In the carbohydrate metabolism part two we saw that the end of the glycolysis is pyruvate and also NADH which is obtained in step 6, but we don’t know the fate of pyruvate and NADH; will they be waste products or will they consumed in any way? ………. this what we see in this part
Also, we will study the importance of glycolysis and the diseases resulted from the deficiency of the 3 enzymes that catalyze the 3 irreversible steps
A) Fate of Pyruvate and NADH
We know before that in the step 5, Dihydroxyacetonephosphate (DHAP) and glyceraldehyde-3-Phosphate (G-3-P) are produced and also we know that the cell doesn’t consume DHAP, so, DHAP is converted into G-3-P……….thus,the stage 2 of glycolysis starts with 2 G-3-P and thus we get 2 NADH and 2 Pyruvate from the stage 2 (the end of glycolysis) >>>>>> and we know that the conversion of DHAP to G-3-P occurs to get the energy from the 6 carbons of glucose
But also pyruvate has 3 carbon and the cell doesn’t get energy from them, …….. so, what is the fate of pyruvate? …..Will the cell get rid of it as waste product and lose the energy of 3 carbons? ….. this what we will see in this section.
In case of NADH, What is its fate? ….. it should be converted to NAD+ which is needed in the step 6 and if this conversion doesn’t occur, glycolysis can’t be repeated because there will not be enough NAD+……. so NADH should be oxidized through Krebs cycle and Electron transport chain or by fermentation in case of oxygen shortage (we will study this in the next lectures).
1) Fate of Pyruvate:
Pyruvate will be oxidized to get the energy of the rest 3 carbons …. in 2 ways:
Oxidation in presence of Oxygen through Krebs cycle (Tricarboxylic acid cycle [TCA]) and Electron Transport chain (ETC) in Mitochondria.
Oxidation in absence of Oxygen to be converted into lactate
a) Under aerobic conditions (in presence of oxygen):
In aerobic conditions, pyruvate proceeds through the tricarboxylic acid (TCA) cycle (=Kerbs cycle) to complete glucose oxidation by its conversion to acetyl CoA and oxaloacetate which are the principle intermediates for of kreb’s cycle ….. let’s see the fate of pyruvate:
i. Oxidation to acetyl-CoA:
In presence of oxygen, pyruvate is oxidized to acetyl-CoA (acetyl coenzyme A) producing much more energy by Pyruvate dehydrogenase via oxidative decarboxylation reaction as follow:
Here, a carboxyl group is removed and replace by a Co-enzyme A to get acetyl coA
Acetyl-CoA is a major fuel for krebs cycle as well as a building block for fatty acid synthesis in mitochondria.
ii. Carboxylation to oxaloacetate:
Conversion of pyruvate to oxaloacetate (OAA) by pyruvate carboxylase is an important, because it provide the citric acid cycle with OAA intermediate and provides substrate for gluconeogenesis and krebs cycle.
Here, a carboxyl group is added on the CH3 group
b) Under anaerobic conditions:
If no oxygen is available or in case of short supply of oxygen, cells can obtain energy through the process of anaerobic respiration such as fermentation, producing lesser energy than aerobic respiration in the form of fewer ATP molecules and it is not efficient process.
In an aerobic condition, glycolysis is repeated when the NAD+ is regenerated in the kerbs cycle and electron transport chain by oxidising NADH resulting in high energy, but in case of anaerobic respiration glycolysis is self-functioning through regeneration of NAD+ by the conversion of Pyruvate to lactate by lactate dehydrogenase through lactic acid fermentation process without producing any ATP molecules.
This conversion of Pyruvate to lactate in anaerobic conditions is promoted by the accumulation of NADH and the depletion of NAD+ which is needed as an electron acceptor so that glycolysis can continue
In microorganisms, NAD+ is regenerated through conversion of Pyruvate to ethanol by ethanol dehydrogenase through the alcohol fermentation.
Tissues that use lactic fermentation:
1) RBCs: because it doesn’t contain mitochondria because aerobic oxidation of pyruvate occurs through Kerbs cycle and electron transport chain in mitochondria
2) Muscles: during heavy exercise the oxygen need to get energy is less than that supplied to the cells thus there is a shortage of oxygen supply, thus the muscle get energy through anaerobic glycolysis and regenerate NADH through the lactic acid fermentation (anaerobic respiration).
2) Fate of NADH:
a) In aerobic conditions:
NADH is re-oxidized in the electron transport pathway and kerbs cycle, making 6ATPs molecules in oxidative phosphorylation, thus in the aerobic respiration, the cell get 8ATPs;
8ATP = 6 ATP form the electron transport chain + 2 ATP from glycolysis .
we will study kerbs cycle and electron transport chain in the next lectures.
b) In anaerobic conditions:
NADH is re-oxidized by lactate dehydrogenase (LDH) or alcohol dehydrogense either of which provide NAD+ for more glycolysis.
See interpretation of some body conditions after struding glycolysis in page 2