Metabolic Disorders and Pathways

Metabolic Disorders and Pathways

• Lactic Acidemia & α-ketoglutarate Dehydrogenase Deficiency: A reduced activity of α-ketoglutarate dehydrogenase, coupled with lactic acidemia, points to a mutation in the E2 subunit of pyruvate dehydrogenase.

Thiamine Deficiency & Metabolic Acidosis

• Metabolic Acidosis in Thiamine Deficiency: A thiamine deficiency leads to the accumulation of pyruvic acid.

Succinate Dehydrogenase in the TCA Cycle

• Unique Characteristic of Succinate Dehydrogenase: The only TCA cycle enzyme embedded in the inner mitochondrial membrane is succinate dehydrogenase.

TCA Cycle Stimulation During Exercise

• Stimulation of the TCA Cycle During Exercise: Stimulation of the TCA cycle during exercise is primarily driven by a decreased NADH/NAD+ ratio, which stimulates the flux through various enzymes.

Coenzyme A Deficiency

• Pantothenate Deficiency: A pantothenate deficiency impedes coenzyme A synthesis.

Electron Donors in the TCA Cycle

• Electron Donor for TCA Cycle Reduced Cofactors: Acetyl-CoA donates eight electrons to cofactors for ATP production in oxidative phosphorylation.

Hypoxia and Cardiomyocytes

• Hypoxic Effects on Cardiomyocytes: During hypoxia, the TCA cycle is impaired, pyruvate oxidation decreases, and lactate becomes a fuel source, causing citrate accumulation.

Fatty Acid Metabolism in Mitochondria

• Acetyl-CoA Metabolism in Mitochondria: One molecule of acetyl-CoA produces two molecules of CO2, three molecules of NADH, one FAD(2H) and no ATP during oxidation in the mitochondrial TCA cycle.

Neonatal Acidosis and PDC α-subunit Mutation

• Consequences of PDC α-subunit Mutation: An X-linked dominant mutation in the PDC α-subunit results in increased plasma concentrations of lactate and pyruvate.

Pyruvate Carboxylase Deficiency and Lactic Acidemia

• Mechanism of Lactic Acidemia in Pyruvate Carboxylase Deficiency: Pyruvate carboxylase deficiency leads to lactic acidemia due to an accumulation of acetyl-CoA in the mitochondria.

Electron Transport Chain Oxidation States

• Electron Transport Chain Components in Oxidized State: After 7 minutes of cyanide addition in a malate experiment, complex I of the electron transport chain would be oxidized.

Valinomycin and Proton Motive Force

• Valinomycin Effect on Proton Motive Force: Valinomycin increases potassium ion permeability across the inner mitochondrial membrane, decreasing the proton motive force to zero.

Dinitrophenol and Oxidative Phosphorylation

• Mechanism of Dinitrophenol (Uncoupler): Dinitrophenol uncouples oxidative phosphorylation by allowing proton exchange across the inner mitochondrial membrane.

Iron-Deficiency Anemia and Fatigue

• Iron Deficiency and Fatigue: Iron is a cofactor for α-ketoglutarate dehydrogenase in the TCA cycle, and its deficiency impairs electron flow within the electron transport chain, leading to fatigue.

OXPHOS Disease Characteristics

• OXPHOS Disease Indicators: OXPHOS disease patients display a high NADH:NAD + ratio in the mitochondria.

Lead Exposure and Heme Synthesis

• Lead Exposure and Protein/Complex Function: Lead exposure, interfering with heme synthesis, has minimal effect on myoglobin function.

Rotenone Inhibition and ATP Production

• Rotenone Effect on ATP Production: Rotenone, which inhibits NADH dehydrogenase, severely reduces ATP production by inhibiting electron flow.

Mitochondrial Component Disruption

• Mitochondrial Component Loss: Disrupting noncovalent interactions in mitochondria disrupts complex I of the electron transport chain, resulting in minimal oxygen consumption.

UCPs and Weight Loss

• UCP Activation and Potential Side Effect: Activating UCPs, to facilitate weight loss, could lead to increased body temperature as a side effect.

Free Radical Damage and Antioxidants

• Vitamin Protects From Free Radical Damage: Vitamin E and Glutathione peroxidase, Superoxide dismutase and beta-carotene can protect from free radical damage to help neutralize and stabilize free radicals.

