Chapters 26 - 30

ceramide

(serine + palmitate) + fatty acid sphingosine + fatty acid

Cotransport

2 substrates cross membrane while bound to a carrier protein

*The answer is D.* Once insulin is injected, glucose transport into the peripheral tissues will be enhanced. If the patient does not eat, the normal fasting level of glucose will drop even further because of the injection of insulin, which increases the movement of glucose into muscle and fat cells. The patient becomes hypoglycemic, as a result of which epinephrine is released from the adrenal medulla. This, in turn, leads to the signs and symptoms associated with high levels of epinephrine in the blood. Answers A and B are incorrect because as glucose levels drop, glucagon will be released from the pancreas to raise blood glucose levels, which would alleviate the symptoms. Answer E is incorrect because ketone body production does not produce hypoglycemic symptoms, nor would they be significantly elevated only a few hours after the insulin shock the patient is experiencing.

26-1. A patient with type 1 diabetes mellitus takes an insulin injection before eating dinner but then gets distracted and does not eat. Approximately 3 hours later, the patient becomes shaky, sweaty, and confused. These symptoms have occurred because of which of the following? A. Increased glucagon release from the pancreas B. Decreased glucagon release from the pancreas C. High blood glucose levels D. Low blood glucose levels E. Elevated ketone body levels

*The answer is B.* When glucagon binds to its receptor, the enzyme adenylate cyclase is eventually activated (through the action of G proteins), which raises cAMP levels in the cell. The cAMP phosphodiesterase opposes this rise in cAMP, and hydrolyzes cAMP to 5'-AMP. If the phosphodiesterase is inhibited by caffeine, cAMP levels would stay elevated for an extended period, enhancing the glucagon response. The glucagon response in liver is to export glucose (thus, E is incorrect) and to inhibit glycolysis (thus, D is incorrect). cAMP activates protein kinase A, making answer C incorrect as well. The effect of insulin is to reduce cAMP levels (thus, A is incorrect).

26-2. Caffeine is a potent inhibitor of the enzyme cAMP phosphodiesterase. Which of the following consequences would you expect to occur in the liver after drinking two cups of strong espresso coffee? A. A prolonged response to insulin B. A prolonged response to glucagon C. An inhibition of protein kinase A D. An enhancement of glycolytic activity E. A reduced rate of glucose export to the circulation

*The answer is B.* Insulin release is dependent on an increase in the [ATP]/[ADP] ratio within the pancreatic β-cell. In MODY, the mutation in glucokinase results in a less active glucokinase at glucose concentrations that normally stimulate insulin release. Thus, higher concentrations of glucose are required to stimulate glycolysis and the tricarboxylic acid (TCA) cycle to effectively raise the ratio of ATP to ADP. Answer A is incorrect because cAMP levels are not related to the mechanism of insulin release. Answer C is incorrect because, initially, transcription is not involved, as insulin release is caused by exocytosis of preformed insulin in secretory vesicles. Answer D is incorrect because the pancreas will not degrade glycogen under conditions of high blood glucose, and answer E is incorrect because lactate does not play in role in stimulating insulin release.

26-3. Assume that an increase in blood glucose concentration from 5 to 10 mM would result in insulin release by the pancreas. A mutation in pancreatic glucokinase can lead to maturity-onset diabetes of the young (MODY) because of which of the following within the pancreatic β-cell? A. A reduced ability to raise cAMP levels B. A reduced ability to raise ATP levels C. A reduced ability to stimulate gene transcription D. A reduced ability to activate glycogen degradation E. A reduced ability to raise intracellular lactate levels

*The answer is A.* The brain requires glucose because fatty acids cannot readily cross the blood-brain barrier to enter neuronal cells. Thus, glucose production is maintained at an adequate level to allow the brain to continue to burn glucose for its energy needs. The other organs listed as possible answers can switch to the use of alternative fuel sources (lactate, fatty acids, amino acids) and are not as dependent on glucose for their energy requirements as is the brain.

26-4. Which one of the following organs has the highest demand for glucose as a fuel? A. Brain B. Muscle (skeletal) C. Heart D. Liver E. Pancreas

*The answer is E.* Muscle does not express glucagon receptors, so they are refractory to glucagons' actions. Muscle does, however, contain GTP (made via the TCA cycle), G proteins, protein kinase A, and adenylate cyclase (epinephrine stimulation of muscle cells raises cAMP levels and activates protein kinase A).

