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PHAR 412

Metabolism of Carbohydrates, Lipids, Proteins, and Amino Acids

What is the function of LCAT (lecithin-cholesterol acyltransferase)? It converts free cholesterol to cholesterol esters.
What is the function of ABCA1A (ATP binding cassette protein A1)? Incorporates phospholipid and unesterified cholesterol into apoA-I.
What is the function of SR-BI (class B scavenger receptor BI)? Mediates cholesterol uptake in liver via apo A-I.
What is the function of PLTP (phospholipid transfer protein)? Transfers phospholipids from apoB-containing remnant particles to HDL. Removes excess phospholipid from shrinking apoB particles and replaces phospholipids on HDL that are consumed by LCAT.
What is the function of CETP (cholesterol ester transfer protein)? Transfers cholesterol esters from mature HDL to remnant apoB particles in exchange for triacylglycerol.
What are three bile acid sequestrants? Cholestyramine, Colestipol, Colesevelam
What do bile acid sequestrants do? Bind bile acids in intestine preventing reabsorption ---> increases bile acid production in liver (7a-hydroxylase activity) ---> decreases hepatic cholesterol ---> increases LDL receptors ---> decreases LDL
How does Tricor affect lipid levels? Fibrates activate PPARa (peroxisome proliferator-activated receptor), a nuclear receptor ---> increases LPL expression ---> decreases triglycerides and increases HDL
What is the mechanism of action for Niacin? Increases apoA-1 half-life ---> increases HDL
What is the threshold of glucose concentration that will stimulate insulin secretion? 80 mg/dL
How soon after a carbohydrate-rich meal do insulin levels reach their peak? ~1 hour
How long do insulin levels stay elevated? ~3 hours
How is insulin metabolized? The serum half-life of insulin is 5-7 minutes. It is broken down by degrading enzymes in the liver.
What are the target tissues of insulin? Muscle and adipose
What stimuli trigger glucagon secretion? Amino acids, epinephrine & norepinephrine, cortisol
True/False: Much less insulin is secreted in response to amino acids than is secreted in response to carbohydrates. True
What happens to glucagon levels after a carbohydrate-rich meal? Decreases
What happens to glucagon levels after a protein-rich meal? Increases
What are the target tissues of glucagon? Liver and adipose
How does the glucagon receptor work? Glucagon binds GPCR ---> activates PKA
What is the cause of adrenergic symptoms? Blood glucose lower than 60 mg/dL causes adrenergic hormone release (epinephrine & norepinephrine).
What is the cause of neuroglycopenic symptoms? Severe hypoglycemia lower than 60 mg/dL causing a lack of glucose to neurons.
What is postprandial/reactive hypoglycemia? Low blood sugar 2-4 hours after a meal due to prolonged/elevated insulin response.
What symptoms does postprandial/reactive hypoglycemia cause? Adrenergic symptoms
True/False: Fasting hypoglycemia may result in both adrenergic and neuroglycopenic symptoms. True
What are possible causes of fasting hypoglycemia? Disorders in glucose mobilization, hypersecretion of insulin, drug-induced hypoglycemia
What are disorders in glucose mobilization? Glycogen storage diseases, classical galactosemia, hereditary fructose intolerance, gluconeogenesis disorders, severe liver disease, glucagon or epinephrine deficiency.
What can cause hypersecretion of insulin? Tumor of the B-cells (insulinoma), neonatal hypoglycemia
What is neonatal hypoglycemia? Immature glycogen stores and deficiencies of gluconeogenesis enzymes. Occurs in infants of mothers with gestational diabetes (hyperinsulinemia).
What is drug-induced hypoglycemia? Exogenous insulin administration, alcohol-induced hypoglycemia
What are biochemical abnormalities that could lead to diabetes? Pancreatic disorders, endocrine disorders, drugs & toxins, autoimmune destruction of B-cell (Type I diabetes), insulin resistance followed by loss of B-cells (Type II diabetes).
What is cystic fibrosis? Fibrotic destruction of islets
Diabetes is diagnosed as a result of a fasting plasma glucose greater than or equal to: 126 mg/dL
What dosage of glucose is given to the patient during an OGTT? 75 g
"Impaired glucose tolerance" or "pre-diabetes" is diagnosed when a blood glucose sample is measured between what range? 140 to 200 mg/dL
What are common symptoms of diabetes? Polydipsia, polyuria, weight loss, hunger and blurred vision.
