Intermediate Metabolism- glycolysis

Question 1

What is glycolysis?

Answer 1

It is the pathway that converts glucose to Pyruvate - the metabolic precursor of acetyl coA

Question 2

How does Glucose Enter the cell?

Answer 2

1) facilitated diffusion - GLUT transport proteins in the cell membrane
2) Na+ dependent co transport

Question 3

Once Glucose is in the cell, how do you prevent it from leaving again?

Answer 3

once inside, the glucose is phosphorylated, thus trapping it by conversion to glucose 6 phosphate

*there are no cell-membrane transport systems for phosphorylated sugars!!*

Question 4

What is phosphorylation catalized by?

Answer 4

Hexokinase- most cell types

glucokinase - liver parenchymal cells and pancreatic islet cells

Question 5

Difference between Glucokinase and Hexokinase?

Answer 5

Hexokinase= has a very low Vmax and a low Km, regulated allosterically

Glucokinase= has a very high Vmax and a high Km, regulated by direct inhibition

*therefore, when there are small amounts of glucose (fasting state), the hexokinase has a greater affinity- so it binds tighter to the glucose. However, when there is a large amount of glucose (fed state), use of glucokinase is prefered because you have a greater capacity when you use glucokinase

Question 6

What are the products of aerobic vs. anaerobic glycolysis?

Answer 6

aerobic - makes pyruvate

anaerobic - makes lactate

Question 7

What is the rate limiting step of glycolysis?

Answer 7

the enzyme phosphofructokinase 1

Question 8

What is substrate level phosphorylation and how does it differ from indirect phosphorylation?

Answer 8

substrate level phos= direct production of ATP

indirect phos= reduction of NADH under aerobic conditions

Question 9

Under anaerobic conditions, what is pyruvate converted to?

Answer 9

it is reduced to lactate under anaerobic conditions

Question 10

Anaerobic metabolism can lead to..

Answer 10

1) muscle cramping during vigorous exercise
2) lactic acidosis - elevated plasma levels of lactic acid secondary to circulatory collapse (MI, PE, or haemorrhage). It is potentially fatal

Question 11

What are other metabolic fates of pyruvate?

Answer 11

• under aerobic conditions - to acetyl coA, then into the TCA cycle
• serve as a precursor for Fatty acid synthesis
• convert to oxaloacetate and enter TCA cycle
• serve as precursor for gluconeogenesis
• reduce to ethanol (in microorganisms)

Question 12

How much ATP overall do we yield from glycolysis?

Answer 12

we invest 2 ATP and we make 9, therefore

7 ATP overall

Question 13

How do we regulate glycolysis?

Answer 13

1) feedback and allosteric inhibiton of enzymes

• PFK1 inhibitied allosterically by ATP
• Glucokinase inhibited by F6P

2) Hormonal regulation

• PFK1 is activated allosterically by Fructose 2,6,bisphosphate produced by PFK2.
• F2,6,B inhibitis gluconeogenesis as well
• Insulin and Glucagon control PFK2 activity and thus regulate F26B levels

Question 14

Describe the insulin/glucagon balance in fed vs. fasting state

Answer 14

Fed state, insulin produced and the glucose it absorbed quickly from the blood- increase the concentration of F2,6,B, increase the rate of glycolysis and decrease gluconeogenesis

In the Fasting state, glucagon is produced and it decreases the concentration of F2,6,B and furthermore the rate of glycolysis - while increasing the rate of gluconeogenesis

Question 15

What is hereditary myopathy with lactic acidosis?

Answer 15

autosomal recessive muscular disorder

symptoms: exercise intolerance, muscle tenderness, cramps, dyspnea, palpitations

biochemical features: lactic acidosis, rhabdomyolysis

prognosis: chronic disorder