Module 10 Part 1 Flashcards

Question

25. In the active skeletal muscle, alanine is a breakdown product and is brought to the liver to become glucose. Glucose is then shipped back to the muscle. While alanine is being re-synthesized in the muscle, what else happens? a. Glutamate is formed and is used as an amino group carrier. b. 2-Oxoglutarate enters the Krebs cycle to produce more ATP. c. Glucose is stored as glycogen. d. Glutamine is formed from glutamate to release ammonia.

Answer 1

b. 2-Oxoglutarate enters the Krebs cycle to produce more ATP. d. Glutamine is formed from glutamate to release ammonia. Reference: https://www.researchgate.net/profile/Rob-Cairns/publication/311882673/figure/fig2/AS:646460806819840@1531139675033/The-potential-roles-of-IDH1-in-liver-During-prolonged-fasting-the-breakdown-of-skeletal.png

Answer 2

a. Systemic impairment of protein function Ketone bodies are a normal way to get energy from lipids (not water-soluble) through your blood. Ketone bodies are soluble so they can travel from the liver where they’re made throughout your body. The problem is just when you can’t keep up. During times of starvation or heavy prolonged exercise, the liver starts running out of OAA because you’re not feeding the pathway from sugar. And without OAA you can’t get acetyl-CoA into the pathway, so it instead takes the alternate ketone route. The ketones released can be taken in by cells throughout your body (even in your brain) and there’s enough OAA there (at least initially) to use it. References: Bibel, B. (2020, December 13). Leucine, ketogenic amino acids. Retrieved February 12, 2021, from https://thebumblingbiochemist.com/365-days-of-science/leucine-ketogenic-amino-acids/

Answer 3

``` c. Methionine Anemia is consistent with the patient's shortness of breath and fatigue, and certain types of anemia can be associated with paresthesia. Therefore, anemia is the most likely diagnosis of the given differential diagnosis. Anemias due to vitamin B12 or folate deficiency, chemotherapeutic agents, or myelodysplasia are commonly the result of impaired DNA synthesis and are typically characterized by large immature red blood cells and hyper segmented neutrophils. The MMA (Methylmalonic Acid)and homocysteine levels are used to confirm the diagnosis of vitamin B12 deficiency, especially in the setting of concurrent folate deficiency. In vitamin B12 deficiency, the MMA and homocysteine levels are both elevated. Only the homocysteine level is elevated in folate deficiency. Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Folate and B12 deficiencies result in low methionine and SAM and in high homocysteine, because they inhibit the regeneration of methionine from homocysteine References: Tweet, M. S., & Polga, K. M. (2010). 44-year-old man with shortness of breath, fatigue, and paresthesia. Mayo Clinic Proceedings. Mayo Clinic, 85(12), 1148–1151. ```

Answer 4

b. Pantothenic acid Pantothenic acid (B5) is required for coenzyme A formation which is a cofactor of pyruvate dehydrogenase. Reference: Doc VH’s lecture

Answer 5

b. More glucose-1-phosphate than glucose Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen. In glycogenolysis, the phosphorolytic cleavage of the 1 → 4 linkages of glycogen yields glucose-1-phosphate. Glucose-6-phosphate can be formed from glucose-1-phosphate via the enzyme phosphoglucomutase. In the liver, but not muscle, glucose-6-phosphatase hydrolyzes glucose-6-phosphate to glucose and is exported into the blood leading to an increase in the blood glucose concentration. Reference: Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2018). Harper's illustrated biochemistry (31st edition.). New York: Mcgraw-Hill Education.

Answer 6

a. PI3K-Akt pathway The PI3K-Akt pathway is principally involved in the internalization of glucose from the blood by the skeletal muscle which is mediated by insulin via a tyrosine kinase receptor. This is done by increasing the expression of glucose transporters (GLUTs) on the cell surface. Reference: Dr. Michael Nicolaus Q. Van Haute’s video lecture

Answer 7

a. Glycogenolysis and glycolysis Glycolysis is the main pathway of glucose metabolism. It can occur either aerobically or anaerobically Glycogenolysis is the process of breaking down glycogen. Muscle glycogen provides a source of glucose-6-phosphate for glycolysis in response to the need of ATP in muscle contraction. Reference: Chapter 17 & 18, Harper’s 13th Ed.

