ANS 330 Glycolysis (Carbohydrate Catabolism)

Glycolysis

second most available method for producing ATP for muscle contraction, anaerobic breakdown of glucose (anaerobic glycolysis)

What is glycolysis?

a series of 10 enzymatically controlled chemical reactions, from glycogen (to pyruvate) to lactate

What is the net production of ATP for glycolysis?

2 ATP molecules, 1 glucose --> 2 lactate

What is the net production of ATP for glycogen to lactate?

3 molecules of ATP

What has to happen before glucose/glycogen can be used to generate ATP?

conversion of glucose to Glucose-6-Phosphate

Is there an addition or loss of ATP when glucose is converted to G-6-P?

loss of 1 ATP

What happens during the conversion of glycogen?

G-6-P formed from G-1-P, no energy expenditure

Steps from glycogen to G-6-P and their enzymes

Glycogen -->(glycogen phosphorylase) G-1-P -->(phosphoglucomutase) G-6-P

glycogenolysis

breakdown of glycogen

What does glycolysis ultimately produce?

pyruvate

What determines the fate of pyruvate?

the use of O2. without O2 it turns in to lactic acid (quickly converted to lactate), with O2 it turns in to acetyl-CoA

What can occur simultaneously within the same cell?

anaerobic and aerobic glycolysis, there is an overlap of anaerobic and aerobic metabolism

What is the ratio of lactate to pyruvate formation?

depends on many factors and not just O2, enzyme kinetics (how rapidly the enzyme is functioning), mitochondrial capacity of cell, hormonal control (insulin, glucagon), required rate of energy production

What happens when glucose enters the muscle cell?

irreversible phosphorylation reaction occurs, glucose --> Glucose-6-Phosphate via hexokinase

Why is G-6-P now trapped in the cell?

phosphorylated sugars do not penetrate cell membranes, glucose is now committed to further metabolism

What enzyme is responsible for the phosphorylation of glucose?

Hexokinase (HK)

What kind of enzyme is HK considered?

it is considered a regulatory enzyme of glycolysis (1 of 3)

How is the phosphorylation of glucose rate limiting?

rate of glucose flux through the glycolytic pathway is controlled by rate at which glucose is phosphorylated in the HK rxn

What is HK activated by?

high levels of glucose

What is HK inhibited by?

elevated levels of ATP and G-6-P

What happens to ATP during the HK rxn?

1 mole of ATP is expended

What happens to energy throughout glycolysis?

Energy is expended before yield has occurred

What is the second reaction to take place and what happens during it?

the second reaction is an isomerization rxn. conversion of G-6-P to F-6-P

What is the third reaction that takes place and what happens during it?

the third reaction is phosphorylation. conversion of F-6-P to F-1,6-P via phosphofructokinase (PFK). another ATP is expended

What is important about phosphofructokinase?

it is the most important rate-limiting enzyme in glycolysis

What is PFK allosterically controlled by and does it increase or decrease the rate of reaction?

[ATP] decreases, [F-6-P] increases, citrate decreases, ADP increases, AMP increases

Glyceraldehyde 3-phosphate

everything is duplicated, gone from 6-C molecule to two 3-C molecules

What is Glyceraldehyde 3-phosphate converted to?

1,3-diphosphoglycerate, NAD+ accepts H+ ion and is reduced to NADH

How will NADH be reoxidized back to NAD+?

either by conversion of pyruvate to lactate or through oxidation in the respiratory chain

What is 1,3-diphosphoglycerate dephosphorylated to and what happens during this reaction?

it is converted to 3-phosphoglycerate and 1 ATP is formed (technically 2 since this is happening twice)

What is the ATP production up to this point?

ATP is "even" in production and use

What happens when Phosphoenolpyruvate (PEP) is converted to pyruvate?

it is converted via pyruvate kinase (PK) and ATP is produced (2)

What activates PK?

F-1,6-bisphosphate activates PK, feed forward control, link two kinases together

What is the PK rxn?

it is the third regulatory reaction of glycolysis, net ATP production is now 2

What happens during heavy exercise (anaerobic metabolism)?

pyruvate converted to lactate, this glycolytic ATP production can continue only if NAD+ is recycled, oxidizing NADH to NAD+

What ratio favors lactate production?

High NADH/NAD+ ratio

How does lactate cause muscle fatigue?

if it accumulates in muscle (H+)

What is acidification of muscle fibers?

inhibits further glycogen breakdown, it impairs glycolytic enzyme function, acts as a protective method

What can lactate decrease?

it can decrease fiber's Ca2+ binding capacity, which impedes muscle contraction

What can happen after lactate diffuses into blood?

converted to glucose in the liver, oxidized in the heart

What is the overall equation for glycolysis from glucose to lactate?

Glucose + 2 ADP + 2 Pi --> 2 Lactate + 2 ATP + 2 H2O