Metabolism - Lec 3

Question 1

other things such as fats can feed into and OUT OF glycolysis, which 2 do you need to know about?

Answer 1

Fats - glycerol phosphate

2,3 - bisphophoglycerate (produced in RBC’s)

Question 2

explain the purpose of glycerol phosphate in glycolysis

Answer 2

glyceraldehyde feed out of glycolysis pathway by converting to DHAP

DHAP is converted to Glycerol Phosphate using a NAD+ to NADH reduction and glycerol 3 - phosphate dehydrogenase enzyme

glycerol phosphate is then convertied to Triglyceride (FATS) using fatty acids

this is vital in fat storage and phopholipid (bilayers) syntheis

Fat produced in adipose and liver

Question 3

explain the purpose of (2,3-BPG) 2,3 bisphosphoglycerate phosphate in glycolysis

Answer 3

1,3 BPG is part of the glycolysis pathway

it is converted to 2,3 - BPG by Bisphosphoglycerate mutase

this is done in RBC’s

is a regulator of haemoglobin affinity (promotes release of O2)

Question 4

why do we need lacatae dehydrogenase (LDH) ?

Answer 4

glycolysis produces 2x NADH, so it needs NAD+
this is at constant levels within cells
Normally we regenrate the NAD+ in stage 4 of catabolsim

However RBC’s have no stage 3 or 4, stage 4 also relises on O2, sometimes we dont have much O2

so we need an alternative pathway to regenrate NAD+
this is using LACTATE DEHYDROGENASE (LDH)

Question 5

how does the LDH cycle work , why do we need it ?

Sketch it on paper

Answer 5

Lactate Dehydrogenase (LDH) is used in a reversible reaction

NADH + H+ + Pyruvate NAD+ + Lactate
LDH

Here NAD+ is regenerated, this is done when o2 is low or in RBC’s
as opposed to stage 4 (regens NAD+ when O2 is high)

lactate is then transported to liver and heart via blood
liver and heart have high O2 concs naturally, as very active organs
(can effecitvley regen NAD+ using stage 4)

lactate in blood and liver can use NAD+ ——> to NADH and LDH in reverse to produce Pyruvate

Pyruvate can then be oxidated to give ATP (energy) via normal catabolic glycolysis - as they have high O2

in live an alternate option is to undergo gluconeogenesis - this produces glucose, can be sent via blood to normal tissues for normal glycolysis when O2 is high in conc again.

Question 6

how is plasma lactate conc used clinically ?

Answer 6

Lactate is acidic (think stich via lactic acid during exercise)

normal conc - 1mM

hyperlactaemia - 2-5mM
No change in Blood PH due to buffer system
happens during hard exercise ect

Lactic Acidosis - above 5Mm
lowers blood pH as past buffering ability
this is a key marker in actuley unwell patient

Question 7

how does fructose feed into glycolyisis?

Answer 7

through a series of steps fructose is broken into glyceraldhdye-3-phosphate, which is a part of glycolysis so it feed in.

if aldolase (converter enzyme is missing) toxic build up in liver, remove fructose from diet (extra)

Question 8

how does galactose feed into metabolism ?

review group work well on this.

Answer 8

galactose is half of the lacotse disaccharide from milk

all sugars feed into the early steps of glycolysis

3 enzymes involved -
galktokinase - galactose - adds phosphate - galactose 1-P

Uridyl transferase - converts galactose 1-P to glucose 1-P which can feed into glycolysis via glucose 6-P

UDP - galactose empirase - swaps a galactose for glucose
it can then take this galactose and convert it into glucose through some steps, to be useful.

a deficiency in any of these enzymes can cause galactosemia.

Question 9

what is galactosemia ?

review group work well on this.

Answer 9

inability to utilise galactose, due to enzyme deficiency
galactokinase - galactose accumulates
transferase - galactose and galactose 1-P accumulate

this causes galactose to enter other pathways

can be reduced to galactitol by oxidising NADPH using aldose reductase
this depletion of NADPH prevents maintenance of free sulphydryl groups on proteins, we get disulphide bonds forming as a result of the reaction
this causes a loss of structure and function of some proteins

can cause structural damage to lens of the eye - cataracts - eye cloudiness

acumulation of Galactose 1 - P afttects liver - galacotse 1-P build up - toxic to liver - liver enlarges - jaundice is noticed due to release of billirubin from liver. liver is damaged

galactose 1-P builds up and causes systemic damage to organs.

kidney and brain

treatment is no lactose in the diet

Question 10

explain the pentose phosphate pathway

Answer 10

the pathway is triggerd by inhibition of glycolysis due to high energy signals - NADH and ATP

glucose 6-P dehydrogenase converts glucose 6-P to a intermediate - it is the rate limiting enzmye

this reduces NADP+ to NADPH
converts C6 to C5 -producing CO2 in the process

the C5 intermediate can feed into glycolysis via fructose 6-P or glyceraldehyde 3-P via some steps

the final result is a ribose 5-P (5C) with CO2 produced and NO ATP made

the production of NADPH is very important as -

1. bio synthetic reducing power ie lipid synthesis
2. Maintaining Free SH bonds on protiens by preventing oxidation to disulphide bonds
3. C5 ribose produced provides the sugar phospahte backbone for DNA and RNA and neucleotides

Question 11

what happens if we have a glucose 6-phosphate dehydrogenase (G6DPH) deficiency?

Answer 11

we no longer produce enough NADPH

cannot maintain the free SH bonds vital to structure and function of some proteins.
disulphide bonds form.

this has effects across the body -
cataracts in lens of the eye
haemolysis in RBCs - SH bonds vital to strucutre -causes heinz bodies (aggregation)