Superoxide Dismutase Reaction

• Superoxide Dismutase Reaction: Superoxide dismutase catalyzes the conversion of two superoxide radicals to hydrogen peroxide and oxygen.

Mechanism of Vitamin E as an Antioxidant

• Vitamin E Antioxidant Mechanism: Vitamin E reduces free radicals, participating in their reduction.

Hydrogen Peroxide and Metal Catalysts

• Metal Catalysts for Hydrogen Peroxide: An accumulation of hydrogen peroxide can be converted into more dangerous radical forms in the presence of iron.

Mitochondrial DNA Oxidative Damage

• Mitochondrial DNA vs. Nuclear DNA Oxidative Damage: Mitochondrial DNA is substantially more susceptible to oxidative damage than nuclear DNA due in part to a permeable mitochondrial membrane and lack of histone protection.

Chronic Granulomatous Disease and Reactive Oxygen Species

• Chronic Granulomatous Disease Defect: Patients with CGD primarily have a defect in producing hypochlorous acid, a reactive oxygen species.

Amyotrophic Lateral Sclerosis and Detoxification

• Amyotrophic Lateral Sclerosis and Detoxification Defect: Amyotrophic lateral sclerosis mutations lead to an inability to detoxify superoxides.

Nitroglycerin, NO and Reactive Nitrogen-Oxygen Species

• Nitroglycerin/NO and Disease: High concentrations of nitric oxide can produce reactive nitrogen-oxygen species implicated in diseases like rheumatoid arthritis.

Xenobiotics and Free Radical Injury

• Xenobiotics and the Production of Free Radicals: Xenobiotics can induce enzymes like cytochrome P450, which contribute to oxidative stress and free radical production in the body.

Antioxidant-Rich Foods

• Antioxidant-Rich Food Source: Citrus fruits notably contain antioxidants.

Glucagon, Glycogen Degradation and Products

• Glucagon and Glycogen Degradation: Glucagon stimulates glycogen degradation, producing more glucose 1-phosphate than free glucose in the liver.

Glycogen Storage Diseases

• Glycogen Storage Disease Properties: Glycogen storage diseases, except type O, primarily affect the liver, causing hepatomegaly, and frequently lead to hypoglycemia.

Neonatal Hypoglycemia

• Neonatal Glucose Levels: Normal physiological changes, not necessarily a disease or intervention such as IV dextrose, can explain the 50 to 80 mg/dL glucose levels seen at 1 and 2 hours post-delivery.

Muscle Phosphorylase Deficiency and Exercise

• Muscle Phosphorylase Deficiency Symptoms: Patients with muscle phosphorylase deficiency will show symptoms of decreased lactate levels, lower exercise tolerance and higher levels of glycogen in biopsies taken from the muscle tissues

Glucose Tolerance Test and Glycogen Metabolism

• Glucose Tolerance Test and Liver Enzyme Activity: Normal glucose tolerance results in enhanced liver glycogen synthase activity and a decreased ratio of glycogen phosphorylase a to glycogen phosphorylase b .

Diabetes, Glycogen Metabolism and Hepatic Enzymes

• Diabetes, Hepatic Enzymes and Glycogen Metabolism: In type 1 diabetes with insufficient insulin and little food, liver glycogen degradation enzymes are highly active.

Muscle Protein Kinase A Mutation and Glycogen Degradation

• Muscle Protein Kinase A Mutation and Glycogen Degradation: A dysfunctional protein kinase A that cannot respond to high cAMP levels means glycogen degradation in the muscle would not be significantly affected.

Maintaining Blood Glucose

• Maintaining Blood Glucose Levels: Liver glucose 6-phosphatase is needed to maintain blood glucose levels.

Glycogen Synthesis and Degradation

• Differences Between Glycogen Synthesis and Degradation: Glycogen synthesis and degradation utilize distinct enzymes; synthesis requires ATP for glucose activation.

Explore key concepts related to metabolic disorders, including lactic acidemia and thiamine deficiency. This quiz covers important pathways like the TCA cycle and the role of coenzyme A. Test your knowledge on enzyme functions and their implications in metabolic health.