seminar week 4: q Flashcards
- Describe importance of AMP on glucose metabolism
- AMP can directly influence enzymes involved in glycolysis and gluconeogenesis. For instance, during times of energy demand (when AMP levels are high), enzymes like phosphofructokinase-1 (PFK-1) in glycolysis are activated, promoting the breakdown of glucose to generate ATP. Conversely, gluconeogenesis, which synthesizes glucose, is inhibited under high AMP conditions to conserve energy.
- Describe importance of reduction of pyruvate to lactate
Regeneration of NAD+: During glycolysis, glucose is converted to pyruvate, producing NADH. In the absence of sufficient oxygen (anaerobic conditions), the conversion of pyruvate to lactate by the enzyme lactate dehydrogenase helps regenerate NAD+ from NADH. This regeneration of NAD+ is crucial for sustaining glycolysis because it allows the continued production of ATP through glycolytic reactions. Without sufficient NAD+, glycolysis would halt due to a lack of available electron carriers (NAD+) to continue the process
- Describe importance of determination of lactate in plasma
Overall, determining lactate levels in plasma provides valuable information regarding tissue oxygenation, organ function, disease severity, and the body’s response to various physiological and pathological conditions, aiding clinicians in diagnosis, monitoring, and treatment decisions.
Indicator of Tissue Hypoxia: Elevated lactate levels often indicate tissue hypoxia, where tissues are deprived of adequate oxygen. When oxygen supply is insufficient to meet cellular energy demands, anaerobic metabolism increases, leading to the production of lactate. Monitoring lactate levels helps clinicians assess tissue oxygenation and the severity of conditions such as shock, sepsis, or other critical illnesses.
Diagnostic Marker: Lactate measurements aid in diagnosing various medical conditions. Persistently high lactate levels can indicate conditions such as sepsis, severe infections, heart failure, liver disease, certain cancers, or mitochondrial disorders.
Prognostic Indicator: In critical care settings, elevated lactate levels can serve as a prognostic marker for patient outcomes. Higher lactate concentrations upon admission or during treatment in intensive care units (ICUs) can indicate increased mortality risk or predict the severity of the patient’s condition.
Monitoring Treatment Response: Serial lactate measurements help clinicians monitor the response to treatment in critically ill patients. A decrease in lactate levels over time can indicate an improvement in tissue oxygenation and the patient’s response to therapy.
Exercise Physiology: Lactate levels can also be assessed in exercise physiology. During intense physical activity, the accumulation of lactate serves as an indicator of the transition from aerobic to anaerobic metabolism. Monitoring lactate levels helps assess an individual’s exercise tolerance and fitness level.
Guiding Resuscitation: In emergency medicine and trauma care, measuring lactate levels assists in guiding resuscitation efforts. It helps in making rapid decisions regarding fluid resuscitation, oxygenation, and overall management of critically ill patients.
- Describe importance of cAMP on glucose metabolism
Cyclic adenosine monophosphate (cAMP) plays a crucial role in regulating glucose metabolism by acting as a secondary messenger in various signaling pathways
Control of Gluconeogenesis and Glycolysis:. It stimulates gluconeogenesis by promoting the expression and activation of key enzymes like phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase. Additionally, cAMP can inhibit glycolysis indirectly by suppressing the activity of phosphofructokinase-1 (PFK-1), a key enzyme in glycolysis, via the PKA-mediated phosphorylation of regulatory enzymes.
- Describe importance of glyceraldehyde 3-phosphate
- G3P is an intermediate in the glycolytic pathway, specifically in the second half of glycolysis. It is formed from the breakdown of glucose-6-phosphate and further converted to 1,3-bisphosphoglycerate by the enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). This conversion step is crucial for generating high-energy carriers such as NADH, which subsequently contribute to the production of ATP in the later steps of glycolysis. G3P serves as a pivotal point in the conversion of glucose to pyruvate, facilitating ATP generation and the production of reducing equivalents.
In gluconeogenesis, G3P serves as a substrate for the reverse reaction of glycolysis. It can be converted into glucose-6-phosphate, playing a crucial role in the synthesis of glucose from non-carbohydrate precursors such as lactate, amino acids, and glycerol. This process is essential for maintaining blood glucose levels during fasting or periods of low carbohydrate intake.
