GI Lipid Metab & Membrane Lipids MCQ's

During starvation, the body undergoes a process called ketogenesis, where ketone bodies are synthesized as an alternative fuel source. The liver plays a crucial role in this process as it is responsible for the production of ketone bodies. The liver breaks down fatty acids into ketone bodies, such as acetoacetate and beta-hydroxybutyrate, which can be used by various tissues, including the brain and muscles, for energy. Therefore, the liver is the organ where ketone bodies are synthesized during starvation.

Platelet activating factor (PAF)
Hormone released from phagocytic cells binds to surface receptors
Causes platelets to aggregate and degranulate. It binds to surface receptors resulting in thrombotic and inflammatory events and anaphylactic reactions
Causes neutrophils and alveoli macrophages to produce superoxide radicals (useful for killing bacteria) (slide 18 Memb Lip-Laville)

think COX

When following the Atkins diet, the body enters a state of ketosis where it relies on fat for energy instead of carbohydrates. This leads to increased beta-oxidation, the process by which fatty acids are broken down to produce energy. As a result, there is an increase in the production of ketone bodies, which are byproducts of fat metabolism. One of the symptoms of ketosis is bad breath, known as "ketone breath." Therefore, the biochemical findings in this patient would be increased beta-oxidation with subsequent increase in ketone bodies in the plasma, explaining the symptom of bad breath.

Symptoms may include enlarged spleen and liver, liver malfunction, skeletal disorders and bone lesions that may be painful, severe neurologic complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low platelets and yellow fatty deposits on the sclera. Persons affected most seriously may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.
Gaucher's disease is a genetic disease in which lipids accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is characterized by bruising, fatigue, anemia, low platelets, and enlargement of the liver and spleen. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid glucosylceramide. When the enzyme is defective, glucosylceramide accumulates, particularly in white blood cells, most often macrophages (mononuclear leukocytes). Glucosylceramidase can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.

Diseases of carnitine shuttle
Systemic primary carnitine deficiency: SLC22A5 gene on chromosome 5q31.1, renal re-uptake transporter OCTN2 (Na+-cotransport). Frequency Faroe Islands 1 in every 500, otherwise 1 in several 10000. OMIM #212140.
Hypoketotic hypoglycemia, Reye-syndrom like episodes, lethargy, somnolence, hepato- and cardiomegaly.
Treatment: oral supplementation of carnitine
Carnitine palmitoyltransferase I deficiency: hypoketotic hypoglycemia, Reye-syndrom like episodes,
hepatomegaly, muscle weakness. OMIM #255120.
Treatment: prevent hypoglycemia with short- and medium-chain fa in diet
Carnitine-acylcarnitine translocase deficiency: Presents within hours of birth with seizures, bradycardia, breathing problems, hypoketotic hypoglycemia, hyperammonemia, hepatomegaly, cardiomyopathy, muscle weakness, sudden infant death. OMIM #212138.
Treatment: low lipid intake, medium chain fa, carnitine, avoid strenuous exercise.
Carnitine palmitoyltransferase II deficiency: Three forms:
Adult: OMIM #255110. Muscle problems (myalgia, rhabdomyolysis, myoglobinuria) during attacks, otherwise normal. Attacks induced by exercise, fasting, high-fat diet, infection. Highly variable age of onset, | more strongly affected.
Infantile: OMIM #600649. Age of onset usually _ 1a, but sometimes later. Hypoketotic hypoglycemia, loss of consciousness and seizures, hepato- and cardiomegaly.
Neonate: OMIM #608836. Onset hours to days after birth, rapidly fatal from cardiac, respiratory or liver failure.
Neuronal migration defects, kidney dysorganization. carnitine formed in liver and kidney from Lys and Met
supplementation not required in healthy individual 12 C-atoms pass membrane by diffusion
distribution of acyl-CoA between cytosol (anabolic) and mito (catabolic)
rate-limiting step of FA breakdown!
( slide 20-22 F.A metab-BUX)

When the LDL receptor (LDLR) is down-regulated, it means that there are low levels of LDL cholesterol being taken up by the cell. In this situation, the cell requires more cholesterol for its functions. HMG-CoA reductase is the enzyme responsible for the synthesis of cholesterol in the cell. Therefore, when the LDLR is down-regulated and the cell requires cholesterol, HMG-CoA reductase is activated to produce more cholesterol. This statement correctly explains the relationship between HMG-CoA reductase, LDLR, and cholesterol synthesis in the cell.

