Category 4 Flashcards
(15 cards)
Describe the role of glucokinase in the liver and how it differs from hexokinase found in most other tissues. Why is this difference metabolically significant for the liver’s function in glucose homeostasis?
Glucokinase, present in the liver and pancreas, has a high Km for glucose compared to hexokinase, which allows it to function effectively only when glucose levels are high. This enables the liver to act as a glucose buffer, converting excess glucose into glycogen without competing with other tissues for glucose during normal or low blood sugar levels.
Explain why fatty acids are considered a more efficient long-term energy storage molecule compared to glucose and glycogen. Provide two reasons based on their biochemical properties.
Fatty acids are more energy-dense as they are highly reduced, producing more ATP per carbon upon oxidation. Additionally, they are stored in an anhydrous form, whereas glycogen binds water, making fat a more compact and efficient storage form.
Outline the carnitine shuttle system. What is its primary function in fatty acid oxidation, and which key enzymes are involved in this process?
The carnitine shuttle transports long-chain fatty acyl-CoAs from the cytosol into the mitochondrial matrix for β-oxidation. It involves carnitine acyltransferase I (outer membrane), a translocase (inner membrane), and carnitine acyltransferase II (inner membrane).
Summarise the four steps of beta-oxidation (OHOT). What are the direct products of each round, and how many rounds are required for the complete oxidation of palmitoyl-CoA (C16)?
The four steps are: Oxidation (FADH₂ production), Hydration, Oxidation (NADH production), and Thiolysis (acetyl CoA release). Each round produces 1 FADH₂, 1 NADH, and 1 acetyl CoA. Palmitoyl-CoA undergoes 7 rounds to yield 8 acetyl CoA molecules.
Explain the central role of acetyl CoA in both catabolic and anabolic processes. Provide at least three distinct metabolic fates of acetyl CoA as described in the sources.
Acetyl CoA is a key metabolic intermediate that connects carbohydrate, fat, and protein metabolism. Its fates include: entering the citric acid cycle for ATP production, conversion to ketone bodies during fasting, and serving as a precursor for fatty acid and cholesterol synthesis.
Describe the process of ketogenesis and identify the primary location where it occurs. Under what physiological conditions is ketogenesis significantly upregulated?
Ketogenesis occurs in the mitochondria of liver cells, producing ketone bodies from excess acetyl CoA. It is upregulated during prolonged fasting, starvation, or uncontrolled diabetes when glucose is scarce and fatty acid oxidation is high.
What is the significance of malonyl CoA in the coordination of fatty acid synthesis and oxidation? Explain its regulatory effect on fatty acid metabolism.
Malonyl CoA is a key regulator that inhibits carnitine acyltransferase I, blocking the entry of fatty acyl-CoAs into mitochondria for β-oxidation. This prevents simultaneous synthesis and degradation of fatty acids, avoiding a futile cycle.
Outline the citrate shuttle and explain its importance in fatty acid synthesis. What are the net products transported from the mitochondria to the cytosol via this shuttle?
The citrate shuttle moves acetyl CoA from mitochondria to the cytosol by converting it to citrate, which crosses the mitochondrial membrane. In the cytosol, citrate is cleaved to regenerate acetyl CoA and oxaloacetate. NADPH is also produced, essential for fatty acid synthesis.
Explain how aspirin exerts its anti-inflammatory and analgesic effects by inhibiting prostaglandin synthesis. What specific enzyme and mechanism are involved?
Aspirin irreversibly inhibits cyclooxygenase (COX), part of prostaglandin synthase, by acetylating a serine residue in its active site. This blocks arachidonate access, preventing synthesis of prostaglandin H₂, a precursor to inflammatory mediators.
Describe the role of Low-Density Lipoproteins (LDLs) in cholesterol transport and explain how dysfunctional LDL receptors can contribute to the development of atherosclerosis.
LDLs deliver cholesterol to peripheral tissues via LDL receptor-mediated endocytosis. When LDL receptors are absent or defective, cholesterol accumulates in the blood, is taken up by macrophages, and contributes to plaque formation, leading to atherosclerosis.
Where does the oxidation of very long-chain fatty acids (longer than 20 carbons) primarily take place?
In the peroxisomes, not the mitochondria.
What is the primary role of High-Density Lipoproteins (HDLs) in lipid transport?
Transport of choolesterol in blood plasma from dying cells, returning it to the liver.
Animals cannot convert oleate to linoleate. What are linoleate and alpha-linolenate termed as in the diet due to this inability?
Essential fatty acids
Which molecule inhibits the carnitine shuttle and why is this important?
Malonyl-CoA is formed in the first step of fatty acid synthesis: it inhibits fatty acid oxidation, ensuring that oxidation and synthesis cannot occur simultaneously.
Excessive alcohol intake is discussed as leading to metabolic dysregulation. What molecule’s accumulation signals that fatty acid oxidation is not required and can lead to “fatty liver”?
High Acetyl CoA, leads to excess fatty acid synthesis.