Answer 8

c. It converts fructose-1-phosphate to dihydroxyacetone phosphate and glyceraldehyde Aldolase B catalyzes the cleavage of Fructose-1-Phosphate to D-glyceraldehyde and Dihydroxyacetone phosphate. Aldolase B is the rate limiting enzyme of fructose metabolism because it has low affinity for Fructose-1-Phosphate. High levels must be accumulated for this reaction to move forward. Reference: Doc Micheal Van Haute’s Lecture on Pentose Phosphate Pathway and Alternative Carbohydrate Metabolism Pathway.

Answer 9

b. This requires an infinite supply of glycogen . Rate of ATP production from glycolysis is 100x faster than from oxidative phosphorylation. This particularly true with skeletal muscle which has its own glycogen stores. However, glycogen stores are rapidly depleted. Reference: Dr. Van Haute’s Lecture on Carbohydrate Metabolism: Glycolysis

Answer 10

a. untreated hemolytic anemia Indirect bilirubin (unconjugated) is the difference between total bilirubin and direct bilirubin. Common causes of higher indirect indirect bilirubin include: Hemolytic anemia Bleeding into the skin caused by injury Bleeding in the lung caused by a blood clot A gene problem that causes slightly higher indirect bilirubin levels without other signs or symptoms of disease Reference: University of Rochester Medical Center - Health Encyclopedia

Answer 11

c. Increased ammonia load in the liver The accumulation of excess protein in the body could lead to a hypercatabolic state and an increase in protein breakdown. As a result, this could lead to a high nitrogen turnover that increases ammonia load to the liver. Reference: Doc Jan Monzon’s Lecture on Protein Breakdown, Nitrogen Turnover, & Urea Cycle.

Answer 12

a. Dihydroxyacetone phosphate Glycerol can be phosphorylated by glycerol kinase (which uses ATP) to form glycerol-3-phosphate, which can in turn enter the gluconeogenic pathway via oxidation to DHAP. DHAP, however, is a glycolysis intermediate, not glycerol-3-phosphate (should not be confused with glyceraldehyde-3-phosphate) Succinyl-CoA, on the other hand, is the glycolysis entry point for propionate, which is a minor noncarbohydrate source of carbons for gluconeogenesis in humans. Pyruvate, is the glycolysis entry point for lactate (via lactate dehydrogenase in the presence of NAD+) and glucogenic amino acids like alanine (via transamination reactions involving a-ketoglutarate) Reference: Batch 2023 Biochemistry Evals 4 ratio on Carbohydrate Metabolism.

Answer 13

d. Inactivation of pyruvate kinase Pyruvate kinase is the enzyme involved in the last step of glycolysis, converting PEP to pyruvate. If it is not inactivated, all the PEP that was synthesized during gluconeogenesis will just get reconverted back to pyruvate, causing a net loss of energy. Reference: Batch 2023 Biochemistry Evals 4 ratio on Carbohydrate Metabolism.

Answer 14

c. serotonin stores from increased melatonin production “People with SAD may also have difficulty with overproduction of melatonin. Melatonin is a hormone produced by the pineal gland that responds to darkness by causing sleepiness. As winter days become darker, melatonin production increases and, in response, those with SAD feel sleepy and lethargic.” Since melatonin is derived from serotonin, increased production of melatonin would mean that a decrease in serotonin stores is expected. Reference: Melrose S. (2015). Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches. Depression research and treatment, 2015, 178564. https://doi.org/10.1155/2015/178564

Answer 15

a. Glycolysis and amino acid synthesis Glycolysis is dominant in the fed state in which glucose is abundant. Most amino acids are deaminated to produce alpha keto acids. In a fed state, alpha keto acids can be used to synthesize triacylglycerol. Reference: Harper’s Illustrated Biochemistry. 13th Edition Doc Jan Monzon’s Powerpoint

Answer 16

b. Common bile duct Bile secretion: Right hepatic duct + Left hepatic duct = Common hepatic duct + Cystic duct = Common Bile Duct Reference: Batch 2024 Trans of Liver, HBT and Gallbladder

Answer 17

a. Supply pentoses and NADPH PPP provides a way for cells to oxidize glucose to generate NADPH and provides a way to synthesize pentose sugars. References: Doc VH’s handout

Answer 18

d. Glucose 6-phosphate dehydrogenase G6PD is the first step of PPP. It is rate-limiting and is regulated allosterically and feedback inhibited by NADPH. References: Doc VH’s handout

Answer 19

c. Pyruvic acid Reference: Batch 2022 Biochemistry Evals 5 ratio on Carbohydrate Metabolism.