- Describe possibe reasons for high concentration of lactate in plasma
Intense Exercise or Physical Exertion: During vigorous exercise, muscles may require energy faster than oxygen can be delivered, leading to temporary oxygen deficiency (hypoxia) in the muscle cells. This prompts the conversion of pyruvate to lactate via anaerobic glycolysis, causing a transient increase in lactate levels. This elevation in lactate often normalizes after the exercise is completed.
- ypoperfusion or Shock: Conditions that reduce blood flow or impair tissue perfusion, such as septic shock or other circulatory problems, can lead to insufficient oxygen delivery to tissues (tissue hypoxia). In response, cells switch to anaerobic metabolism, generating lactate as a byproduct. Elevated lactate levels in such cases can indicate tissue hypoxia and the severity of the underlying condition.
- Sepsis or Infections: Severe infections, particularly in cases of sepsis, can cause systemic inflammation and impair tissue oxygenation, leading to an increased production of lactate due to cellular hypoxia and altered metabolism.
Liver Dysfunction: The liver plays a crucial role in lactate metabolism by clearing lactate from the bloodstream. Liver diseases or conditions affecting liver function, such as liver failure or impaired blood flow to the liver, can result in reduced lactate clearance, leading to elevated levels of lactate in the blood.
- Describe Cori cycle.
The Cori cycle, also known as the lactic acid cycle, is a metabolic pathway that describes the interconversion of glucose and lactate between tissues, particularly between muscle and liver. It plays a crucial role in maintaining blood glucose levels and recycling lactate produced by muscles during anaerobic glycolysis.
The Cori cycle allows for the conversion of lactate produced in muscles under conditions of high energy demand or oxygen shortage (anaerobic conditions) back into glucose in the liver. This glucose can then be released into the bloodstream to supply energy to other tissues, including muscles, where it can be utilized during subsequent physical activity. The cycle helps in the maintenance of blood glucose levels and contributes to the efficient utilization of lactate as an energy source, preventing the buildup of excess lactate in the body.
- Compare anaerobic and aerobic glycolysis and indicate the end product and energy yield
Anaerobic Glycolysis:
1. Pathway: Anaerobic glycolysis occurs in the cytoplasm of cells.
2. Oxygen Requirement: Does not require oxygen.
3. End Product: Pyruvate is converted to lactate (or in some microorganisms, ethanol and carbon dioxide) in the absence of oxygen.
4. Energy Yield: Produces a net gain of 2 ATP molecules per glucose molecule.
5. NADH Production: Generates NADH during glycolysis, which is oxidized back to NAD+ by reducing pyruvate to lactate, allowing glycolysis to continue.
Aerobic Glycolysis:
1. Pathway: Aerobic glycolysis begins in the cytoplasm but continues in the mitochondria.
2. Oxygen Requirement: Requires oxygen for the continuation of the process.
3. End Product: Pyruvate is transported into the mitochondria, where it is converted to acetyl-CoA, entering the citric acid cycle (Krebs cycle). The end products of aerobic glycolysis are carbon dioxide (CO2) and water (H2O).
4. Energy Yield: Generates a net gain of 36 to 38 ATP molecules per glucose molecule. This includes ATP produced during glycolysis (2 ATP), the citric acid cycle, and oxidative phosphorylation in the electron transport chain.
5. NADH Production: NADH generated during glycolysis and the citric acid cycle is used in oxidative phosphorylation to produce ATP.
Summary:
* Anaerobic glycolysis is a faster but less efficient process, producing energy (in the form of ATP) without oxygen by converting glucose to pyruvate and then to lactate or other end products.
* Aerobic glycolysis is a more efficient process that occurs in the presence of oxygen. It involves the conversion of glucose to pyruvate, which enters the mitochondria to generate significantly more ATP through the citric acid cycle and oxidative phosphorylation.
* Anaerobic glycolysis produces a smaller amount of ATP (2 ATP per glucose) and lactate or other end products, while aerobic glycolysis generates a larger amount of ATP (36 to 38 ATP per glucose) and produces carbon dioxide and water as end products.
What are physiological and pathological causes when glucose concentration is 2,0 mmol/L?
The normal glucose concentration in the blood is 3-5 mmol/L, therefore; this is hypoglycemia.