True/False: Glucose binds to the terminal amino groups of hemoglobin. True
What would glycogen storage diseases cause? Hypoglycemia
What would classical galactosemia cause? Hypoglycemia
What would hereditary fructose intolerance cause? Hypoglycemia
What would gluconeogenesis enzyme deficiency cause? Hypoglycemia
What would sever liver disease cause? Hypoglycemia
What would glucagon/epinephrine deficiency cause? Hypoglycemia
What would insulinoma cause? Hypoglycemia
What would immature glycogen stores cause? Hypoglycemia
What condition would infants of mothers with gestational diabetes have? Hypoglycemia
What would an insulin overdose cause? Hypoglycemia
What would alcoholism with poor food intake cause? Hypoglycemia
What would pancreatitis cause? Hyperglycemia
What would cystic fibrosis cause? Hyperglycemia
What would hemochromatosis cause? Hyperglycemia
What would an adrenal gland tumor cause? Hyperglycemia
What would Cushing's syndrome cause? Hyperglycemia
What would glucagonoma cause? Hyperglycemia
What would glucocorticoids cause? Hyperglycemia
What would loss-of-function of insulin receptor mutations cause? Hyperglycemia
What is the order of origin of blood glucose from phase I to phase V? (I) Exogenous, (II) glycogen, (III) gluconeogenesis, (IV) gluconeogenesis (from glucose & ketone bodies), (V) gluconeogenesis (from ketone bodies & glucose)
What tissues use glucose in what phases? (I) All, (II) all but liver, (III), all but liver, muscle, adipose, (IV) brain, RBCs, muscle, (V) brain (diminished), RBCs
What molecule does the liver use for ketogenesis? Acetyl-CoA
What tissue supplies acetyl-CoA for ketogenesis? Adipose
Which is more active in the fasting state: HSL or LPL? Why? HSL. HSL is activated by glucagon and stimulates fatty acid release. LPL breaks down dietary fat in chylomicrons to be taken up in adipose tissue.
What tissue provides ketone bodies to fuel muscle and brain in the fasting state? Liver
Does the muscle proteolysis rate tend to increase or decrease during the late fasting state? Decrease
Glargine (Lantus) Slow
Glulisine (Apidra) Rapid
What factors contribute to the slow action of insulin glargine (Lantus)? Mutation of 3 amino acids decreases absorption at neutral pH.
What modification accounts for the prolonged action of insulin detemir (Levemir)? Attachment of a fatty acid causes aggregation with themselves and albumin.
Glargine (Lantus) Slow
Glulisine (Apidra) Rapid
What factors contribute to the slow action of insulin glargine (Lantus)? Mutation of 3 amino acids decreases absorption at neutral pH.
What modification accounts for the prolonged action of insulin detemir (Levemir)? Attachment of a fatty acid causes aggregation with themselves and albumin.
What two insulin delivery devices are compact and discreet? Insuiln pens, pumps, and inhalation devices
What two insulin delivery devices are most expensive? Jet injectors and insulin pumps
Which insulin delivery device requires regular cleaning? Jet injectors
Which insulin delivery device can cause pain and bruising? Jet injectors
Which insulin delivery device can result in rapid loss of glycemic control of there is a malfunction? Insulin pump
Which insulin delivery device requires frequent monitoring of blood sugar? Insulin pump
What three insulin delivery devices have needles? Syringes, pens, and pumps
Why would insulin secretagogues be a poor treatment choice for type 1 diabetes? Type 1 diabetics have a deficiency of B-cells.
True/False: Insufficient insulin to induce the lipoprotein lipase of adipose cells contributes to increased blood triglyceride levels in untreated diabetics. True
True/False: Amino acids from muscles can be converted to glucose by gluconeogenesis in a patient with untreated type 2 diabetes? True
What is the function of incretins? Hormones that enhance glucose-stimulated insulin release, reduce glucagon, and slow gastric emptying.
What is an example of a thiazolidinedione? Pioglitazone (Actos)
What is an example of a meglitanide? Nateglinide (Starlix)
What is the mechanism of action for a-glucosidase inhibitors? Inhibition of carbohydrate digestion
What is the mechanism of action for DPP-IV inhibitors? Stimulation of glucose-dependent insulin secretion, reduction of glucagon, delay gastric emptying
What are two examples of a-glucosidase inhibitors? Acarbose (Precose), Miglitol (Glyset)
What are three examples of DPP-IV inhibitors? Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta)
What is the mechanism of action for biguanides? Inhibits gluconeogenesis
What is an example of a biguanide? Metformin (Glucophage)
What is the mechanism of action for sulfonylureas? Stimulates insulin secretion
What is an example of a sulfonylurea? Glimepiride (Amaryl)
What is the mechanism of action for hormone mimetics? Mimics a euglycemic hormone
What are three examples of hormone mimetics? Exentide (Byetta), Luraglutide (Victoza), Pramlintide (Symlin)
What is Canagliflozin (Invokana)? SGLT2 inhibitor
What diabetes treatments have the risk of hypoglycemia? Hormone mimetics, sulfonylureas, meglitanides
What diabetic treatment has an ADR of causing or worsening congestive heart failure? Thiazolidinediones
What diabetic treatment should not be used in patients with renal dysfunction? Biguanide and SGLT2 treatment
Which class of drug is associated with tachyphylaxis? Sulfonylureas
What does gastrin do? Stimulates release of HCl and pepsinogen.
