Energy Production: Carbphydrates Flashcards

Question

Describe step 6

Answer 1

• 2 moles of NADH produced per mole of glucose • Pathway therefore requires NAD+ • Total NAD+ + NADH in cell is constant, therefore, glycolysis would stop when all NAD+ is converted to NADH • Normally, NAD+ is regenerated from NADH in stage 4 of metabolism (see Lecture 4) BUT 1. RBC have no stage 3 or 4 of metabolism 2. Stage 4 needs O2 - supply of O2 to muscles and gut often reduced • Therefore, need to regenerate NAD+ by some other route Lactate Dehydrogenase (LDH)

Answer 2

Produced from glucose (and alanine) via pyruvate • without major exercise 40 - 50 g/24 hours – RBC, skin, brain, skeletal muscle, G.I. tract • Strenuous exercise (includes hearty eating!) 30 g/5 min – Plasma levels x 10 in 2 - 5 min – Back to normal by 90 min • Pathological situations, e.g. – SHOCK – CONGESTIVE HEART DISEASE

Answer 3

NADH + H+ + pyruvate NAD+ + lactate CH3COCOOH -> CH3CHOHCOOH Catalysed by LDH • Lactate by liver and heart (via LDH) • produced by RBC and skeletal muscle (skin, brain, GI) • Released into blood and • normally metabolised by liver and heart • Liver and heart need NAD+ to be regenerated efficiently, usually well supplied with oxygen Keeps glycolysis running

Answer 4

RBC, skeletal muscle (skin, brain, GI) In low O2 conditions pyruvate converted to lactate instead of stage 4 of metabolism which requires O2 Impaired in liver disease Vitamin deficiency - thiamine Alcohol NAD+ -> NADH Enzyme deficiencies

Answer 5

Plasma concentration determined by relative rates of 1. production 2. utilisation (liver, heart, muscle) 3. disposal (kidney)

Answer 6

Hyperlactaemia • 2 - 5 mM • Below renal threshold • No change in blood pH (buffering capacity) Lactic acidosis • above 5 mM • Above renal threshold • Blood pH lowered

Answer 7

Fructose = fruit monosaccharide Glucose-fructose disaccharide Metabolised in liver in human ``` Clinical Importance 1. Essential fructosuria - fructokinase missing • Fructose in urine no clinical signs 2. Fructose intolerance - aldolase missing • Fructose-1-P accumulates in liver - leads to liver damage • Treatment? - remove fructose from diet ```

Answer 8

Lactose, dissacharide in milk, galactose + glucose Metabolism in liver (major tissue) UDP-glucose acts catalytically Clinical importance - Galactosaemia - 1 in 30,000 births

Answer 9

Autosomal recessive disorder which affects how the body processes galactose Deficiency in any of the enzymes galactokinase, uridyl transferase or up-galactose epimerase can cause it Milk rich diet - infancy Unable to utilise galactose Galactokinase deficiency (rare) - galactose accumulates Transferase deficiency (common) - galactose and galactose-1-P accumulate Problem • Galactose enters other pathways Galactose —> galactitol (NADPH -> NADP+) Catalysed by aldose reductase * depletes lens of NADPH - structure damaged - cataracts * Accumulation of galactose-1-P affects liver, kidney, brain - How? * Treatment - no lactose in diet * Raised galactose concentration enters new pathways * Depletes NADPH levels * Prevents maintenance of free sulphydryl groups on proteins * Inappropriate disulphide bond formation * Loss of structural and functional integrity of some proteins that depend on free -SH groups * E.g. lens of eye

Answer 10

Series of non-oxidative reactions convert 5C sugars into 6C and 3C sugars which can be utilised by glycolysis All enzymes in cytosol 2 stages 1) oxidative decarboxylation Glucose-6-p —-> C5 sugar + CO2 (NADP+ —> NADPH) 2) rearrangement to glycolysis intermediates 3 C5 sugars ——> 2 f6P + 1 glyceralddehyde-3-p No atp production Loss of co2 to irreversible Controlled by NADP+/NADPH ratio at G6P dehydrogenase