26-5. Glucagon release does not alter muscle metabolism because of which of the following? A. Muscle cells lack adenylate cyclase. B. Muscle cells lack protein kinase A. C. Muscle cells lack G-proteins. D. Muscle cells lack guanosine triphosphate (GTP). E. Muscle cells lack the glucagon receptor.

*The answer is E.* The GLUT 5 transporter has a much higher affinity for fructose than glucose and is the facilitator of choice for fructose uptake by cells. The other GLUT transporters do not transport fructose to any significant extent.

27-1. The facilitative transporter that is most responsible for transporting fructose from the blood into cells is which of the following? A. GLUT 1 B. GLUT 2 C. GLUT 3 D. GLUT 4 E. GLUT 5

*The answer is A.* The pancreas produces α-amylase, which digests starch in the intestinal lumen. If pancreatic α-amylase cannot enter the lumen because of pancreatitis, the starch will not be digested to a significant extent. (The salivary α-amylase begins the process, but only for the time during which the food is in the mouth, as the acidic conditions of the stomach destroy the salivary activity.) The discomfort arises from the bacteria in the intestine, digesting the starch and producing acids and gases. Lactose, sucrose, and maltose are all disaccharides that would be cleaved by the intestinal disaccharidases located on the brush border of the intestinal epithelial cells (thus, B, D, and E are incorrect). These activities might be slightly reduced, as the pancreas would also have difficulty excreting bicarbonate to the intestine, and the low pH of the stomach contents might reduce the activity of these enzymes. However, these enzymes are present in excess and will eventually digest the disaccharides. Fiber cannot be digested by human enzymes, so answer C is incorrect.

27-2. An alcoholic patient developed pancreatitis that affected his exocrine pancreatic function. He exhibited discomfort after eating a high-carbohydrate meal. The patient most likely had a reduced ability to digest which of the following? A. Starch B. Lactose C. Fiber D. Sucrose E. Maltose

*The answer is C.* Insulin is required to stimulate glucose transport into muscle and fat cells but not into brain, liver, pancreas, or red blood cells. Thus, muscle would be feeling the effects of glucose deprivation and would be unable to replenish its own glycogen supplies as a result of its inability to extract blood glucose, even though blood glucose levels would be high.

27-3. A type 1 diabetic neglects to take his insulin injections while on a weekend vacation. Cells of which tissue will be most greatly affected by this mistake? A. Brain B. Liver C. Muscle D. Red blood cells E. Pancreas

*The answer is E.* Flour contains starch, which will lead to glucose production in the intestine. Milk contains lactose, a disaccharide of glucose and galactose, which will be split by lactase in the small intestine. Sucrose is a disaccharide of glucose and fructose, which is split by sucrase in the small intestine. Thus, glucose, galactose, and fructose will all be available in the lumen of the small intestine for transport through the intestinal epithelial cells and into the circulation.

27-4. After digestion of a piece of cake that contains flour, milk, and sucrose as its primary ingredients, the major carbohydrate products that enter the blood are which of the following? A. Glucose B. Fructose and galactose C. Galactose and glucose D. Fructose and glucose E. Glucose, galactose, and fructose

*The answer is A.* Salivary and pancreatic α-amylase will partially digest starch to glucose, but maltose and disaccharides will pass through the intestine and exit with the stool, as a result of the limited activity of the brush border enzymes. Because the amylase enzymes are working, there will only be normal levels of starch in the stool (thus, B is incorrect). Not all available glucose is entering the blood, so less insulin will be released by the pancreas (thus, E is incorrect), which will lead to less glucose uptake by the muscles and less glycogen production (thus, D is incorrect). Because neither lactose nor sucrose can be digested to a large extent in the intestinal lumen under these conditions, it would be difficult to have elevated levels of galactose or fructose in the blood (thus, C is incorrect).