The causes of hypoglycemia: strenuous exercise, alcohol poisoning, hyperinsulinism, diabetes mellitus, renal insufficiency/failure, hepatic cirrhosis/failure, other endocrine diseases.
ow is the metabolic pathway activated during prolonged fasting – regarding the brain. Name at least three different substrates of the metabolic pathway
The brain depends on glucose as its main fuel and will use glucose when there are adequate levels of it. During the first days of fasting the brain continues to use glucose as a fuel. In prolonged fasting, about 2-3 weeks, there are elevated levels of plasma ketone bodies, therefore they replace glucose as the primary fuel for the brain.
Three different substrates of the metabolic pathway: lactate, a-keto acids (obtained from the deamination of glycogenic amino acids) and glycerol.
Explain direct and indirect inhibition of 6-phosphofructokinase-1
Direct inhibition: Cytoplasmic citrate levels increase, this leads to direct inhibition of PFK-1 activity at the citrate regulatory site and accumulation of glucose 6-phosphate. We believe that ATP is a direct inhibitor of the phosphofructokinase-1 as well; high levels of ATP will allosterically inhibit the enzyme in the liver and lower its affinity to fructose 6-phosphate.
Indirect inhibition: When glucagon is present during fasting, it triggers a series of events that indirectly inhibits 6-phosphofructokinase-1. Glucagon increases the formation of cAMP, which activates protein kinase A. This protein kinase A adds a phosphate group to certain enzymes: phosphatase and kinase.
As a result, the activated phosphatase converts fructose 2,6-biphosphate back into fructose 6-phosphate. This causes a decrease in the concentration of fructose 2,6-biphosphate and an increase in fructose 6-phosphate. With lower levels of fructose 2,6-biphosphate, the activity of phosphofructokinase-1 decreases.
In summary, the presence of glucagon during fasting leads to a decrease in fructose 2,6-biphosphate levels, which indirectly decreases the activity of phosphofructokinase-1.
Where does the glycolysis occur – tissue(s) and organelle(s)
Aerobic glycolysis: Occurs in cells with mitochondria and adequate supply of O2
Anaerobic glycolysis: Occurs in cells which lack mitochondria erythrocytes, leukocytes, kidney medulla, testes, eye lens and skin, and cells with lack of O2
Glycolysis occurs in the cytosol (cytoplasm) in the cells.
Describe, how insulin and glucagon regulates the process of gluconeogenesis in the body:
Glucagon is secreted in response to low blood glucose, and it enhances the synthesis of PEP-carboxylase. Via cAMP and Protein Kinase A it inhibits glycolysis and increases rate of gluconeogenesis. It decreases the intracellular concentration of hepatic fructose 2,6-bisphosphate.
Insulin is secreted in response to high blood glucose, it induces the synthesis of key enzymes in the glycolysis: glucokinase, phosphofructokinase-1 and pyruvate kinase. Insulin also causes an increase in the concentration of fructose 2,6-bisphosphate. Insulin decreases the rate of gluconeogenesis.
Explain the role of phosphofructokinase 2 in gluconeogenesis
Phosphofructokinase-2 has a kinase activity that produces fructose 2,6-bisphosphate and a phosphatase activity that converts fructose 2,6-bisphosphatase back to fructose 6-phosphate. Fructose 2,6-bisphosphate is an inhibitor of fructose 1,6-bisphosphatase which is an enzyme of gluconeogenesis. The reciprocal action of fructose 2,6-bisphosphate in gluconeogenesis is inhibition.
Indicate the main function of gluconeogenesis and name at least 2 regulatory hormones:
luconeogenesis is the generation of glucose from non-carbohydrate precursors (like glycerol, lactate and amino acids for example).
The reason why we have this process is because some organs and tissues can only use glucose as their energy source. These include the brain (although ketone bodies can be used here as well), erythrocytes, testes and the kidney medulla. Usually the glucose for the supply of these tissues comes directly from carbohydrates in food or storage carbohydrates as glycogen or starch, but when these are not available, the body has another way to get around this problem and to avoid the starvation of these tissues gluconeogenesis.
Two regulatory hormones are: Glucagon (stimulates gluconeogenesis) and insulin (lowers the rate of gluconeogenesis)