Answer 20

b. Build up of Free Radicals Most commonly deficiency of Selenium - Accelerated atherosclerosis (bec enzymes mentioned help clear free radicals, if a lot of free radical induced damage to blood vessels) - Lead to heart attack, aneurysm, arterial occlusive disease, gangrene References: Doc Jan Monzon’s PPT and Batch 2024 Trans

Answer 21

b. Vitamins, B1, B2 and B3 B Vitamins are critical for amino acid metabolism and can become depleted when you take high doses of the BCAAs. BCAA metabolism requires Thiamin (B1), Riboflavin (B2), Niacin (B3), and Pantothenic acid (B5). These enzymes are limiting factors in BCAA metabolism. if there is megadosing BCAAs during training, it will eventually be affected. References: Poliquin. (2015). Pros and Cons of BCAA supplements. Retrieved form: https://main.poliquingroup.com/ArticlesMultimedia/Articles/Article/1394/The_Pros_Cons_of_BCAA_Supplements.aspx

Answer 22

a. Hexokinase The processes that usually follow after a meal (or entering the FED state) relate to the breakdown or usage of glucose, e.g., glycolysis or glycogenesis. These pathways in muscle tissue begin with a transfer of a phosphate group from ATP to a glucose molecule that has just entered the cell. This irreversible reaction produces glucose-6-P, which commits it to metabolism, because the product glucose-6-P cannot leave the cell anymore. An inhibitor of hexokinase is the product it forms, which is glucose-6-P, which makes sense. If glucose-6-P is being produced but does not enter glycolysis or another pathway, it accumulates and can decrease the activity of hexokinase so there is no overproduction of glucose-6-P General rule of thumb: Most enzymes are inhibited by their products or the final products of the entire pathway. References: Mark’s Basic Medical Biochemistry, 4th ed.

Answer 23

d. Glucose-6-phosphatase → glucose During fasting, two mechanisms that the liver can execute are: glycogenolysis and gluconeogenesis The production of glucose from gluconeogenesis (Greek: gluco, glucose; neo, new; genesis,creation) requires an enzyme in the last step, which is glucose-6-phosphatase. This is related to the first reaction of glycolysis as seen in no. 46, where we commit glucose into entering metabolism by adding a phosphate group to it. However, take note that although it looks like the reverse of hexokinase / glucokinase, it is not the reverse of it. (It is not the reverse because in glucose-6-phosphatase, ATP is not generated in this step) References: Mark’s Basic Medical Biochemistry, 4th ed.

Answer 24

c. pathologic positive nitrogen balance. Positive balance means more nitrogen is retained. under positive there are 2 types: Physiologic: pregnancy and puberty (growth spurt) Pathologic: excretion is imparied in liver failure and renal failure Negative balance means more nitrogen is broken down. example of these are severe malnutrition, wasting (trauma, malignancy), post -operative cases, and hypercatabolic states References: Doc Jan Monzon’s PPT

Answer 25

e. Phosphoenolpyruvate In gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the decarboxylation and phosphorylation of oxaloacetate to phosphoenolpyruvate. References: Harpers Illustrated Biochemistry 31st Ed. p.173

Answer 26

c. Threonine Glycine, Proline ,and Lysine (an essential amino acid) are the 3 main amino acids composing collagen.If there is an extensive wound, extensive surgery requiring a lot of wound healing and a lot of collagen then there is also an increased demand of glycine and proline. Threonine is one of the essential amino acids, when this is broken down, it can yield glycine and since it is essential, the availability of this will affect glycine . Reference: Doc Jan Monzon’s Lecture on Biosynthesis of Non- Essential Amino Acids

Answer 27

b. The liver contains an isoenzyme of hexokinase, called glucokinase, which is especially important in the fed state. The liver, in keeping with the role as a monitor of blood - glucose levels, possess a specialized isozyme of hexokinase called glucokinase that is not inhibited by the glucose 6 - phosphate. Glucokinase phosphorylates glucose only when it is abundant because it has about 50 - fold affinity of glucose than does hexokinase. Reference: Berg, J.M., Tymoczko, J.L., Stryer, L. (2002).The Glycolytic Pathway is Tightly Controlled. Biochemistry (5th Ed.) Section 16. 2.3 .https://www.ncbi.nlm.nih.gov/books/NBK22395/

Answer 28

d. Anaerobic glycolysis During intense exercise, oxygen demands of skeletal muscles exceed oxygen supply; hence (1) oxidation of NADH in the ETC, and (2) ATP production by oxidative phosphorylation are inhibited. As such, the muscles rely on anaerobic glycolysis, and pyruvate is converted to lactate by lactate dehydrogenase as NADH is oxidized. This reaction generates NAD+ which allows glycolysis to proceed, and ATP is generated by substrate-level phosphorylation. Serum lactate level then becomes elevated causing a decrease in blood pH leading to metabolic acidosis. Reference: Batch 2023 Evals 04 Carbohydrate Metabolism.