27-5. A patient has a genetic defect that causes intestinal epithelial cells to produce disaccharidases of much lower activity than normal. Compared with a normal person, after eating a bowl of milk and oatmeal sweetened with table sugar, this patient will exhibit higher levels of which of the following? A. Maltose, sucrose, and lactose in the stool B. Starch in the stool C. Galactose and fructose in the blood D. Glycogen in the muscles E. Insulin in the blood

*The answer is B.* Glycogen phosphorylase produces glucose 1-phosphate; the debranching enzyme hydrolyzes branch points and thus releases free glucose. Ninety percent of the glycogen contains α-1,4-bonds and only 10% are α-1,6-bonds, so more glucose 1-phosphate will be produced than glucose.

28-1. The degradation of glycogen normally produces which of the following? A. More glucose than glucose 1-phosphate B. More glucose 1-phosphate than glucose C. Equal amounts of glucose and glucose 1-phosphate D. Neither glucose or glucose 1-phosphate E. Only glucose 1-phosphate

*The answer is D.* If, after fasting, the branches were shorter than normal, glycogen phosphorylase must be functional and capable of being activated by glucagon (thus, A and B are incorrect). The branching enzyme (amylo-4,6-transferase) is also normal because branch points are present within the glycogen (thus, E is incorrect). Because glycogen is also present, glycogenin is present in order to build the carbohydrate chains, indicating that C is incorrect. If the debranching activity is abnormal (the amylo-1,6-glucosidase), glycogen phosphorylase would break the glycogen down up to four residues from branch points and would then stop. With no debranching activity, the resultant glycogen would contain the normal number of branches, but the branched chains would be shorter than normal.

28-2. A patient has large deposits of liver glycogen, which after an overnight fast, had shorter-than-normal branches. This abnormality could be caused by a defective form of which one of the following proteins or activities? A. Glycogen phosphorylase B. Glucagon receptor C. Glycogenin D. Amylo-1,6-glucosidase E. Amylo-4,6-transferase

*The answer is C.* The patient has McArdle disease, a glycogen storage disease caused by a deficiency of muscle glycogen phosphorylase. Because he or she cannot degrade glycogen to produce energy for muscle contraction, he or she becomes fatigued more readily than a normal person (thus, A is incorrect), the glycogen levels in her muscle will be higher than normal as a result of the inability to degrade them (thus, D is incorrect), and his or her blood lactate levels will be lower because of the lack of glucose for entry into glycolysis. He or she will, however, draw on the glucose in his or her circulation for energy, so his or her forearm blood glucose levels will be decreased (thus, B is incorrect), and because the liver is not affected, blood glucose levels can be maintained by liver glycogenolysis (thus, E is incorrect).

28-3. An adolescent patient with a deficiency of muscle phosphorylase was examined while exercising his or her forearm by squeezing a rubber ball. Compared with a normal person performing the same exercise, this patient would exhibit which of the following? A. Exercise for a longer time without fatigue. B. Have increased glucose levels in blood drawn from his or her forearm. C. Have decreased lactate levels in blood drawn from his or her forearm. D. Have lower levels of glycogen in biopsy specimens from his or her forearm muscle. E. Hyperglycemia

*The answer is A.* After ingestion of glucose, insulin levels rise, cAMP levels within the cell drop (thus, E is incorrect), and protein-phosphatase-I is activated (thus, D is incorrect). Glycogen phosphorylase a is converted to glycogen phosphorylase b by the phosphatase (thus, B is incorrect), and glycogen synthase is activated by the phosphatase. Red blood cells continue to use glucose at their normal rate, thus lactate formation will remain the same (thus, C is incorrect).

28-4. In a glucose tolerance test, an individual in the basal metabolic state ingests a large amount of glucose. If the individual is normal, this ingestion should result in which of the following? A. An enhanced glycogen synthase activity in the liver B. An increased ratio of glycogen phosphorylase a to glycogen phosphorylase b in the liver C. An increased rate of lactate formation by red blood cells D. An inhibition of PP-1 activity in the liver E. An increase of cAMP levels in the liver

*The answer is F.* In the absence of insulin, glucagonstimulated activities predominate. This leads to the activation of protein kinase A, the phosphorylation and inactivation of glycogen synthase, the phosphorylation and activation of phosphorylase kinase, and the phosphorylation and activation of glycogen phosphorylase.

