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Medical Biochemistry: Glycolysis and Regulation

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40 Questions

What is the primary function of the glycolytic pathway?

To break down glucose to provide energy and intermediates for other metabolic pathways

In which conditions can glycolysis function?

Under both aerobic and anaerobic conditions

What is the end product of glycolysis in cells with mitochondria and adequate oxygen supply?

Pyruvate

What is the consequence of deficient enzymes of glycolysis, such as pyruvate kinase?

All of the above

Why is glycolysis important for skeletal muscle function?

Both b and c

What is the primary route for carbohydrate metabolism?

Glycolysis

What is the significance of glycolysis in the absence of oxygen?

It provides ATP in the absence of oxygen

What is the role of glucokinase in the maintenance of blood glucose homeostasis?

It functions as a glucose sensor

What is the effect of elevated levels of ATP on PFK-1?

It inhibits PFK-1 activity

What is the relationship between glycolysis and other metabolic pathways?

Glycolysis is a preparatory pathway for aerobic metabolism of glucose

What is the difference between glucokinase and hexokinase in terms of glucose affinity?

Glucokinase has a lower affinity for glucose

What is the effect of fructose 6-phosphate on glucokinase activity?

It indirectly inhibits glucokinase activity

What is the role of hexokinase in the liver?

It facilitates glucose phosphorylation during hyperglycemia

What is the effect of glucose on glucokinase activity?

It indirectly stimulates glucokinase activity

What is the result of mutations that decrease the activity of glucokinase?

Maturity onset diabetes of the young type 2

What is the role of fructose 2,6-bisphosphate in the regulation of glycolysis?

It is a negative allosteric effector of Fructose 1,6-bisphosphatase

What is the primary location of transport in the epithelial cells?

Both A and B

What is the first stage of glycolysis?

Phosphorylation state

What is the net ATP production per glucose molecule metabolized in glycolysis?

2 molecules of ATP

What is the enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate?

Hexokinase

What is the characteristic of hexokinase?

High affinity for glucose

What is the function of glucokinase in β cells?

Sensing the glucose levels

What is the characteristic of glucokinase?

Present only in liver parenchymal cells and β cells

What is the result of inhibited further metabolism of glucose-6-phosphate?

Inhibition of hexokinase

What is the effect of elevated levels of glucagon and low levels of insulin during fasting?

Decrease in the rate of glycolysis

What is the role of 2,3-BPG in red blood cells?

Part of a 'shunt' reaction in glycolysis

What is the effect of fructose 1,6-bisphosphate on pyruvate kinase in the liver?

Activation

What is the effect of phosphorylation by a cAMP-dependent protein kinase on pyruvate kinase?

Inactivation

What is the effect of glucagon on pyruvate kinase?

Inactivation

What is the effect of fructose 2,6-bisphosphate on glycolysis?

Stimulation

What happens to PEP when pyruvate kinase is inactivated?

Enters the gluconeogenesis pathway

What is the effect of insulin on fructose 2,6-bisphosphate?

Increase in concentration

What is a common complication in individuals with pyruvate kinase deficiency?

Hemolytic anemia

What is the result of an elevated NADH/NAD+ ratio in exercising skeletal muscle?

Increased lactate production

In which tissues is lactate oxidized to pyruvate?

Liver and heart

What is the result of lactate accumulation in muscle during intense exercise?

Decreased intracellular pH

What is the direction of the lactate dehydrogenase reaction dependent on?

The relative intracellular concentrations of pyruvate and lactate

What is the fate of lactate in the liver?

It is oxidized in the citric acid cycle

What is lactic acidosis?

Elevated concentrations of lactate in the plasma

What can cause lactic acidosis?

Myocardial infarction

Study Notes

Major Pathways of Carbohydrate Metabolism

  • Glucose is the central molecule of carbohydrate metabolism
  • Major pathways of carbohydrate metabolism begin or end with glucose
  • These pathways include:
    • Utilization of glucose as a source of energy
    • Gluconeogenesis from non-carbohydrate precursors
    • Storage of glucose as glycogen
    • Release of glucose from glycogen
    • Pentose phosphate pathway for production of NADPH
    • Use of glucose in glucuronic acid pathway for drug detoxification

Overview of Glycolysis

  • Glycolysis is the breakdown of glucose to provide energy (in the form of ATP) and intermediates for other metabolic pathways
  • Glycolysis is the principal route for carbohydrate metabolism
  • Glycolysis provides ATP in the absence of oxygen, allowing skeletal muscle to perform at high levels of work output when oxygen supply is insufficient
  • Diseases in which enzymes of glycolysis are deficient are mainly seen as hemolytic anemias or fatigue

Stages of Glycolysis

  • Phosphorylation stage: glucose is converted to glucose-6-phosphate using ATP
  • Splitting stage: aldolase and isomerase reactions occur
  • Oxido-Reduction stage: ATP is produced by substrate-level phosphorylation

Regulation of Glycolysis

  • Hexokinase: phosphorylates glucose to glucose-6-phosphate, inhibited by glucose 6-phosphate, and has a high affinity for glucose
  • Glucokinase: phosphorylates glucose to glucose-6-phosphate in liver parenchymal cells and β cells of the pancreas, has a lower affinity for glucose, and functions as a glucose sensor
  • 6-Phosphofructo-1 kinase: a regulatory enzyme of glycolysis, inhibited by ATP and activated by fructose 2,6-bisphosphate
  • Pyruvate kinase: activated by fructose 1,6-bisphosphate, and inactivated by phosphorylation by a cAMP-dependent protein kinase

Pyruvate Kinase Deficiency

  • A rare genetic disorder that causes hemolytic anemia and associated complications
  • Symptoms may range from mild to severe, and may include an enlarged spleen, excess iron in the blood, and gallstones
  • Severe cases can be life-threatening in infancy and may require regular blood transfusions to survive

Lactate Formation in Muscle

  • In exercising skeletal muscle, NADH production exceeds the oxidative capacity of the respiratory chain, leading to an elevated NADH/NAD+ ratio and favoring the reduction of pyruvate to lactate
  • Lactate accumulates in muscle, causing a drop in intracellular pH, potentially resulting in cramps
  • Lactate can be used by the liver to make glucose

Lactic Acidosis

  • Elevated concentrations of lactate in the plasma, often occurring when there is a collapse of the circulatory system or when an individual is in shock
  • May occur in myocardial infarction, pulmonary embolism, and uncontrolled hemorrhage

Learn about the major pathways of carbohydrate metabolism, including glycolysis, gluconeogenesis, glycogen storage, and pentose phosphate pathway. Understand the regulation of glucose utilization and its various roles in the body.

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