Answer 29

c. Improved cholesterol levels Taurine, a special amino acid from cysteine, has potential metabolic benefits. It can reduce bad cholesterol (i.e., LDL and VLDL) by downregulating the hepatic production of apolipoprotein B100 needed by VLDL and LDL. Reference: Batch 2024 Trans 07 Specialized Products and Derivatives from Amino Acids, p. 3

Answer 30

a. There is increased alanine transported to the liver. “In the fasting state, there is a considerable output of alanine from skeletal muscle, far in excess of the amount in the muscle proteins that are being catabolized. It is formed by transamination of pyruvate produced by glycolysis of muscle glycogen, and is exported to the liver, where, after transami- nation back to pyruvate, it is a substrate for gluconeogenesis.” Reference: Harper's Illustrated Biochemistry (30th ed) Section IV Metabolism of Carbohydrates, pp. 190-191

Answer 31

a. Conversion of glycogen synthase to the active site. Epinephrine is a hormone/neurotransmitter that functions as the ‘fight-or-flight’ of a person. When this is released, the system will trigger the rapid degradation of glycogen because glucose is needed for energy production. Conversion of glycogen synthase will be counterproductive in this situation. References: Batch 2023 Evals 04 Carbohydrate Metabolism.

Answer 32

a. Phosphoenolpyruvate The enzyme enolase in the glycolytic pathway is needed for the conversion of 2-phosphoglycerate to high-energy molecule phosphoenolpyruvate (PEP). Poisoning this enzyme will fail to produce phosphoenolpyruvate (PEP) References: Batch 2023 Evals 04 Carbohydrate Metabolism and Doc VH’s lecture on Carbohydrate Metabolism.

Answer 33

c. C References: Doc Jan’s lecture video

Answer 34

d. Valine, Leucine, Isoleucine. Leu, Val, Phe, Ile, Met, Lys, Tyr, Thr, Trp, His - these AA belong to ketoanalogues. a. Arg, Glu, Asn - not included ketoanalogues b. Ala, Glu - not included in ketoanalogues c. Gly, Pro - not included in ketoanalogues References: Doc Jan’s lecture video

Answer 35

a. Both the oxidative and non-oxidative phase In cases such as fatty acid biosynthesis where more NADPH is needed than ribose 5-phosphate, both oxidative and non-oxidative phases are required. Oxidative phase produces NADPH while the non-oxidative phase converts ribulose 5-phosphate to glucose 6-phosphate to produce more NADPH. Reference: Marks’ Basic Medical Biochemistry 5th Ed.