What does secretin do? Stimulates HCO3 secretion from pancreas.
What does cholecystokinin do? Stimulates enzyme secretion and release of bile.
Where is trypsinogen synthesized? Small intestine
What activates trypsinogen to trypsin? Enterokinase/trypsin
Where is pepsinogen synthesized? Chief cells in stomach.
What activates pepsinogen to pepsin? Low pH
Where is chymotrypsinogen synthesized? Small intestine
What activates chymotrypsinogen to trypsinogen? Enterokinase/trypsin
Where is proelastase synthesized? Small intestine
What activates proelastase to elastase? Enterokinase/trypsin
What is the function of trypsin, pepsin, chymotrypsin, elastase, and enterokinase? Hydrolyze peptide bonds within chains (endopeptidases).
What is the function of carboxypeptidase A and B? Remove amino acids at C-terminus (exopeptidase).
What are the sources of protein in the intestine and their contribution? Food (50%), pancreatic secretions (25%), desquamated mucosal cells (25%).
What is the cofactor for transaminases? Amino group (NH4)
What cofactors are required for glutamate dehydrogenase? NAD+
What cofactors are formed from glutamate dehydrogenase? NADH, NH3
What direction is favored if GDP and ADP levels are high, glutamate or a-ketoglutarate? a-ketoglutarate
How can nitrogen in alanine provide free NH4? Alanine in muscle ---> blood ---> liver, then converted to pyruvate, giving NH3 to glutamate. Glutamate yields free NH4. NH4 is free before used as a cofactor the urea cycle.
What cofactors are required for glutamine synthesis from glutamate? NH4 and ATP
How does phenylbutyrate work to lower ammonia levels? Phenylbutyrate combines with glutamine and is excreted.
True/False: Glutamate dehydrogenase can incorporate and release free nitrogen. True
True/False: Hyperammonemia is likely due to an imbalance in the equilibrium of the reaction catalyzed by glutamate dehydrogenase. True
Where is orotate derived from? Carbamoyl phosphate
True/False: The liver produces significant quantities of heme for cytochrome P450s. True
True/False: Creatinine is used as a measure of kidney function because it is produced at a regular rate and is constantly being excreted by the kidney. True
True/False: Ferrous iron is reduced and inserted into protoporphyrin IX to form heme. True
What two molecules come together for form heme? Glycine and succinyl-CoA
How many molecules of an amino acid are required to form one molecule of heme? 8
True/False: An increase in unconjugated bilirubin could result from increased hemolysis. True
What bilirubin derivatives are found in urine and feces? Urobilinogen, urobilin, stercobilin
What is the ligand for adrenergic receptors? Epinephrine or norepinephrine
Why does histamine cause vasodilation via H1 coupled to Gq when Gq normally causes vasoconstriction? Gq activates PLC, which increases IP3, increasing calcium, activating eNOS, which increases nitric oxide. Nitric oxide causes relaxation of smooth muscle (vasodilation).
What do adrenergic a receptors cause? Vasoconstriction
What do adrenergic B receptors cause? Bronchodilation
What are the receptor types for adrenergic receptors? Gq (a1), Gi (a2), Gs (B)
What is the ligand for nicotinic receptors? Acetylcholine
What do nicotinic receptors cause? Depolarization/excitation in PNS & CNS.
What is the receptor type for nicotinic receptors? Ion channel (Ca2+, Na+, K+)
What does muscarinic M3 cause? Vasoconstriction, saliva stimulation
What are the serotonin receptor types and what do they cause? 5HT1 (Gi) ---> vasoconstriction, 5HT2 (Gq) ---> hallucinations, 5HT3 (ion channel) ---> depolarization/excitation, 5HT4 (Gs), 5HT5 (Gs), 5HT6 (Gs), 5HT7 (Gs)
What is the effect of D1 receptors? Vasodilation
What is the effect of D2 receptors? CNS - motor function, emotion reward, impulse
What is the effect of H2 receptors? Increase gastric acid secretion
True/False: An antagonist of D2 receptors is more likely to be associated with extrapyrmamidal symptoms. True
By what mechanism does GABAb hyperpolarize? Decreases intracellular K+
What does an agonist of 5HT3 cause? Nausea and vomiting
eNOS is activated by: Calcium
What is required to maintain benzodiazepine binding at GABAa? y2
Created by: sdeck86



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