28-5. Consider a person with type 1 diabetes who has neglected to take insulin for the past 72 hours and has not eaten much as well. Which of the following best describes the activity level of hepatic enzymes involved in glycogen metabolism under these conditions? Glycogen synthase; phosphorylase kinase; glycogen phosphorylase A. active; active; active B. active; active; inactive C. active; inactive; inactive D. inactive; inactive; inactive E. inactive; active; inactive F. inactive; active; active

*The answer is D.* The aldolase B gene has two alleles. One or both may have mutations. Because HFI is recessive, both alleles must be mutated for the disease to be expressed. Examination of the gel shows that the normal gene is cleaved by ahaII to produce a 306-bp (base pair) restriction fragment. When a mutation creates a new ahaII site within the gene, this 306-bp fragment is cleaved into two fragments of 183 and 123 bp (which together contain 306 bp). The husband and Jill, thus, are carriers. They have one normal allele that produces the 306-bp fragment and one that has an additional ahaII site, which is cleaved to yield the two fragments of 183 and 123 bp. The wife and Jack have the disease. Both of their alleles have the additional ahaII site and produce only 183- and 123-bp fragments.

29-1. Hereditary fructose intolerance (HFI) is a rare recessive genetic disease that is most commonly caused by a mutation in exon 5 of the aldolase B gene. The mutation fortuitously creates a new ahaII recognition sequence. To test for the mutation, DNA was extracted from a wife, husband, and their two children, Jack and Jill. The DNA for exon 5 of the aldolase B gene was amplified by polymerase chain reaction (PCR), cleaved with ahaII, treated with alkali, subjected to electrophoresis on an agarose gel, and stained with a dye that binds to DNA. Which of the following conclusions can be made from the data presented? A. Both of the children have the disease. B. Neither of the children has the disease. C. Jill has the disease, Jack does not. D. Jack has the disease, Jill does not. E. There is not enough information to make a determination.

*The answer is C.* This man could be the father of both children. He could provide either a normal gene (which produces a 306-bp ahaII fragment) or a mutant gene (which produces 183- and 123-bp ahaII fragments) to his offspring. This mother could provide only the mutant gene (of which she has two copies). Jill is a carrier. She received the mutant gene from her mother and could have received the normal gene from this man. Jack has the disease. He received one mutant gene from his mother and another from his father.

29-2. On examining the gel himself, the husband became concerned that he might not be the biologic father of one or both of the children. From the pattern on the gel, you can reasonably conclude which of the following? A. He is probably not Jill's father. B. He is probably not Jack's father. C. He could be the father of both children. D. He is probably not the father of either child. E. There is not enough information to make a determination.

*The answer is C.* Transketolase requires thiamine pyrophosphate as a cofactor, whereas none of the other enzymes listed does. Thus, if an individual has a thiamine deficiency, transketolase activity as isolated from a patient's blood cells will be enhanced by the addition of thiamine; in well-nourished individuals, the addition of thiamine will not enhance transketolase activity.

29-3. An alcoholic is brought to the emergency room in a hypoglycemic coma. Because alcoholics are frequently malnourished, which of the following enzymes can be used to test for a thiamine deficiency? A. Aldolase B. Transaldolase C. Transketolase D. Glucose-6-phosphate dehydrogenase E. UDP-galactose epimerase

*The answer is B.* Fructose is converted to fructose 1-phosphate by fructokinase, and aldolase B in the liver splits the fructose 1-P into glyceraldehyde and dihydroxyacetone phosphate. Thus, the major regulated step of glycolysis, PFK-1, is bypassed and PEP is rapidly produced. As the [PEP] increases, pyruvate kinase produces pyruvate. As the glyceraldehyde-3-phosphate dehydrogenase reaction is proceeding rapidly (remember that fructokinase is a high Vmax enzyme, so there is a lot of substrate proceeding through the glycolytic pathway), the intracellular [NADH]/[NAD_] ratio is high, and the pyruvate produced is converted to lactate in order to regenerate NAD_. Thus, the pyruvate kinase step is not bypassed (thus, A is incorrect). Neither aldolase B nor lactate dehydrogenase is allosterically regulated (thus, C and D are incorrect), and even though the [ATP]:[ADP] ratio is high in the liver under these conditions, the ratio does not affect lactate formation (thus, E is incorrect).