Answer 36

d. ATP Conversion of glutamate to glutamine needs enzyme glutamine synthetase. Remember that synthetase reactions need ATP. Reference: Doc Jan Monzon’s PPT

Answer 37

d. Liberation of Iron As heme is broken down to bilirubin, the process directly yields CARBON MONOXIDE and liberates IRON for storage and future use. This process occurs with the presence of oxygen and NADPH. Thus, resulting in biliverdin which is further reduced by biliverdin reductase to ultimately converted to bilirubin. Conversion of heme to bilirubin by reticuloendothelial cells can be observed visually as the purple color of the heme in a hematoma slowly converts to the yellow pigment of bilirubin. Creation of bilirubin - incorrect; it is not directly produced. Reference: Harper’s Illustrated Biochemistry. 13th Edition Doc Jan Monzon’s Powerpoint

Answer 38

d. Vitamin B6 Glutamate collects the nitrogen from most amino acids except lysine, threonine, proline and hydroxyproline. It acts as the collector because it is the only amino acid that undergoes oxidative deamination at a rapid enough rate to clear the body from excess nitrogen. NOTE: Most if not all transamination reactions (transaminase enzyme) rely on pyridoxal phosphate (Vit B6) as coenzyme/ cofactor. › Transamination will not work if a person had Vit B6 deficiency › Clinical scenario: Patient undergoes tuberculosis therapy which requires isoniazid (Isoniazid depleted Vit B6) - result to difficulty in dealing with tuberculosis but also with nitrogen accumulation in the body because all these transamination processes will be LESS efficient. Reference: Doc Jan Monzon’s Lecture

Answer 39

a. A Serine is derived from 3-phosphoglycerate which is an intermediate in the glycolytic pathway. Since pyruvate is the final product of glycolysis in aerobic settings, the carbon skeleton of serine will ultimately end up to pyruvate. References: Doc Jan’s lecture video

Answer 40

a. Pancreatic tumor located in the pancreatic head Pancreatic tumor located in the pancreatic head results in an obstruction of the biliary tree. This leads to post-hepatic jaundice (aka obstructive jaundice) and explains the elevated direct/conjugated bilirubin of the patient. References: Doc Jan’s lecture video

Answer 41

b. Reduction of oxidized glutathione to protect against superoxides. In red blood cells the pentose phosphate pathway provides NADPH for the reduction of oxidized glutathione catalyzed by glutathione reductase, a flavoprotein containing FAD. Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione peroxidase, an enzyme that contains the selenium analogue of cysteine (selenocysteine) at the active site. References: Harper’s Illustrated Biochemistry. 28th Edition

Answer 42

d. He may develop severe joint paints later on. Alkaptonuria was first recognized and described in the 16th century. The defect is lack of homogentisate oxidase. The urine darkens on exposure to air due to oxidation of excreted homogentisate. Late in the disease, there is arthritis and connective tissue pigmentation (ochronosis) due to oxidation of homogentisate to benzoquinone acetate, which polymerizes and binds to connective tissue. Reference: Harper’s Illustrated Biochemistry. 28th Edition

Answer 43

d. Cytoplasm In this setting,of ischemia (oxygen-deprivation), the patient’s acidosis is likely due to lactic acid production under anaerobic conditions. Glycolysis is the biochemical pathway in which glucose is oxidized to pyruvate within the cytosol. In anaerobic conditions, pyruvate is converted into lactic acid by lactate dehydrogenase, an enzyme located in the cytoplasm. The other choices can be eliminated since pyruvate to lactic acid conversion under anaerobic condition does not happen because lactate dehydrogenase is not present in those regions. Reference: 2023 Trans (Rationalization of Doc VH)

Answer 44

a. All of the choices. On fatal arrythmias: Sinus tachycardia is the most common cardiac consequence of epileptic seizures and may occur in up to 80% of seizures. It may be associated with palpitations, but not with clinical signs such as syncope. Ictal asystole and rarer ictal arrhythmias have also been suggested as a potential pathomechanism for Sudden Unexpected Death in Epilepsy (SUDEP). References: Van der Lende M., Surges R., Sander J.W. (2016). Cardiac arrhythmias during or after epileptic seizures. Journal of Neurology, Neurosurgery & Psychiatry, 87, 69-74. On myoglobinuria: The typical clinical manifestations of Rhabdomyolysis (RM) are myalgia, muscle weakness, and myoglobinuria. Seizures as cause of RM are classified as belonging to the category of 'internal factors' that result