Insulin binds to what type of receptor to activate protein phosphatase, which goes on to inactivate glycogen phosphorylase kinase and glycogen phosphorylase?
An activated glycogen phosphorylase will begin what process?
During glycogen metabolism, glucose-1-phosphate is converted to UDP-glucose by which enzyme?
UDP-glucose pyrophosphorylase; UDP-glucose is the substrate for glycogen synthase
During glucose metabolism, UDP-glucose is converted to the storage form of glycogen by which enzyme?
In which organ does glycogen undergo rapid glycogenolysis during exercise?
In which organ does glycogen undergo glycogenolysis to maintain blood sugar within an appropriate range?
What type of bond is found at glycogen branch points?
What type of bond is found at side-by-side linkages of glucose in glycogen?
What enzyme creates a new branch point when assembling glycogen molecules?
What enzyme digests glycogen to create a limit dextran?
Once a limit dextran has been created, what enzyme is necessary for further digestion of the glycogen molecule?
Glycogen digestion in the lysosome occurs through which enzyme?
What molecules are the end products of glycogenolysis?
Glucose and Pi
What conversion must occur for the glucose-1-phosphate produced during glycogenolysis to be converted to glucose?
The phosphate group has to be moved from the 1 carbon to the 6 carbon
Which enzyme reacts with a limit dextran (four glucose residues in branched configuration) during degradation of glycogen to form glucose?
Which enzyme is responsible for the conversion of glucose-1-phosphate to glucose-6-phosphate?
Which enzyme degrades glycogen to glucose in the lysosome?
Lysosomal acid maltase (-1,4-glucosidase)
Glycogen storage diseases involve an abnormal accumulation of toxic levels of what substance within cells?
How many types of glycogen storage diseases are there?
Twelve glycogen metabolism enzyme deficiencies have been described in humans
What is another name for glycogen storage disease type I?
von Gierke's disease
A patient has severe fasting hypoglycemia, increased stores of glycogen in the liver, hepatomegaly, and elevated levels of lactate in his blood. What is the likely underlying metabolic deficiency?
von Gierke's disease (glycogen storage disease type I) resulting from glucose-6-phosphatase deficiency
Glycogen storage disease type I results from a deficiency of what enzyme?
What is the prognosis for a child diagnosed with Pompe disease?
Name four glycogen storage diseases.
Von Gierke's disease (type I), Pompe;s disease (type II), Cori's disease (type III), McArdle;s disease (type V) (remember: Very Poor Carbohydrate Metabolism)
How can you differentiate between a patient with Cori's disease and one with von Gierke's disease using blood samples?
Patients with Cori's disease have normal blood lactate levels due to intact gluconeogenesis, whereas those with von Gierke's have elevated blood lactate
What is another name for glycogen storage disease type II?
In a patient with McArdle's disease, would you expect increased or decreased levels of glycogen on muscle biopsy?
Increased levels of glycogen, because the muscle cannot break it down
What is another name for -1,4-glucosidase?
What disease is the result of a deficiency of lysosomal -1,4-glucosidase?
Pompe;s disease (glycogen storage disease type II)
Pompe;s disease (glycogen storage disease type II) is associated with the enlargement of what organ?
The heart (remember: Pompe's trashes the Pump)
Name three organs affected in Pompe's disease.
Heart, liver, muscle
What is another name for glycogen storage disease type III?
What is another name for -1,6-glucosidase?
What disease is the result of a deficiency of -1,6-glucosidase?
Cori's disease (glycogen storage disease type III)
What is another name for glycogen storage disease type V?
What disease is the result of a deficiency of skeletal muscle glycogen phosphorylase?
McArdle's disease (glycogen storage disease type V)
A patient has painful cramping and myoglobinuria associated with strenuous exercise. What is the likely underlying metabolic deficiency?
McArdle's disease (glycogen storage disease type V) (remember: McArdle's = Muscle)
What bodily fluid can be used to diagnose McArdle's in a patient with severe muscle cramping after exercise?
A urinalysis will show myoglobinuria
What enzyme deficiency is seen in Fabry's disease?
A patient presents with progressive neurodegeneration, hepatosplenomegaly, and a cherry-red spot on his macula. Histologic examination reveals cells containing lipid droplets, confirming a lysosomal storage disease. What are these cells called?
Foam cells; seen in Niemann-Pick disease
A patient presents with peripheral neuropathy, developmental delay, and optic atrophy. Histologic examination reveals multinucleated macrophages, confirming your diagnosis of a lysosomal storage disease. What are these cells called?
Globoid cells; seen in Krabbe's disease
A deficiency of the enzyme -galactosidase A leads to what disease?
What substrate is accumulated in Fabry's disease?
What type of inheritance does Fabry's disease demonstrate?