29-4. Intravenous fructose feeding can lead to lactic acidosis caused by which of the following? A. Bypassing the regulated pyruvate kinase step B. Bypassing the regulated phosphofructokinase-1 (PFK-1) step C. Allosterically activating aldolase B D. Allosterically activating lactate dehydrogenase E. Increasing the [ATP]:[ADP] ratio in liver

*The answer is B.* Reduction of sugar aldehydes to alcohols requires NADPH, which is generated primarily by the pentose phosphate pathway. 6-Phosphogluconate is not a polyol (thus, A is incorrect; 6-phosphogluconate is glucose oxidized at position 1 to form a carboxylic acid); ribitol is not a product of the pentose phosphate pathway (thus, B is incorrect; ribulose 5-phosphate is a product of the pentose phosphate pathway); the HMP shunt uses glucose 6-phosphate as the starting material, not free glucose as in the sorbitol pathway (thus, D and E are incorrect).

29-5. The polyol pathway of sorbitol production and the hexose monophosphate (HMP) shunt pathway are linked by which of the following? A. The HMP shunt produces 6-phosphogluconate, an intermediate in the polyol pathway. B. The HMP shunt produces NADPH, which is required for the polyol pathway. C. The HMP shunt produces ribitol, an intermediate of the polyol pathway. D. Both pathways use glucose as the starting material. E. Both pathways use fructose as the starting material.

*The answer is B.* Galactose metabolism requires the phosphorylation of galactose to galactose 1-phosphate, which is then converted to UDP-galactose (which is the step that is defective in the patient), and then epimerized to UDP-glucose. Although the mother cannot convert galactose to lactose because of the enzyme deficiency, she can make UDP-glucose from glucose 6-phosphate, and once she has made UDP-glucose, she can epimerize it to form UDP-galactose and can synthesize lactose (thus, A is incorrect). However, because of her enzyme deficiency, the mother cannot convert galactose 1-phosphate to UDPgalactose or UDP-glucose, so the dietary galactose cannot be used for glycogen synthesis or glucose production (thus, C and D are incorrect). After ingesting milk, the galactose levels will be elevated in the serum because of the metabolic block in the cells (thus, E is incorrect).

30-1. Which of the following best describes a mother with galactosemia caused by a deficiency of galactose-1-phosphate uridylyltransferase? A. She can convert galactose to UDP-galactose for lactose synthesis during lactation. B. She can form galactose 1-phosphate from galactose. C. She can use galactose as a precursor to glucose production. D. She can use galactose to produce glycogen. E. She will have lower than normal levels of serum galactose after drinking milk.

*The answer is D.* Nucleotide sugars, such as UDPglucose, UDP-galactose, and CMP-sialic acid, donate sugars to the growing carbohydrate chain. The other activated sugars listed do not contribute to this synthesis.

30-2. The immediate carbohydrate precursors for glycolipid and glycoprotein synthesis are which of the following? A. Sugar phosphates B. Sugar acids C. Sugar alcohols D. Nucleotide sugars E. Acylsugars

*The answer is C.* Bilirubin is conjugated with glucuronic acid residues to enhance its solubility. Glucuronic acid is glucose oxidized at position 6; gluconic acid is glucose oxidized at position 1 and is generated by the HMP shunt pathway.

30-3. A newborn is diagnosed with neonatal jaundice. In this patient, the bilirubin produced lacks which of the following carbohydrates? A. Glucose B. Gluconate C. Glucuronate D. Galactose E. Galactitol

*The answer is C.* Glutamine donates the amide nitrogen to fructose 6-phosphate to form glucosamine 6-phosphate. None of the other nitrogen-containing compounds (A, B, and D) donate their nitrogen to carbohydrates. Dolichol contains no nitrogens and is the carrier for carbohydrate chain synthesis of N-linked glycoproteins.