Answer 11

1. produce NADPH in cytoplasm (a) Biosynthetic reducing power e.g. lipid synthesis therefore, high activity in liver and adipose tissue (b) Maintain free -SH (cysteine) groups on certain proteins Prevent oxidation to - S - S - (disulphide bonds) 2. Produce C5 sugar for nucleotides needed for nucleic acid synthesis Therefore, high activity in dividing tissues e.g. bone marrow

Answer 12

* Pentose phosphate pathway has an important role in providing NADPH to maintain SH group of proteins in a reduced state * Structural integrity and, hence, functional activity of some proteins depends on free -SH groups * G6PDH deficiency is a very common inherited defect * e.g. in RBC, low NADPH -> disulphide bonds formed -> aggregated proteins, Heinz bodies -> haemolysis * Lens of eye

Answer 13

``` • Starts from Glucose-6-phosphate • Important source of NADPH required for: • Reducing power for biosynthesis • Maintenance of GSH levels • Detoxification reactions • Produces C5-sugar ribose required for synthesis of : • Nucleotides, • DNA & RNA. • No ATP synthesised. CO2 produced • Rate limiting enzyme is: Glucose 6-phosphate dehydrogenase LEARN PRINCIPLES ONLY: No need to memorise entire pathway! ```

Answer 14

• Mitochondrial matrix (pyruvate transported from cytoplasm across mitochondrial membrane) • PDH is a large multi-enzyme complex (5 enzymes) • The different enzyme activities require various cofactors (FAD, thiamine pyrophosphate and lipoic acid). B-vitamins provide these factors, so reaction is sensitive to Vitamin B1 deficiency. • Reaction is irreversible, so is a key regulatory step. • Irreversible loss of CO2 • Pyruvate cannot be formed from acetyl-CoA • Large multi-enzyme complex • Irreversible reaction • Subject to multiple regulation • PDH deficiency – lactic acidosis

Answer 15

* Mitochondrial * A single pathway – * Acetyl (CH3CO-) converted to 2CO2 * Oxidative (requires NAD+, FAD) * Some energy produced (as ATP/GTP) * (Also produces precursors for biosynthesis)

Answer 16

Citrate (c6) - > c6 - > isocritate (c6) - > (nad+ to nadh, co2 released) c5 - > (coA in, nad+ to nadh, co2 released) c4 - > (gdp to gtp, coA out) c4 - > (fad to fadh2) c4 - > (H2O in) c4 - > (nad+ to nadh) c4 - > c4 + acetyl coA (c2) from link, makes citrate

Answer 17

• Regulated by energy availability, i.e. ATP/ADP ratio and NADPH/NAD+ ratio Irreversible steps - release co2 Regulated by energy containing molecules Adp is a low energy signal - stimulates Enzymes: isocritate dehydrogenase, a-ketoglutarate dehydrogenase

Answer 18

Mitochondrial • Central pathway in the catabolism of sugars, fatty acids, ketone bodies, amino acids, alcohol • Strategy - to produce molecules that readily lose CO2 • Breaks C-C bond in acetate (acetyl~CoA); carbons oxidised to CO2 • Oxidative producing NADH and FADH2 • Some energy as GTP (~= ATP) produced directly • Produces precursors for biosynthesis • Does not function in absence of O2 (c.f. electron transport chain) • Intermediates act catalytically - no net synthesis or degradation of Krebs cycle intermediates alone

Answer 19

* Mitochondrial * Electron transport and ATP synthesis * NADH & FADH2 re-oxidised * O2 required (reduced to H2O) * Large amounts of energy (ATP) produced

Answer 20

Two processes 1. Electrons on NADH and FAD2H transferred through a series of carrier molecules to oxygen (ELECTRON TRANSPORT) Releases energy in steps 2. Free energy released used to drive ATP synthesis (OXIDATIVE PHOSPHORYLATION)

Answer 21

• Electrons are transferred through series of carrier molecules (mostly within proteins) to O2, with release of energy. • ~30% of energy used to move H+ across membrane (a lot of the energy released as heat.) • [H+] gradient (membrane potential) across inner mitochondrial membrane caused by energy of electrons = proton motive force PTC = protein translocations complex

