oxidative phosphorylation - free energy to drive ATP synthesis
what is the structure of a mitochondria
outer mitochondrial membrane
intermembrane space
inner mitocondrial membrane
mitochondrial matrix
how does the electron transport chain work?
- NADH -> 2H+ + 2e-. electrons are picked up by protein translocating complexes on inner mitochondrial membrane. the complexes are arrnaged in sequence so electrons can be passed
- electrons passed onto next complex, and in doing so release some energy which can be used to drive protons from the mitochondrial matrix to the intermembrane space (2H+) - proton motive force due to H+ gradient
- more energy released, more protons translocated
- electron reaches third PTC, the electrons are used to form bonds between hydrogen ions and oxygen to form water
what happens after the ETC?
ATP is synthesized using proton translocating ATPase/F1F0 ATPase or ATP synthase
ATP is synthesised by energy from proton motive force when 2 protons travel back to matrix as favoured by electrochemical gradient
these protons return across membrane via ATP synthase which is what drives ATP synthesis
energy in NADH is …
more than in FAD2H (so uses 3 PTC’s in comparison to 2 as enters late)
the greater the proton motive force
more ATP synthesized
oxidation of 2 moles of NADH
5 moles of ATP (p:o 2.5)
oxidation of 2 moles of FADH2
3 moles of ATP (p:o 1.5)
ATP synthase uses
2 protons to drive synthesis of ATP
how is oxidative phosphorylation regulated
when lots of ATP and little ADP - no substrate for ATP synthase -> inward flow of H+ slows -> H+ accumulates in intermitochondrial space -> prevents further H+ PUMPING -> stops ETC
vice versa with low ATP
which inhibitors block oxidative phosphorylation
like cyanide prevents acceptance of electrons by O2 and carbon monoxide so no proton motive force so not drive ATP synthesis
what is uncoupling of oxidative phosphorylation
like dinitrophenol, disnitrocresol and fatty acids. uncouplers increase the permeability of mitochondrial inner membrane to protons, dissipate proton gradient, thus reducing PMF so no drive for ATP synthesis. ETC continues but gradient does not form
how do you inhibit ATP synthesis
- block ETC
2. prevent PMF
what genetic disorders are associated with ETC
genetic defects in proteins encoded by mitochondrial DNA
what happens to the rest of the energy
lost as heat
could lose if tightness of coupling reduced
can vary in different tissues
eg: brown adipose tissue - degree of coupling controlled by fatty acids (uncouplers) - more heat generated
what happens in brown adipose tissue
contains thermogenin - uncoupling protein
in response to cold - noradreanline activates a lipase which releases fatty acids from triacylglycerol, which releases lots of NADH/FADH2 for ETC. also activates UCP1 which transports H+ back into mitochondria matrix bypassing ATP synthases. so electron trasnprot uncoupled from ATP synthesis - energy of pmf released as heat
where is brown adipose tissue found
newborn to maintain heat around vital organs
hibernating animals
what are the differences between oxidative phosphorylation and substrate level phosphorylation
ox - requires membrnae complexes, energy coupling occurs indirectly, cannot occur in presence of O2, major process for ATP synthesis, requires lots of energy
sub - requires soluble enzymes, energy coupling occurs directly, can occur without O2, minor process for ATP synthesis, requires lots of energy
how many molecules of ATP are formed from glucose
32
If no oxygen
Only glycolysis - substrate level phosphorylation
Has to oxides baCK NADH
Under anaerobic conditions, the pyruvate produced by glycolysis in skeletal muscle may be reduced to lactate. What advantage is this to the muscle cells?
There is a fixed amount of NAD+ & NADH in the cell. The reactions of glycolysis require the presence of NAD+ which is converted to NADH. If all of the NAD+ is converted to NADH, glycolysis would stop because of lack of NAD+. This does not normally occur because, in the presence of oxygen, NADH is converted back to NAD+ by the electron transport chain in the mitochondria. However, in the absence of oxygen (anaerobic conditions) or mitochondria (red blood cell) electron transport cannot occur. Under these condition pyruvate is converted to lactate via the enzyme lactic dehydrogenase (LDH) using NADH which is oxidised to NAD+ :
CH3COCOOH + NADH + H+ ↔CH3CHOHCOOH + NAD+
This enables glycolysis to continue so that it can provide the cell with ATP via substrate level phosphorylation.
What are the possible fates of the lactate produced by skeletalmuscle under anaerobic conditions?
Lactate is released from muscle cells and carried in the blood to the liver and heart muscle. In both tissues it is converted back to pyruvate by LDH. In heart muscle the pyruvate is converted to acetyl~CoA that is subsequently oxidised via the TCA cycle to provide energy. In the liver pyruvate may also be oxidised to provide energy but most will be converted to glucose via the gluconeogenic pathway. A third possibility in the liver is oxidation to acetyl~CoA which may be used for lipid biosynthesis (fatty acids, ketone bodies or cholesterol)
Define lactic acidosis and explain why it may occur.
Lactic acidosis is an elevation of plasma lactate that affects the buffering capacity of the plasma i.e. there is a fall in plasma pH due to the accumulation of lactic acid. Situations in which there may be a marked increase in plasma lactate due to increased production include strenuous exercise (up to 10g/min), hearty eating, shock and congestive heart disease. Increases due to decreased utilisation occur in liver disease, thiamine deficiency and during alcohol metabolism.
Interpret the observation that the enzyme phosphofructokinase in skeletal muscle is inhibited by high concentrations of ATP and activated by high concentrations of AMP.