30-4. The nitrogen donor for the formation of amino sugars is which of the following? A. Ammonia B. Asparagine C. Glutamine D. Adenine E. Dolichol

*The answer is C.* Sandhoff disease is a deficiency of both hexosaminidase A and B activity, resulting from loss of the β-subunit activity of these enzymes. The degradative step at which amino sugars need to be removed from the glycolipids would be defective, such that globoside and GM2 accumulate in this disease. The other answers are incorrect; GM1 does contain an amino sugar, but it is converted to GM2 before the block is apparent.

30-5. Which of the following glycolipids would accumulate in a patient with Sandhoff disease? A. GM1 B. Lactosylceramide C. Globoside D. Glucocerebroside E. GM3

Calmodulin

A calcium-binding multifunctional intermediate messenger protein expressed in all eukaryotic cells and mediates many crucial processes

Cyclic AMP

A second messenger derived from ATP and triggers specific cellular changes in metabolic regulation

Pinocytosis

A type of endocytosis in which the cell ingests extracellular fluid and its dissolved solutes.

Protein phosphatase

An enzyme that removes phosphate groups from (dephosphorylates) proteins, often functioning to reverse the effect of a protein kinase.

Protein kinase

An enzyme that transfers phosphate groups from ATP to a protein, thus phosphorylating the protein.

fetal tissue, brain, RBC, most cells; responsible for uptake required to sustain respiration in all cells

GLUT 1

liver, beta-cells; bidirectional transport; all 3 monosaccharides are transported from the intestinal mucosal cell into the portal circulation by GLUT2

GLUT 2

neurons, placenta; high-affinity allowing it to transport even in times of low concentration

GLUT 3

skeletal & cardiac muscle, fat; insulin-regulated

GLUT 4

hyaluronic acid, chrondroitins glycoproteins, mucins glycosaminoglycans, heparin glycolipids, gangliosides

Glucose is a precursor for many different molecules. Give examples

secretory vesicle w/membrane proteins secretory vesicle w/secreted protein lysosomal enzyme

Golgi apparatus is important in glycosylation of membranes. Identify three types of vesicles that budd off the golgi and their respective destinations

--MUSCLE CONTRACTION: AMP (+) glycogen phosphorylase --NERVE IMPULSES: neural impulses release Ca2+ from the sarcoplasmic reticulum which binds to calmodulin --EPINEPHRINE: cAMP, (+) PKA, (+) phosphorylase kinase, (+) glycogen phosphorylase

How do the activities of the exercising muscle activate glycogen phosphorylase

--a ligand (epinephrine) attaches to g-protein --the g-protein stimulates inositol triphosphate (IP3) --IP3 stimulates the ER to release calcium --Calcium binds to the calmodulin protein --Ca-calmodulin activates (+) calmodulin dependent protein kinase and (+) phosphorylase kinase --they both phosphorylase both (-) glycogen synthase and (+) glycogen phosphorylase

How does epinephrine mediate its effects on glycogen metabolism via calcium-calmodulin

Fructose metabolism occurs primarily in liver fructose (fructokinase)^ → fructose 1P F1P splits into DHAP & glyceraldehyde glyceraldehyde (triose kinase)^ → glyceraldehyde 3P (^uses 2 ATP & enters at same place where glucose has used 2 ATP)

How does fructose enter the glycolytic scheme

galactose →^ galactose 1P → ^^glucose 1P → glucose 6P ^uses 1 ATP & enters at same place where glucose has used 1 ATP ^^UDP-glucose → UDP-galactose

How does galactose enter the glycolytic scheme

--a ligand (glucagon or epinephrine) attaches to g-protein --the g-protein stimulates adenylate cyclase to turn ATP into cAMP --cAMP acts on protein kinase, activating it --protein kinase phosphorylases both (-) glycogen synthase and (+) glycogen phosphorylase

How does glucagon/epinephrine mediate its effects on glycogen metabolism via cAMP

Both glucose and fructose are transported by the facilitated glucose transporters on the luminal and serosal sides of the absorptive cells. Glucose and galactose are transported by the Na+-glucose cotransporters on the luminal (mucosal) side of the absorptive cells.

How does the gut transport of glucose and galactose differ from fructose transport

--Glucose enters beta cell and is metabolized to ATP --ATP inhibits K+ gated channel, and opens Ca+ gated channel --Calcium enters which stimulates fusion of insulin vesicle with cell membrane and exocytosis

How is insulin release mediated in the beta cell

glucose → sorbitol → fructose

How is sorbitol connected to glucose and fructose metabolism?