Answer 22

ATP synthase Uses hydrogen ion gradient to drive the synthesis of atp Giving up energy of proton gradient • Return of protons (H+) is favoured energetically by the electrochemical potential (electrical and chemical gradient) • Protons (H+) can only return across membrane via the ATP synthase and this drives ATP synthesis

Answer 23

• Electrons are transferred from NADH and FAD2H to molecular oxygen • Energy released is used to generate a proton gradient, proton motive force (pmf) • Energy from the dissipation of the proton motive force is coupled to the synthesis of ATP from ADP * Electrons in NADH have more energy than in FAD2H, * so NADH uses 3 PTCs, FADH2 uses only 2. * The greater the p.m.f. -> more ATP synthesized * Oxidation of 2 moles of NADH -> synthesis of 5 moles of ATP (P/O = 2.5) * Oxidation of 2 moles of FADH2 -> synthesis of 3 moles of ATP (P/O = 1.5)

Answer 24

• When [ATP] is high, i.e. [ADP] is low, so no substrate for ATP synthase (synthetase) • so inward flow of H+ stops • Concentration of H+ in the intermitochondrial space increases • Prevents further H+ pumping - stops electron transport • Normally oxidative phosphorylation and electron transport are tightly coupled • Both regulated by mitochondrial [ATP] • High ATP = Low ADP • When [ADP] is low, so no substrate for ATP synthase (synthetase) • so inward flow of H+ stops • Concentration of H+ in the intermitochondrial space increases • Prevents further H+ pumping - stops electron transport • Reverses with low [ATP]

Answer 25

• Inhibitors block electron transport, e.g. cyanide (CN-) prevents acceptance of electrons by O2 Bind with higher affinity than oxygen - reduced h+ translocation reduces pmf - synthesis of ATP reduced - leads to cell death No electron transport - Block the whole of oxyphos and all of catabolic * Uncouplers increase the permeability of the mitochondrial inner membrane to protons - h+ enter mitochondria without driving ATP synthase * dissipate the proton gradient, thereby reducing the proton motive force * No drive for ATP synthesis

Answer 26

Genetic defects in proteins encoded by mtDNA (some subunits of the PTCs and ATP synthase) so decrease in electron transport and ATP synthesis

Answer 27

* What happens to the rest of the energy ? * Lost as HEAT * Efficiency depends on tightness of coupling * Can be varied in some tissues * Brown adipose tissue - degree of coupling controlled by fatty acids (uncouplers) - allows extra heat generation

Answer 28

Contains thermogenin (UCP1) - naturally-occurring uncoupling In response to cold, noradrenaline (norepinephrine) activates : 1. Lipase which releases fatty acids from Triacylglycerol 2. Fatty acid oxidation -> NADH/FADH2 -> electron transport 3. Fatty acids activate UCP1 4. UCP1 transports H+ back into mitochondria So, Electron Transport uncoupled from ATP Synthesis. Energy of p.m.f. is then released as extra heat. Family of UCPs – role in heat generation by uncoupling but may have other functions.

Answer 29

Newborn infants to mainatain heat around vital organs | Hibernating animals to generate heat to maintain body temp

Answer 30

Oxy Requires membrane-associated complexes (inner mitochondrial membrane) Energy coupling occurs indirectly through generation & subsequent utilisation of a proton gradient (pmf) Cannot occur in the absence of O2 Major process for ATP synthesis in cells requiring large amounts of energy Sub Requires soluble enzymes (cytoplasmic & mitochondrial matrix) Energy coupling occurs directly through formation of high energy of hydrolysis bond (phosphoryl-group transfer) Can occur to a limited extent in the absence of O2 Minor process for ATP synthesis in cells requiring large amouts of energy

Energy Production: Carbphydrates Flashcards

(55 cards)