from injury due to involuntary muscle overuse. One study that included 475 hospitalized RM patients found that seizures occurred in 32 (approximately 7%) patients, and was considered to subsequently result in RM. However, RM is more common in status epilepticus when compared with those having a single seizure attack. References: Zhou J., Luo B., & Peng G. (2017). A single seizure attack induced rhabdomyolysis. Neurol India, 65, Suppl S1, 93-4. On hyperkalemia: The most serious manifestations of hyperkalemia are muscle weakness or paralysis, cardiac conduction abnormalities, and cardiac arrhythmias. Unlike other electrolyte alterations, hypokalemia or hyperkalemia rarely causes symptoms in the CNS, and seizures do not occur. The majority of patients with mild hypokalemia are asymptomatic and initial symptoms, when they occur, may be non-specific such as weakness or fatigue. References: Baratloo, A., Rouhipour, A., Forouzanfar, M., Rahmati, F., & Hashemi, B. (2013). Hypokalemia-induced abnormal movements: case report. Trauma monthly, 18(3), 141–144. https://doi.org/10.5812/traumamon.12016

Answer 45

a. Succinate Dehydrogenase Succinate dehydrogenase is bound to the inner mitochondrial membrane and the only dehydrogenase who uses FAD as its electron acceptor The cofactor FAD is housed or built in one of the domains of succinate dehydrogenase, and its reducing equivalents get transferred from succinate on to FAD to form FADH2, succinate being converted to fumarate in the process. Reference: Doc VH lectures and batch 2023 rationalization by Doc VH

Answer 46

a. 2-Oxogluterate 2-Oxoglutarate or 𝛂-Ketoglutarate directly forms the amino acid Glutamate via the enzyme glutamate dehydrogenase. This process includes the removal of a ketone group, and replacing it with an amino group, after doing so, addition of an amino group will help to form it into a new amino acid via transamiantion. Reference: Doc VH lectures and batch 2023 rationalization by Doc VH

Answer 47

a. Porphyria cutanea tarda Porphyria cutanea tarda (PCT) classic presentation is that of blistering or vesicles becoming tense bullae on photosensitive fragile skin which then rupture leaving the skin with a slow-healing erosions and crusted lesions. PCT is associated with a reduction in hepatic uroporphyrinogen decarboxylase. A reduced enzyme-substrate affinity leads to an accumulation of porphyrinogens in the skin and tissues resulting in photosensitivity (spontaneous oxidation of porphyrinogens to porphyrins). Reference: Doc Jan Monzon’s PPT - Heme Metabolism

Answer 48

c. Tumors of the adrenal medulla Tyrosine is the precursor for: - catecholamine - thyroid hormones - melanin Some tumors produce abnormal levels of catecholamines. Reference: Doc Jan Monzon’s PPT - Biosynthesis of Nonessential Amino Acids

Answer 49

d. The glucosyl residue directly attached to glycogenin is nonreducing.. Only one glucosyl residue that has an anomeric carbon not linked in the glycosidic bond. found at the very beginning of the chain attached to a protein called GLYCOGENIN. All the other ends of the chain in the glycogen molecule DO NOT HAVE free anomeric carbons =NONREDUCING ENDS Glycogenin- protein that begins the production of a glycogen molecule Reference: Doc Jan Monzon’s PPT

Answer 50

c. Acetoacetate Acetoacetate is an intermediate in Ketogenesis. When HMG-CoA has entered the mitochondria it undergoes reaction via the enzyme HMG-CoA Lyase and one Acetyl-CoA will be removed again and in the process it will produce Acetoacetate. Acetoacetate – is one of the ketone bodies and can undergo spontaneous degradation to form Acetone. Reference: Doc VH lectures and batch 2023 rationalization by Doc VH

Answer 51

a. Protein phosphatase Insulin activates tyrosine kinase receptors resulting in the phosphorylation and activation of protein kinase, followed by the protein phosphatase. The activated protein phosphatase will inactivate protein kinase and glycogen synthase, and activate glycogen synthase by removing the phosphate group. Reference: Harper’s Illustrated Biochemistry (30th edition)

Answer 52

c. The patient has decreased lean muscle mass. Urea and creatinine are excreted in urine; their serum concentrations can be used as markers of renal function because the serum concentration increases as renal function deteriorates.(p.566) Creatinine excretion is reasonably constant from day to day for any one individual, but varies between individuals because it depends mainly on muscle mass; creatinine is formed non-enzymically from creatine and creatine phosphate, most of which is in skeletal muscle (p.563). Reference: Harper's Illustrated Biochemistry (31st ed.)