Isomaltase is an enzyme that breaks the bonds linking saccharides, which cannot be broken by amylase or maltase

How would you characterize the sucrose isomaltase enzyme

proteoglycans, glycoproteins, GAGs, glucuronides, bilirubin diglucuronide

Identify anabolic and degradative products of UDP-glucuronate

UDP-glucose UDP-galactose UDP-glucuronic acid UDP-xylose UDP-N acetylglucosamine UDP-N acetylgalactosamine CMP-N acetylneuraminic acid GDP-fucose GDP-mannose

Identify sugar nucleotide precursors for transferase enzymes

water soluble fibers form gels. examples include pectin, agar, carrageen Insoluble fiber does not absorb or dissolve in water. examples include cellulose, hemicellulose, lignin, xanthan

Identify the constituents of indigestible dietary fibers

activate glycogen phosphorylase and inactivate glycogen synthase by phosphorylation.

In fight/flight or low blood sugar, glucagon and epinephrine activate *protein kinase* which, in turn....

inactivate glycogen phosphorylase and activate glycogen synthase by dephosphorylation.

In the fed state, insulin response leads to activation of *phosphatase enzymes* which, in turn.....

glucuronides

Many xenobiotics, drugs, steroids and other compounds with hydroxyl groups and low solubility are converted to _____ so they are more water soluble and can be excreted

The action of the ROS on the cell membrane as well as mechanical stress from the lack of deformability (due to Heinz bodies, aggregates of cross-linked hemoglobin) result in hemolysis.

Outline the RBCs normal mechanism for neutralizing oxidant molecules. How might rise in oxidant stress from ROS lead to RBC hemolysis

1--enzyme *glycogen phosphorylase* cleaves glucosyl residues 1 by 1, adding phosphate. Pi → glucose 1P. This is halted 4 residues from a branch point 2--*debrancher enzyme* removes 3 residues and adds them to the end of a chain by a 1,4-link and also removes the remaining residue attached by a 1,6-link producing a free glucose

Outline the steps in glycogen degradation include the 2 crucial enzymes

1--*glycogen synthase*, the regulating enzyme, transfers a glucose to an existing branch by a 1,4-bond. UDP-glucose → UDP. 2--Repeat until the chain is about 11 residues in length. 3--Cleave a 6- to 8-residue piece using a *branching enzyme* 4--reattach this piece by a 1,6-bond 5--repeat as needed

Outline the steps in glycogen synthesis include the 2 crucial enzymes

Nucleotide diphosphate sugars are use in synthesis of glycogen, and in glycosyl transfer for synthesis of glycolipids, glycoproteins, proteoglycans and glucuronides

Outline the ways nucleotide diphosphate sugars are employed in metabolism

oxidative: 2 NADPH non-oxidative: ribose 5P, nucleotide biosynthesis glucose → glucose 6P → PPP → fructose 6P

Pentose phosphate pathway has an oxidative and non oxidative portion. What are the products of each portion of the pathway? Where is it?

insulin is released from the pancreas when blood sugar is high. --liver makes glycogen, protein and fatty acids; --fat cells make triaclyglycerols; --muscle cells make protein and glycogen. glucagon is released from the pancreas when blood sugar is low. --liver does gluconeogenesis, breaks down glycogen and releases glucose --fat cells break down triaclyglycerols and release fatty acids --Muscle cells are not affected by glucagon.

The body seeks to balance fuel availability with tissue need. In that regard how do the counterregulatory hormones, Insulin and glucagon mediate this fuel availability in liver, muscle and adipose tissues.