Respiratory Distress Syndrome ***Prevalent in premature infants
Due to a deficiency in synthesis of lung surfactant
The major constituents of surfactant are **dipalmitoylphosphatidylcholine**, phosphatidylglycerol, apoproteins (surfactant proteins:Sp A,B,C) and cholesterol
(slide 15 Memb Lip-Laville)

Gaucher's disease is a genetic disease in which lipids accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is characterized by bruising, fatigue, anemia, low platelets, and enlargement of the liver and spleen. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid glucosylceramide. When the enzyme is defective, glucosylceramide accumulates, particularly in white blood cells, most often macrophages (mononuclear leukocytes). Glucosylceramidase can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.
Symptoms may include enlarged spleen and liver, liver malfunction, skeletal disorders and bone lesions that may be painful, severe neurologic complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low platelets and yellow fatty deposits on the sclera. Persons affected most seriously may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.

Inhibiting the formation of mevalonate is beneficial in lowering blood cholesterol levels because mevalonate is a precursor molecule in the cholesterol biosynthesis pathway. By inhibiting its formation, the production of cholesterol is also inhibited, leading to lower blood cholesterol levels. Mevalonate is converted to HMG-CoA, which is further converted into cholesterol. Therefore, inhibiting the formation of mevalonate indirectly inhibits the formation of cholesterol.

Successful bone marrow transplantation cures the non-neurological manifestations of the disease, because it introduces a monocyte population with active beta-glucosidase.

Nieman pick = sphingomylen

Cholesterol 7 alpha-hydroxylase is the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7-alpha-hydroxycholesterol. CYP7A1 is a cytochrome P450 heme enzyme that oxidizes cholesterol using molecular oxygen.
It is downregulated by Sterol regulatory element-binding proteins (SREBP) when plasma cholesterol levels are low. It is upregulated by the nuclear receptor LXR (liver X receptor) when cholesterol (to be specific, oxysterol) levels are high.[2]
The effect of this upregulation is to increase the production of bile acids and reduce the level of cholesterol in hepatocytes.

Lipoprotein lipase is responsible for facilitating the uptake of fatty acids in tissues, including adipose tissue. When there is severely decreased insulin output after a meal, the function of adipose tissue lipoprotein lipase is impaired. As a result, there is a lack of fatty acid uptake in adipose tissue, leading to high levels of triglycerides in the plasma. This occurs because the fatty acids are not being properly utilized and stored in adipose tissue, causing them to remain in the bloodstream.

FA synthesis and b-oxidation must not occur at the same time (futile cycle)
Compartmentalization: FA synthesis in cytosol, breakdown in mitocondria
Malonyl-CoA (substrate for FA synthesis) shuts down carnitine shuttle (rate-limiting step of FA breakdown)
FA synthesis regulated at acetyl-CoA carboxylase:
citrate signals good nutrition: allosteric
insulin=dephosphorylation=activation
glucagon + adrenalin=inc cAMP =phosphorylation=
inactivation
gene expression: insulin", glucagon#
( slide 57 F.A metab-BUX)

Diseases of carnitine shuttle
Systemic primary carnitine deficiency: SLC22A5 gene on chromosome 5q31.1, renal re-uptake transporter OCTN2 (Na+-cotransport). Frequency Faroe Islands 1 in every 500, otherwise 1 in several 10000. OMIM #212140.
Hypoketotic hypoglycemia, Reye-syndrom like episodes, lethargy, somnolence, hepato- and cardiomegaly.
Treatment: oral supplementation of carnitine
Carnitine palmitoyltransferase I deficiency: hypoketotic hypoglycemia, Reye-syndrom like episodes,
hepatomegaly, muscle weakness. OMIM #255120.
Treatment: prevent hypoglycemia with short- and medium-chain fa in diet
Carnitine-acylcarnitine translocase deficiency: Presents within hours of birth with seizures, bradycardia, breathing problems, hypoketotic hypoglycemia, hyperammonemia, hepatomegaly, cardiomyopathy, muscle weakness, sudden infant death. OMIM #212138.
Treatment: low lipid intake, medium chain fa, carnitine, avoid strenuous exercise.
Carnitine palmitoyltransferase II deficiency: Three forms:
Adult: OMIM #255110. Muscle problems (myalgia, rhabdomyolysis, myoglobinuria) during attacks, otherwise normal. Attacks induced by exercise, fasting, high-fat diet, infection. Highly variable age of onset, | more strongly affected.
Infantile: OMIM #600649. Age of onset usually _ 1a, but sometimes later. Hypoketotic hypoglycemia, loss of consciousness and seizures, hepato- and cardiomegaly.
Neonate: OMIM #608836. Onset hours to days after birth, rapidly fatal from cardiac, respiratory or liver failure.
Neuronal migration defects, kidney dysorganization. carnitine formed in liver and kidney from Lys and Met
supplementation not required in healthy individual 12 C-atoms pass membrane by diffusion
distribution of acyl-CoA between cytosol (anabolic) and mito (catabolic)
rate-limiting step of FA breakdown! ( slide 20-22 F.A metab-BUX)