Answer 53

b. Pyruvate dehydrogenase Pyruvate dehydrogenase is inhibited by its products, acetyl-CoA, and NADH. It is also regulated by phosphorylation (catalyzed by a kinase) of three serine residues on the pyruvate dehydrogenase component of the multienzyme complex, resulting in decreased activity and by dephosphorylation (catalyzed by a phosphatase) that causes an increase in activity. Reference: Harper’s Illustrated Biochemistry (30th ed) Chapter 17, Page 173

Answer 54

c. These cycles are used to convert malate to oxaloacetate and then to aspartate, at the same time reducing NAD+ to NADH for the electron transport chain. This reaction refers to the Krebs cycle or the Citric Acid Cycle where malate is oxidized to oxaloacetate by malate dehydrogenase, which is linked to NAD+ reduction. Reference: Harper’s Illustrated Biochemistry: Chapter 16, pp 153

Answer 55

b. Cysteine PAPS or 3’-phospho-adenosine-5’-phosphosulfate is a key by-product of cysteine metabolism which is an active sulfate. This is needed for the transfer of sulfate to the sugars of glycosphingolipid molecules and the sulfated glycosaminoglycans (e.g. heparan sulfate, chondroitin sulfate, keratan sulfate, dermatan sulfate). Reference: Batch 2024, Module 10B, Trans 06 Protein Metabolism: Fate of Carbon Skeleton p.5.

Answer 56

b. Debrancher enzyme The function of the debrancher or debranching enzyme is an important step in the mobilization or breakdown of glycogen stores. The process includes the ceasing of phosphorylase to cleave α-1,4-glycosidic linkages four glucosyl residues from an α-1,6-branch site. It has two catalytic activities: a transferase activity and a glucosidase which results in the release of free glucose. Reference: Case Files Biochemistry Lange (2nd Ed) Page 182

Answer 57

d. Activation of protein kinase A, through the adenylate cyclase pathway, and phosphorylation of PFK-2 During the fed state, there is an abundance of glucose, which eventually leads to an abundance of fructose 6-phosphate, as stated in the question. This intermediate allosterically activates the kinase function of PFK-2 (and inhibits its bisphosphatase function at the same time). PFK-2 then converts fructose 6-phosphate to fructose 2,6-bisphosphate, an intermediate that allosterically activates PFK-1 and inhibits fructose 1,6-bisphosphatase, consequently leading glucose down the pathway of glycolysis. Reference: Batch 23 Ratio

Answer 58

a. Transport of bilirubin to the liver Bilirubin is transported to the liver bound to serum albumin. Patients with decreased protein levels (in this case, protein-losing enteropathy) tend to have decreased albumin levels as well. As a consequence, of low albumin levels, decreased amounts of bilirubin (B1) are transported to the liver and the rest remains in the blood which will then cause Jaundice. Reference: Doc Jan Monzon’s Lecture and Heme Metabolism PPT.

Answer 59

d. Gluconeogenesis The viral infection causes liver cells damage causing AST and ALT to leak out of the cell to the bloodstream, making them not available to be utilized in the gluconeogenesis in the liver. AST- is involved in converting glutamate to oxaloacetate which is both an intermediate in TCA and Gluconeogenesis. ALT- converts alanine to pyruvate, which is used in gluconeogenesis during the fasted state. Reference: Doc Monzon’s Lecture video and Batch 2024’s Protein Metabolism trans (Part 1 & 3)

Answer 60

d. NADH : NAD+ Alcohol metabolism favors an increase in NADH to NAD+ ratio which is true in a drinking binge. The abundance of NADH favors the reduction of pyruvate to lactate. The ethanol mediated increase in NADH causes the gluconeogenic precursors to be diverted into alternate pathways resulting in the decrease in the synthesis in glucose. It is common in alcoholics and among those who binge drink to not eat anything nutritive, and thus they have depleted liver glycogen stores. The gluconeogenesis will be impaired, metabolism of ethanol in such circumstances can precipitate HYPOGLYCEMIA which can produce behaviors associated with alcohol intoxication such as agitation, impaired judgement and combativeness Pyruvate- is a substrate in gluconeogenesis Hypoglycemia- blood sugar is lower than normal. Reference: Doc VH’s Lecture Video and Handout (Carbohydrate Metabolism Part III: Pentose Phosphate Pathway and Alternative Carbohydrate Metabolism Pathways) and Siopao (Batch 2024): PART 3

