GLYCOLIYSIS
o Also known as______ pathway
o Employed by all tissues for the breakdown of glucose to provide some energy (in the form of ATP)
o Takes place in the cytoplasm
GLYCOLYSIS (EBDEN-MEYERHOF)
TYPES OF GLYCOLYSIS
1. AEROBIC GLYCOLYSIS
2. ANAEROBIC GLYCOLYSIS
o Needs adequate supply of oxygen
o Pyruvate is the end product of the reaction
o It sets the stage for the oxidative decarboxylation of pyruvate to acetyl CoA, a major fuel of the citric acid cycle (kreb’s cycle)
1. AEROBIC GLYCOLYSIS
Over all reaction of AEROBIC GLYCOLYSIS
Glucose + 2 Pi + 2 NAD + 2 ADP------>2 pyruvate + 2 ATP + 2 NADH + 2 H + H2O
o Needs adequate supply of oxygen
o Pyruvate is the end product of the reaction
o It sets the stage for the oxidative decarboxylation of pyruvate to acetyl CoA, a major fuel of the citric acid cycle (kreb’s cycle)
2. ANAEROBIC GLYCOLYSIS
Over all reaction ANAEROBIC GLYCOLYSIS:
o Glucose + 2 Pi + 2 ADP------>2 lactate + 2 ATP + 2 H2O
The conversion of glucose to pyruvate occurs in two phases
1. ENERGY INVESTMENT PHASE
2. ENERGY GENERATION PHASE
• The first five reactions of glycolysis where phosphorylation of glucose and fructose are synthesized at the expense of ATP, which is converted to ADP (see diagram below)
1. ENERGY INVESTMENT PHASE
• This corresponds to the last five reactions where a net of two molecules of ATP are formed per glucose molecule metabolized. Two molecules of NADH are formed when pyruvate is produced (aerobic glycolysis) whereas NADH is reconverted to NAD when lactate is the end product (anaerobic glycolysis).
2. ENERGY GENERATION PHASE
TOTAL ATP PRODUCED PER MOLECULE OF GLUCOSE IN AEROBIC GLYCOLYSIS:
8 ATPs
TOTAL NUMBER OF ATP PRODUCED PER MOLECULE OF GLUCOSE IN ANAEROBIC GLYCOLYSIS:
2 ATP
There are three irreversible reactions in glycolysis:
There are three irreversible reactions in glycolysis:
1. Glucose --- hexokinase---> glucose-6-phospshate
2. Fructose-6-phosphate --- phosphofructokinase---> fructose-1,6-bisphosphate. (this is the regulating step or rate limiting reaction of glycolysis).
3. Phosphoenolpyruvate (PEP)--- pyruvate kinase---> pyruvate
Regulatory enzymes
These enzymes occur in irreversible reactions. These include: ____________, and regulate glycolysis.
1. hexokinase
2. phosphofructokinase
3. pyruvate kinase
Found in the liver.
Catalyzes glucose phosphorylation in the first step of glycolysis in the liver.
Insulin facilitates its actions.
High Km and high Vm .
Primary responsibility is to handle increased post-meal glucose surge.
• Glucokinase
In every cell of the body.
Less specific; it can phosphorylate different hexose i.e., mannose, fructose, glucose.
Inhibited by glucose-6-phosphate.
Has low Km –high affinity so can continue phosphorylization even when low glucose levels are low.
Catalyzes glucose phosphorylation, in first step in glycolysis.
Catalyzed reaction is irreversible.
Hexokinase is able to phosphorylate all: D-glucose, D-mannose, and D-fructose.
• Hexokinase
- Is the rate limiting reaction.
- Actions are facilitated by high concentrations of AMP, and by fructose 2,6-biphosphate.
- Inhibited by citrate, high concentration of ATP,
Phosphofructokinase
HORMONAL REGULATION
_______ stimulates glycolysis through increasing the activity of glucokinase, phosphofructokinase, pyruvate kinase
Insulin
HORMONAL REGULATION
_______inhibit glycolysis through decreasing the activity of glucokinase, phosphofructokinase pyruvate kinase
Glucagon
o Inherited glycolytic enzyme deficiencies
Examples:
Pyruvate kinase (95 % of cases) deficiency
Glucosephosphate isomerase deficiency (4 % of cases)
• Most common manifestation is _________which is the result of premature death and lysis of red blood cells because of inadequate ATP synthesis.
HEMOLYTIC ANEMIA
The condition typically occurs when cells receive too little oxygen (hypoxia). During this situation, cells are forced to metabolize glucose anaerobically (anaerobic glycolysis) to supply its energy (ATP), which leads to lactate formation.
o Lactic acidosis
The most common cause of lactic acidosis is _______. The symptoms include a burning feeling in your muscles, cramps, nausea, weakness, and feeling exhausted. It is temporary. It happens when too much acid builds up in your bloodstream. It is your body's way to tell you to stop what you are doing.
intense exercise
Some medical conditions can also bring on lactic acidosis, including:
• Respiratory failure
• Seizures
• Liver failure
• Sepsis (a whole-body inflammation caused by severe infection)
• Shock