What is the appearance of the cells that may serve as histologic confirmation of Gaucher's disease?
Gaucher's cells are macrophages that look like crumpled tissue paper
Name two mucopolysaccharidoses.
Hunter's syndrome and Hurler's syndrome
A patient shows milder symptoms and appearance similar to Hurler's syndrome but no corneal clouding; what kind of behavior patterns do you expect?
Aggressive behavior; this describes Hunter's syndrome, an X-linked mucopolysaccharidosis
A patient has peripheral neuropathy of the hands and feet, angiokeratomas of the skin, and both cardiovascular and renal disease. These characteristics are typical of which lysosomal storage disease?
What substrate accumulates in a patient with a deficiency of -glucocerebrosidase?
Glucocerebroside; it accumulates in liver, spleen, and bone in Gaucher's disease
Name six types of sphingolipidosis.
Fabry's disease, Gaucher's disease, Niemann-Pick disease, Tay-Sachs disease, Krabbe's disease, metachromatic leukodystrophy
What substrate is accumulated in Niemann-Pick disease?
Sphingomyelin (remember: No man picks [Niemann-Pick] his nose with his sphinger [sphingomyelinase])
What enzyme deficiency leads to Gaucher's disease?
A child has progressive neurodegeneration, developmental delay, cherry-red spots on the macula, and lysosomes with onion skinning; he does not have hepatomegaly. These characteristics are typical of which lysosomal storage disease?
What is the most common lysosomal storage disorder?
A patient has developmental delay, gargoylism, airway narrowing, and corneal clouding. These characteristics are typical of which lysosomal storage disease?
Which three lysosomal storage disorders are Ashkenazi Jews at increased risk for?
Tay-Sachs, Niemann-Pick, and some forms of Gaucher's disease
What type of inheritance does Gaucher's disease demonstrate?
A patient has hepatosplenomegaly, aseptic necrosis of the femur, and abnormal macrophages on histologic examination. These characteristics are typical of which lysosomal storage disease?
What is the term for macrophages that look like crumpled tissue paper under the microscope and are associated with a lysosomal storage disease?
What enzyme deficiency leads to Niemann-Pick disease?
A deficiency of the enzyme sphingomyelinase leads to what disease?
What type of inheritance does Niemann-Pick disease demonstrate?
A child has progressive neurodegeneration, hepatosplenomegaly, and a cherry-red spot on his macula. These characteristics are typical of which lysosomal storage disease?
What enzyme deficiency leads to Tay-Sachs disease?
Hexosaminidase A (remember: Tay-SaX lacks heXosaminidase)
What substrate is accumulated in Tay-Sachs disease?
What type of inheritance does Tay-Sachs disease demonstrate?
Name two lysosomal storage diseases that may present with a cherry-red spot on the macula.
Niemann-Pick disease and Tay-Sachs disease
What enzyme deficiency leads to Krabbe's disease?
What substrate is accumulated in Krabbe's disease?
What type of inheritance does Krabbe's disease demonstrate?
A patient has peripheral neuropathy, developmental delay, and optic atrophy. These characteristics are typical of which lysosomal storage disease?
What enzyme deficiency leads to metachromatic leukodystrophy?
What substrate is accumulated in metachromatic leukodystrophy?
What type of inheritance does metachromatic leukodystrophy demonstrate?
A patient has central and peripheral demyelination with ataxia and dementia. These characteristics are typical of which lysosomal storage disease?
What enzyme deficiency leads to Hurler's syndrome?
What substrates accumulates in Hurler's syndrome?
Heparan sulfate and dermatan sulfate
What pattern of inheritance does Hurler's syndrome demonstrate?
What enzyme deficiency leads to Hunter's syndrome?
What substrates are accumulated in Hunter's syndrome?
Heparan sulfate and dermatan sulfate
What pattern of inheritance does Hunter's syndrome demonstrate?
A patient has mild developmental delay, gargoylism, and airway obstruction but no corneal clouding. These characteristics are typical of which lysosomal storage disease?
Name the two lysosomal storage diseases that lead to an accumulation of heparan sulfate and dermatan sulfate.
Hunter's syndrome and Hurler's syndrome
Name the two lysosomal storage diseases that show x-linked recessive inheritance.
Fabry's disease and Hunter's syndrome
What is the name of the shuttle that moves acetyl coenzyme A from the mitochondria to the cytoplasm to participate in fatty acid synthesis?
Citrate shuttle (remember: SYtrate = SYnthesis)
The addition of carbon dioxide to acetyl coenzyme A during fatty acid synthesis yields what molecule?
Malonyl coenzyme A
In acyl-CoA dehydrogenase deficiency, dicarboxylic acid levels _____ (increase/decrease) and glucose and ketone levels _____ (increase/decrease).
