Lipid metabolism — Flashcards

Flashcard 261: A 3 y/o girl comes with several months of fatigue and difficulty walking. -Physical examination: Decreased power in all extremities but no ataxia. -Cardiac auscultation: 1/6 systolic murmur & an S3 gallop. -Labs: Glucose 37 mg/dL Creatine kinase 304 U/L (normal XX: 10 - 70) Urinalysis: Protein, glucose, ketones, Leukocyte esterase, nitrites: all Negative -Muscle biopsy: Very low carnitine content. -Which substance has deficient synthesis in this patient's disease?

Answer: Acetoacetate (Ketone bodies) Due to Primary carnitine deficiency (impairs fatty acid transport into mitochondria) Symptoms: Cardiac & skeletal muscle cells injury, and impaired ketone body production by the liver during fasting periods.

Flashcard 262: An 18-month-old boy presents with neurologic regression. - He developed a gradual regression of developmental milestones such as inability to sit with support. - Poor head control, loss of social smile. - Physical exam: enlarged liver and spleen, hypotonia, lack of deep tendon reflexes in all limbs. - Cherry-red spot on fundoscopic exam. The patient most likely has an accumulation of which substrate?

Answer: Sphingomyelin (Due to Niemann-Pick disease, caused by deficiency of sphingomyelinase) Note: Hepatosplenomegaly is present in Niemann-Pick disease but absent in Tay-Sachs disease (which involves GM2 ganglioside accumulation).

Flashcard 263: A patient presents with hypoketotic hypoglycemia triggered by fasting. - What is the most likely enzyme deficiency? - Which substances have deficient synthesis in this patient?

Answer: 1. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency 2. Ketone bodies (e.g., acetoacetate) MCAD deficiency is the most common fatty acid oxidation disorder. It results in an inability to oxidize fatty acids into acetyl-CoA, leading to impaired ketogenesis and gluconeogenesis during fasting.

Flashcard 264: What is the status of the following in **Carnitine deficiency**? - Acetoacetate - Arachidonic acid - Glutathione - Homocysteine - Lactate - Palmitate (oxidation)

Answer: - **Acetoacetate:** Decreased (impaired ketogenesis) - **Arachidonic acid:** Unaffected - **Glutathione:** Unaffected - **Homocysteine:** Unaffected - **Lactate:** Unaffected - **Palmitate (oxidation):** Decreased (long-chain fatty acids require the carnitine shuttle)

Extra: In **carnitine deficiency**, the transport of long-chain fatty acids (LCFAs) like **palmitate** (C16) into the mitochondria is impaired. **Consequences:** 1. **Impaired β-oxidation**: LCFAs cannot enter the mitochondrial matrix. 2. **Hypoketotic hypoglycemia**: Since β-oxidation is the primary source of acetyl-CoA for ketogenesis and ATP for gluconeogenesis during fasting, levels of ketone bodies (like **acetoacetate**) and glucose fall. 3. **Other metabolites**: Arachidonic acid (membrane phospholipid component), glutathione (antioxidant), homocysteine (methionine cycle), and lactate (glycolysis) are not directly involved in the carnitine shuttle pathway and remain largely unaffected.

Flashcard 265: 35 y/o man comes with skin lesions on his palms. -Patient has yellowish skin nodules over palmar creases. -It has been increasing in size and number over the past several years. -He has small clusters of yellow papules on his elbows, knees, and buttocks. -Biopsy of skin lesion:accumulation of lipd-laden macrophages. -Lack of ApoE3 & ApoE4 in his circulation lipoproteins. -What is the most likely impaired in this patient?

Answer: Chylomicron remnant uptake by the liver cells. or VLDL remants which means he has high accumulation of the two. due to Familial dysbetalipoproteinemia (type 3). (palmar xanthomas)

Flashcard 266: Which organelle is the primary site for the initial $\beta$-oxidation of **Very Long Chain Fatty Acids (VLCFAs)**?

Answer: Peroxisomes

Extra: Very Long Chain Fatty Acids (VLCFAs, >22 carbons) cannot enter the mitochondria directly. They undergo initial $\beta$-oxidation in **peroxisomes** until they are shortened to medium or long-chain fatty acids, which are then transported to the **mitochondria** for complete oxidation. Defects in peroxisomal VLCFA oxidation lead to conditions like **Zellweger syndrome** and **X-linked adrenoleukodystrophy**.

Flashcard 267: 72 y/o woman found lying on the floor in her home for the past 2 days. - She fell and injured her right hip, was unable to get up and call for help. - She did not drink anything during that time. - Physical exam: dehydration, right hip tenderness. - Labs: serum glucose 72 mg/dL & positive urine ketones. - Radiographs: right femoral neck fracture. - Increased activity of what enzyme is most likely contributing to both the serum & urine lab findings?

Answer: Hormone-sensitive lipase In starvation, HSL breaks down adipose triglycerides into glycerol and fatty acids. - Glycerol: Substrate for gluconeogenesis (maintaining serum glucose). - Fatty acids: Substrate for ketogenesis (producing urine ketones).

Flashcard 268: What protein is responsible for the rate limiting step in steroidogenesis?_____

Answer: StAR (Steroidogenic acute regulatory protein)

Flashcard 269: Which classes of steroid hormones (2) are decreased in 17-hydroxylase deficiency?_____

Answer: glucocorticoids and androgens

Flashcard 270: What is the mode of inheritance of Niemann Pick disease?_____

Answer: Autosomal recessive