Glycans serve a variety of structural and functional roles in membrane and secreted proteins

What are functions of glycan

glycogen, UDP-galactose (+ glucose → lactose), proteoglycans, glycoproteins, glycolipids, UDP-glucuronate

What are the anabolic products of UDP glucose

--PPP is the major source of NADPH in cells --Provides reducing equivalents for fatty acid synthesis, cholesterol synthesis and fatty acid chain elongation. It is used to produce for superoxide (O2-) which kills microorganisms --Required for glutathione mediated defense against oxidative stress --Entry of glucose 6P into PPP is determined by NADPH concentrations

What are the metabolic uses of NADPH

salivary amylase breaks down starches to dextrins. pancreatic amylases break them down further to 4--9 gylucosyl units

What are the products of salivary and pancreatic amylases

the dietary disaccharides lactose and sucrose, as well as the products of starch digestion, are converted to monosaccharides by glycosidases. sucrose is cleaved via sucrase lactose is cleaved via lactase maltose is cleaved via maltase

What enzymes are responsible for disaccharide hydrolysis

ceramide

What is the precursor of all sphingolipids?

Tight junction

What part of the cell prevents leakage of material though the space between cells?

In brain, glucose transport (Glut 1&3) across blood brain barrier and into neural tissue is slow due to tight junctions, narrow intercellular spaces and continuous basement membrane so a drop in blood sugar below fasting can significantly affect glucose metabolism in brain

Why is glucose transport into neural tissue different from non neural tissue.

Glycoprotein

a compound containing carbohydrate (or glycan) covalently linked to protein

mucins

a family of high molecular weight, heavily glycosylated proteins

Proteoglycan

a subclass of glycoproteins in which the carbohydrate units are polysaccharides that contain amino sugars; composed of a protein core with one or more covalently attached glycosaminoglycan (GAG) chains

glycosyltransferase

catalyzes the formation of glycosidic bonds

GAG (Glycosaminoglycans )

composed of sugar acids and sugar amides; repeating units of substituted sugars that aggregate; Pathways for interconversion of sugars includes sugar acids and sugar amides found in _____

gangliosides

contain an oligosaccharide chain produced from UDP sugars and are produced in the Golgi

UDP Glucose

glucose 1P + UTP → PPi + _____ important intermediate in glycogen synthesis

UDP-glucose UDP-glucuronate

glucose is activated by a nucleotide attachment and called ____ which is then converted to this key intermediary in metabolism: ______

more active phosphaTase Takes away phosphate kinase gives it phosphate

glycogen phosphorylase is [more/less] active w/phosphate? phosphatase does what? kinase does what?

less active phosphaTase Takes away phosphate kinase gives it a phosphate

glycogen synthase is [more/less] active with phosphate? a phosphatase does what? kinase does what?

Xenobiotic

large hydrophobic molecules resembling fatty acids; Foreign substances that are not naturally found in the body

glycolipids

lipid with a carbohydrate covalently attached; involved in intercellular communication

Sugar acids

monosaccharides with a carboxyl group (-COOH)

Bilirubin

orange-yellow pigment in bile; formed by the breakdown of hemoglobin when red blood cells are destroyed

sphingosine

serine + palmitate

Glycogenin (primer)

small chain of glycogen needed to add glucose one by one

cerebrosides

synthesized from UDP Glucose or UDP Galactose and contain a single monosaccharide sugar

G Protein

the bridge between the hormone and the 2nd messenger; A GTP-binding protein that relays signals from a plasma membrane signal receptor, to other signal transduction proteins inside the cell.

glucose → glucose 6P^ → glucose 1P → UDP-glucose → glycogen ^has choices: glycolysis, PPP, glycogen, others

what are the intermediates from glucose to glycogen

glycogen^ → glucose 1P → glucose 6P^^ → glucose ^also releases a small amount of glucose ^^this last step happens only in liver, via glucose 6 phosphatase. otherwise, glucose 6P goes to PPP, glycolysis, or other pathways

what are the intermediates from glycogen to glucose

Glycogen synthase

what enzyme attaches UDP-glucose to existing glycogen chain

Debranching enzyme

what enzyme cleaves a 6- to 8-residue and reattaches it to another spot by a 1,6-link

Glycogen phosphorylase

what enzyme cleaves glucosyl residues 1 by 1 using phosphate from glycogen

Branching enzyme

what enzyme removes 2 residues and adds them to the end of a chain by a 1,4-link & then removes the single glucose attached by a 1,6-link

glycans

what is another name for polysaccharides?

no effect; they have no glucagon receptors

what is the effect of glucagon on skeletal muscle?

insulin -- beta cells gluc*a*gon -- *a*lpha cells

what liver cells make insulin? what liver cells make glucagon?