A deficiency of which enzyme in fatty acid metabolism causes an increase in dicarboxylic acids and a decrease in glucose and ketones?
Acyl-CoA dehydrogenase deficiency
What cofactor is required for the conversion of acetyl-CoA to malonyl-CoA during fatty acid synthesis?
Biotin; it donates the CO2 group
Where does fatty acid degradation occur? Where are the products of degradation consumed?
Both occur in the mitochondrion
What is the name of the shuttle that moves long-chain fatty acids from the cytoplasm to the mitochondria to participate in fatty acid degradation?
Carnitine shuttle (remember: CARnitine = CARnage of fatty acids)
After breakdown of fatty acids, the resulting acetyl-CoA groups can be put to which uses?
Ketogenesis or citric acid cycle
In which direction does the citrate shuttle move acetyl-CoA across the mitochondrial membrane?
From the mitochondria to the cytoplasm
In which direction does the carnitine shuttle move fatty acids across the mitochondrial membrane?
From the cytoplasm to the mitochondria
A deficiency of what substance will result in hypoketotic hypoglycemia?
What are the clinical sequelae of carnitine deficiency?
Weakness, hypotonia, and hypoketotic hypoglycemia due to toxic accumulation of long-chain fatty acids
Name two ketone bodies derived from acetyl-CoA. (These are found in individuals who have experienced prolonged starvation and diabetic ketoacidosis.)
Acetoacetate and -hydroxybutyrate
In a patient with high levels of circulating ketone bodies, what does the breath smell like?
Acetone (a fruity odor)
Which two precursors can be made into ketone bodies?
Amino acids and fatty acids
What is the precursor molecule to acetoacetate?
HMG coenzyme A
In alcoholism, the citric acid cycle is stalled due to excess NADH, causing a shunting of glucose and free fatty acids toward formation of _______ _______.
Which two organs can use ketone bodies as fuel during starvation?
Muscle and brain
Which ketone body cannot be detected by a urine test?
A patient with a history of alcoholism presents to the emergency department intoxicated. Excess NADH and the shunting of oxaloacetate to malate may result in finding what substance in his urine?
Where in the body are ketones synthesized?
In which two pathological states will the body produce large amounts of ketones?
Starvation and ketoacidosis
The brain can convert one ketone body into two of what type of molecule?
Acetyl-CoA for use in the tricarboxylic acid cycle to generate adenosine triphosphate
1 gram protein or carbohydrate = ____ kcal
1 gram fat = ___ kcal
During the first three days of fasting, which four processes maintain the blood glucose level?
Hepatic glycogenolysis, adipocyte free fatty acid release, muscle and liver free fatty acid use (instead of glucose), and hepatic gluconeogenesis
What molecules do skeletal muscles contribute for hepatic gluconeogenesis in order to maintain the blood glucose level?
Lactate and alanine
What are the only triacylglycerol molecules that can contribute to gluconeogenesis?
Glycerol, propionyl-CoA (from odd-chain free fatty acids)
Which compounds do adipose tissues contribute for hepatic gluconeogenesis in order to maintain the blood glucose level during the first three days of starvation?
Glycerol and propionyl-CoA (from free fatty acid metabolism)
What two metabolic processes does the liver undergo to maintain blood glucose level in the first three days of fasting/starvation?
Gluconeogenesis and glycogenolysis
Name the organ: After the third day of fasting, ketone bodies formed in the _____ supply the _____ and the ______ with energy.
Liver; brain; heart
What role does adipose tissue play in maintaining blood glucose levels in the first three days of fasting/starvation?
Release of free fatty acids that can be metabolized into contributions for hepatic gluconeogensis
Which tissues contribute the compounds required for hepatic gluconeogensis in order to maintain the blood glucose level during the first three days of fasting?
Peripheral tissue (lactate and alanine) and adipose tissue (free fatty acids)
True or False? More muscle protein is degraded during days 1-3 of starvation than after several weeks of starvation.
True; ketone bodies become the main source of energy for the brain after several weeks of starvation and so less muscle protein is degraded compared to the first three days
After several weeks of starvation, survival time is determined by the amount of _____ (muscle/fat) stores.
Once fat stores are depleted after several weeks of starvation, _____ (protein/glucose/free fatty acid) degradation accelerates, leading to organ failure and death.
What are the sources of adenosine triphosphate for muscles during brief exercise?
Stored adenosine triphosphate, creatine phosphate, and anaerobic glycolysis
In addition to the sources that can be used in seconds, from which sources do muscles derive adenosine triphosphate during exercise that lasts at least several minutes?
Stored adenosine triphosphate, creatine phosphate, anaerobic glycolysis, and oxidative phosphorylation
Which sources of adenosine triphosphate does the body use during exercise that lasts for hours?
