Lipid metabolism – II: Ketone body metabolism: Synthesis, Utilization and Significance. Cholesterol de novo synthesis. Synthesis of cholesterol derivatives. Flashcards
(25 cards)
What are the three main ketone bodies, and where are they synthesized?
Acetone, acetoacetate, and β-hydroxybutyrate. They are synthesized in the liver from acetyl CoA.
What are the consequences of ketoacidosis?
Elevated ketone bodies lower blood pH (acidosis), which can cause coma or death if severe. Blood ketone levels rise above 90 mg/100 mL (normal < 3 mg/100 mL).
How are ketone bodies used by extrahepatic tissues?
Acetoacetate and β-hydroxybutyrate are converted back to acetyl CoA and oxidized via the citric acid cycle in tissues like the brain, heart, and skeletal muscles.
Why does untreated diabetes lead to ketosis?
In diabetes, cells cannot uptake glucose efficiently, leading to increased fatty acid breakdown. Excess acetyl CoA is converted to ketone bodies, overwhelming their oxidation capacity.
What is the starting molecule for cholesterol synthesis, and where does it primarily occur?
Acetyl CoA is the precursor. Cholesterol synthesis primarily occurs in the liver.
How does LDL contribute to atherosclerosis?
Oxidized LDL accumulates in arterial walls, attracting macrophages that become foam cells, forming plaques that can obstruct blood flow or rupture.
How do statins work, and what condition do they treat?
Statins inhibit HMG CoA reductase, reducing cholesterol synthesis. They treat hypercholesterolemia but are ineffective in familial hypercholesterolemia (LDL receptor defect).
What is the role of bile acids in cholesterol metabolism?
Bile acids solubilize cholesterol in bile, preventing gallstones. Most are reabsorbed, but lost amounts are replaced by liver synthesis (~600 mg/day).
Name two classes of adrenal steroid hormones and their functions.
Mineralocorticoids (e.g., aldosterone): Regulate ion reabsorption in kidneys.
Glucocorticoids (e.g., cortisol): Regulate gluconeogenesis and inflammation
List three fates of cholesterol in the body.
Converted to bile acids (major pathway).
Precursor for steroid hormones (e.g., cortisol, estrogen).
Converted to vitamin D₃ in the skin (via 7-dehydrocholesterol).
Why can’t the liver use ketone bodies, and what critical enzyme do other tissues have that the liver lacks?
Liver lacks β-ketoacyl-CoA transferase (succinyl-CoA→acetoacetate). Extrahepatic tissues use this to convert ketones → acetyl-CoA.
What enzyme is unique to ketone body synthesis (not shared with cholesterol synthesis) and where does it occur?
HMG-CoA synthase (mitochondrial isoform) – Liver mitochondria only. (Cytosolic HMG-CoA synthase is for cholesterol.)
A diabetic patient presents with fruity breath, nausea, and Kussmaul respirations. Lab shows pH 7.1, glucose 500 mg/dL, and ketones 4+. What’s the biochemical link between hyperglycemia and ketosis?
Insulin deficiency → unchecked lipolysis → excess acetyl-CoA → ketogenesis (overwhelms citric acid cycle, diverted to ketones).
Which ketone body is volatile and excreted via lungs (fruity breath)?
Acetone (non-metabolizable; only ketone exhaled).
What’s the irreversible, regulated step in cholesterol synthesis, and what drug targets it?
HMG-CoA reductase (converts HMG-CoA → mevalonate). Statins inhibit this step.
What transforms macrophages into foam cells in plaques?
Uncontrolled uptake of oxidized LDL via scavenger receptors (not LDL receptors!).
Why are statins ineffective in homozygous familial hypercholesterolemia?
LDL receptor is nonfunctional (or absent) – statins rely on upregulating LDL receptors to clear cholesterol.
A patient with RUQ pain and steatorrhea has ultrasound showing gallstones. Why does cholesterol precipitate in bile?
Imbalance in bile acid/cholesterol ratio (bile acids normally solubilize cholesterol).
What amino acids conjugate bile acids to form bile salts, and why?
Glycine or taurine – increases solubility at intestinal pH.
What’s the common precursor for all steroid hormones, and which enzyme initiates the pathway?
Cholesterol → Pregnenolone (via P450scc/desmolase in mitochondria).
Which adrenal steroid hormone requires CYP17 (17α-hydroxylase), and which does not?
Cortisol needs CYP17 (glucocorticoid pathway); aldosterone bypasses it (mineralocorticoid pathway).
What skin molecule is converted to vitamin D₃ by UV light, and what’s its source?
7-Dehydrocholesterol (derived from cholesterol).
How does ketosis in starvation differ from diabetic ketosis?
Both cause ketosis, but starvation has low insulin + low glucose; diabetes has low insulin + high glucose.
How to remember HMG-CoA reductase’s role?
HMG = How Much Gold?” – it controls cholesterol (gold) synthesis.