Key catabolic enzymes are activated by low energy signals (signals that indicate a low energy status in the cell) and inactivated by high- energy signals (signals that indicate a high energy status in the cell). Opposite for key anabolic (biosynthetic) enzymes. AMP is a low-energy signal that activates phosphofructokinase and speeds up glycolysis so that more ATP can be produced. ATP is high-energy signal that inhibits phosphofructokinase and slows down glycolysis as enough ATP is available.
Compare and contrast the functions of glycolysis in adipose tissue,
skeletal muscle and red blood cells.
Glycolysis is used to produce ATP by substrate level phosphorylation in all three tissues:
• In red blood cells it is the only mechanism for ATP production.
• In skeletal muscle it enables ATP production to occur under
anaerobic conditions. • In adipose tissue it is a minor route for ATP production.
Glycolysis is used to produce useful intermediates in red blood cells and adipose tissue:
• 2,3-bisphosphoglycerate is produced from 1,3-
bisphosphoglycerate in red blood cells and is important in regulating (decreases) the oxygen affinity of haemoglobin.
• Glycerol phosphate is produced from dihydroxyacetone
phosphate in adipose tissue and is used in the esterification of fatty acids to produce triacylglycerol.
- List the end-products of glycolysis under aerobic and anaerobic
conditions in red blood cells and skeletal muscle.
Aerobic conditions Anaerobic conditions
Lactate Lactate red blood cells
PyruvateLactate skeletal muscle
Outline the important roles of pyruvate dehydrogenase in glucose metabolism.
The PDH reaction cannot be reversed in the cell. There are two major consequences of this: • The loss of CO2 from pyruvate is irreversible. • Acetyl~CoA cannot be converted to pyruvate and therefore cannot be
converted to glucose. The reaction is therefore subject to control mechanisms that ensure: • Acetyl~CoA from the b-oxidation of fatty acids rather than from glucose is
used in stage 3 of catabolism (acetyl~CoA inhibits the enzyme
allosterically). • The reaction is sensitive to the energy status of the cell (ATP and NADH
inhibit and ADP activates the enzyme allosterically). • The enzyme is activated when there is plenty of glucose to be catabolised
(insulin activates the enzyme by promoting its dephosphorylation).
What happens if not had dairy for a while
lactase deficiency.
Some adults suffer from this disease due to the loss of lactase (ß-
galactosidase) activity and hence the ability to hydrolyse lactose (milk
sugar) to glucose and galactose. As a result, the unhydrolysed lactose is
fermented by gut bacteria to form various organic acids that irritate the
gastro-intestinal tract, causing cramps and diarrhoea. These symptoms
last until all of the lactose has been metabolised and the products
removed, i.e. about 24 hr.
what are the symptoms of galactosaemia
vomiting after drinking milk cataracts damaged liver urine has high sugar jaundice
what tissue is responsible for the major part of galactose metabolsim
galactokinase
uridly transferase
UDP-galactose epimerase
if no galactokinase, build up of…..which causes…
just galactose
cataracts
sugar in urine
no damage to liver
if no uridyl or epimerase, build up of….which causes
Galactose and galactose 1 P
cataracts
liver function lost
how to distinguish if the body has not got uridyl or epimerase
epimerase - rare and if do not have then can not undergo glycogenesis so can’t make galactose from glucose
how would you determine which enzyme was missing in a person
blood sugar test enzyme assay (blood sample)
why would galactose be present in the urine
no enzyme present so won’t be broken down
if damage liver + reaches kidney threshold
what are the metabolic consequences of the absence of galactose 1-P transferase
build up of galactose - conversion of galactose to galactilol - results in galactasamia
why do galacatosaemic patients develop cataracts
increased activity of aldose reductase -> NADPH less -> defences worst -> oxidative damage -> crystallin protein in eye damaged -> cataracts
why does a galactosaemic patient become jaundiced
RBC’s broken down in spleen -> forms billirubin which is taken to the liver. due to damage of liver - unable to be excreted so builds up and causes yellowing
is there an alternative source of tissue galactose for patients on a galactose free diet
galactose can be formed from glucose
glucose -> glucose BP -> glucose 1P -> UDP glucose -> UDP galactose -> galactose
would a mother who is galactosaemic be able to produce lactose in her milk
can form lactose from glucose
UDP galactose + glucose (lactose synthase) ->lactose + UDP
what happens in pesticide poisoning
2,4-DNP penetrates the mitochondrial inner membane and act as uncoupling agents. less energy from ox Ph so energy lost as heat and body temp rises. to combat - increased sweating -> coma-> death
why is cyanide toxic to cells
blocks NADH and FAD2H oxdiation- no proton motive force - no ATP synthesis - cell death
compare and contrast oxidative phosphorylation and substrate level phosphorylation
Oxidative phosphorylation
• Produces ATP from ADP and Pi
• Requires membrane associated complexes (inner mitochondrial
membrane) • Energy coupling occurs indirectly through generation and
subsequent utilisation of a proton gradient (p.m.f). • Cannot occur in absence of oxygen. • Efficiency of energy conservation ~33% - considerable heat
production • Major process for ATP synthesis in cells that require large amounts
of energy.
Substrate level phosphorylation
• Produces ATP from ADP + phosphorylated organic compound.
• Requires soluble enzymes (cytoplasmic and mitochondrial matrix)
• Energy coupling occurs directly through formation of a high energy
of hydrolysis bond (phosphoryl-group transfer). • Can occur to a limited extent in absence of oxygen. • Efficiency of energy conservation ~60% - low heat production. • Minor process for ATP synthesis in cells that require large amounts
of energy.