Glycogen and free fatty acid oxidation
What are the purposes of the metabolic changes the body undergoes during starvation?
To supply glucose to the brain and preserve protein structures
What is the enzyme that esterifies plasma cholesterol?
What category of drugs inhibits HMG coenzyme A reductase?
What enzyme catalyzes the rate-limiting reaction in cholesterol synthesis?
What are the two essential fatty acids?
Linolenic acid and linoleic acid
What acid becomes essential in the absence of linoleic acid?
The formation of eicosanoids is dependent on the consumption of which fatty acids?
Essential fatty acids: linolenic and linoleic acid
Which enzyme is responsible for the degradation of dietary triglycerides?
Which enzyme is responsible for the degradation of triglycerides that are circulating as chylomicrons?
Which organs take up low-density lipoproteins from the circulation?
The liver and peripheral tissues with low-density lipoprotein receptors
Which enzyme is responsible for the degradation of triglycerides circulating as intermediate-density lipoproteins?
Hepatic triglyceride lipase
What is the enzyme responsible for converting nascent high-density lipoproteins into mature high-density lipoproteins?
What enzyme is responsible for the degradation of triglycerides that are stored within adipocytes?
What enzyme transfers cholesterol esters from high-density lipoproteins to other lipoproteins?
Cholesteryl ester transfer protein
What organ releases chylomicrons into the circulation?
The gastrointestinal tract
Name three lipoproteins that receive cholesterol esters from high-density lipoprotein via cholesteryl ester transfer protein.
Very-low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein
What enzyme converts chylomicrons into chylomicron remnants?
What organ takes up chylomicron remnants from the circulation?
What organ releases very-low-density lipoprotein into the circulation?
What enzymes convert intermediate-density lipoproteins into low-density lipoproteins?
Hepatic triglyceride lipase and lipoprotein lipase
What enzyme converts very-low-density lipoproteins into intermediate-density lipoproteins?
Which apolipoprotein activates lecithin-cholesterol acyltransferase?
Apolipoprotein A-I Activates LCAT
Which apolipoprotein binds to the low-density lipoprotein receptor on the liver?
Apolipoprotein B-100 Binds the LDL receptor
What apolipoprotein mediates very-low-density lipoprotein secretion?
Which apolipoprotein acts as a cofactor for lipoprotein lipase?
Apolipoprotein C-II is a Cofactor for LPL
Which apolipoprotein mediates remnant uptake?
Apolipoprotein E mediates Extra (remnant) uptake
What molecules do lipoproteins contain?
Cholesterol, triglycerides, and phospholipids
Which lipoprotein delivers dietary triglycerides to peripheral tissues?
Which lipoprotein is secreted only by intestinal epithelial cells?
Which apolipoprotein mediates the secretion of chylomicrons from the gastrointestinal tract?
Which lipoprotein delivers hepatic triglycerides to peripheral tissues?
Which organ secretes very-low-density lipoprotein into the bloodstream?
Name the two major lipoprotein carriers of cholesterol
Low-density lipoprotein and high-density lipoprotein
What lipoprotein carries cholesterol from the liver to the tissues?
Low-density lipoprotein (remember: LDL is Lousy)
What lipoprotein carries cholesterol from the tissues to the liver?
High-density lipoprotein (remember: HDL is Healthy)
Which apolipoprotein on low-density lipoprotein mediates uptake into the liver?
Which lipoprotein delivers dietary cholesterol to the liver?
Chylomicrons (as chylomicron remnants)
Which lipoprotein mediates the transport of cholesterol from the periphery to the liver (reverse transport)?
Name four apolipoproteins found on chylomicrons.
B-48, A-IV, C-II, and E
Which lipoprotein acts as a reservoir of apolipoprotein C and apolipoprotein E?
Which lipoprotein is formed by the degradation of very-low-density lipoprotein in the periphery by lipoprotein lipase (via IDL as an intermediate)?
What three apolipoproteins are found on very-low-density lipoprotein?
Apolipoprotein B-100, apolipoprotein C-II, and apolipoprotein-E
Which lipoprotein is formed by the degradation of very-low-density lipoprotein?
What lipoprotein is secreted by both intestinal epithelial cells and the liver?
Which lipoprotein delivers triglycerides and cholesterol to the liver for degradation into low-density lipoprotein?
What are the two apolipoproteins found on intermediate-density lipoprotein?
B-100 and E
What is another name for type I dyslipidemia?
An altered apolipoprotein C-II that does not function properly produces which type of familial dyslipidemia?
Type I (hyperchylomicronemia); C-II is a cofactor for lipoprotein lipase and if altered, the body is unable to metabolize chylomicrons