Platelet activating factor (PAF)
Hormone released from phagocytic cells binds to surface receptors
Causes platelets to aggregate and degranulate. It binds to surface receptors resulting in thrombotic and inflammatory events and anaphylactic reactions
Causes neutrophils and alveoli macrophages to produce superoxide radicals (useful for killing bacteria) (slide 18 Memb Lip-Laville)

When excess acetyl-CoA cannot be utilized by the TCA cycle, it is converted into p-hydroxybutarate. This conversion occurs in the liver and is part of a metabolic pathway known as ketogenesis. p-hydroxybutarate is one of the ketone bodies produced during this process. Ketone bodies can be used as an alternative fuel source by various tissues, including the brain, when glucose availability is limited. Therefore, when excess acetyl-CoA accumulates, it is converted into p-hydroxybutarate to be used as an energy source.

The patient most likely has Krabbes disease based on the symptoms described. Krabbes disease is a rare genetic disorder that affects the nervous system. It is characterized by the loss of myelin, the protective covering of nerve cells, which leads to problems with hearing and vision, muscle weakness, and delayed development. The symptoms mentioned in the question, such as walking into objects, not responding to sounds, muscle weakness, and slow mental and motor development, align with the characteristic features of Krabbes disease.

Cardiolipin: Found in abundance in the inner mitochondrial membrane where it maintains certain respiratory complexes on the electron transport chain
The only human glycerophospholipid that is antigenic. It is recognized by antibodies raised against Trepanoma Pallidum. = Autoimmune diseases.
(slide 13 Memb Lip-Laville)

Cardiolipin from a cow heart is used as an antigen in the Wassermann test for syphilis. Anti-cardiolipin antibodies can also be increased in numerous other conditions, including systemic lupus erythematosus, malaria and tuberculosis, so this test is not specific. (wikipedia)

During the conversion of glucose-6-phosphate to ribulose-5-phosphate in the pentose phosphate pathway, NADPH is produced. NADPH is a reducing equivalent and is required for fatty acid synthesis. Therefore, this conversion provides the necessary reducing equivalents for fatty acid synthesis.

Apo Al is an important activator of lecithin cholesterol acyl transferase (LCAT).

The signs and symptoms of riboflavin deficiency typically include sore throat with redness and swelling of the mouth and throat mucosa, cheilosis and angular stomatitis (cracking of the lips and corners of the mouth), glossitis (magenta tongue with atrophy), seborrheic dermatitis or pseudo-syphilis (moist, scaly skin particularly affecting the scrotum or labia majora and the nasolabial folds), and a decreased red blood cell count with normal cell size and hemoglobin content (normochromic normocytic anemia).

Persons with chronic alcoholism can have impaired absorption of riboflavin and other vitamins such as thiamine (see Wernicke's encephalopathy).

USMLE step 1 book indicates that corneal vascularization is also a presentation for B2 deficiency.

Cytidine nucleotides are involved in phospholipid synthesis because they play a role in the activation of choline, ethanolamine, and diacylglycerol (DAG). These molecules are important components in the synthesis of phospholipids, which are essential for building cell membranes. By activating choline, ethanolamine, and DAG, cytidine nucleotides contribute to the production of phospholipids, ensuring the proper structure and function of cell membranes.

Prostaglandins are synthesized from linolenic acid, an essential fatty acid. Linolenic acid is converted into other fatty acids, such as arachidonic acid, which then serve as precursors for prostaglandin synthesis. Prostaglandins are important signaling molecules that play a role in various physiological processes, including inflammation, blood clotting, and smooth muscle contraction.