Answer 61

c. Inferior mesenteric vein Distribution of ammonia production are as follows: intestine (mostly from colon) - 50%; kidney - 40%; RBCs - 5% and muscles - 5%. From the figure above, ammonia & ammonium ions are produced in the left half of the transverse colon, splenic flexure & descending colon. These parts of the colon initially drains into the left colic vein which is a tributary of the inferior mesenteric vein. Reference: Chapter 14. ammonia and urea. Barrett K.E.(Ed.), (2014). Gastrointestinal Physiology, 2e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=691§ionid=45431415

Answer 62

a. GAPDH Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is the enzyme that catalyzes the sixth step of glycolysis. This reaction is the combination of GAPDH and an inorganic phosphate (Pi) that leads to the formation of 1,3-Biphosphoglycerate. Hexokinase - catalyzes the first step of glycolysis; used to convert glucose to glucose-6-phosphate Phosphoglycerate Mutase - catalyzes the eight step of glycolysis; used to form 3-Phosphoglycerate to 2-Phosphoglycerate Phosphofructokinase-1 (PFK-1) - catalyzes the third step of glycolysis; conversion of Fructose-6-phosphate to Fructose-1,6-bisphosphate; rate limiting step; first committed step of glycolysis; regulated enzyme Reference: Doc VH’s Lecture Video and Handout (Carbohydrate Metabolism Part I: Glycolysis and Gluconeogenesis)

Answer 63

c. Glutamine - essential for maintaining resting vascular tone. Catalyzed by nitric oxide synthase, Arginine is converted to l-ornithine and nitric oxide, an intracellular signaling molecule that serves as a neurotransmitter, smooth muscle relaxant, and vasodilator. Nitric Oxide - The major vasodilator that maintains vascular tone, alongside other dilators and constrictor substances. Reference: Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2018). Harper's illustrated biochemistry (31st ed., p. 308). New York: Mcgraw-Hill Education.

Answer 64

c. It is a large, highly branched heteropolysaccharides. The reason why the Glycogen was designed to be branched is for its rapid degradation and rapid synthesis. It allows enzymes to work on several chains simultaneously from the multiple nonreducing ends, therefore resulting in a large amount of glucose-1 phosphate released in a short period of time. Reference: Doc VH’s lecture

Answer 65

c. Acetyl-CoA Ethanol to Acetyl-CoA 1st step: Ethanol is first oxidized in the liver to acetaldehyde by cytosolic alcohol dehydrogenase. 2nd step: Acetaldehyde is further oxidized to acetate by mitochondrial acetaldehyde dehydrogenase 3rd step: Much of the acetate produced from ethanol leaves the liver to blood stream to muscle, where it is converted to ACETYL-COA, which can be used to provide energy via the Krebs cycle Acetyl-CoA may also be formed in the liver and used as a precursor for lipid biosynthesis. Acetyl-CoA- is an oxidized by series of enzymes that make up the cyclical series of reactions called the Krebs Cycle Reference: Doc VH’s Lecture Video and Handout (Carbohydrate Metabolism Part III: Pentose Phosphate Pathway and Alternative Carbohydrate Metabolism Pathways )

Answer 66

b. Ribose-5-phosphate can be recycled back to glucose-6-phosphate via the non-oxidative phase to produce more NADPH via the oxidative phase Reference: Lieberman, M., Peet, A., & Chansky, M. (2018). Pathways of Sugar Metabolism: Pentose Phosphate Pathway, Fructose, and Galactose Metabolism. In Marks' basic medical biochemistry: A clinical approach (4th ed., p. 535. 539). Philadelphia: Wolters Kluwer.

Answer 67

a. Production of gastric acid. b. Biliverdin, a product of heme catabolism, is an antioxidant and as such performs a significant role when heme oxygenase is induced by stress. (Devlin, 2011, p. 798) c. At least half of the common drugs that we ingest are metabolized by isoforms of cytochrome P450. (Rodwell et al., 2018, p. 557) d. Heme proteins are ubiquitous in biology and serve diverse functions, including oxygen transport and storage (e.g. hemoglobin and myoglobin). (Rodwell et al., 2018, p. 305) References: Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2018). Harper’s Illustrated Biochemistry (31st ed.). McGraw Hill Education. Devlin, T. M. (2011). Textbook of Biochemistry with Clinical Correlations (7th ed.). John Wiley & Sons, Inc.

Answer 68

a. GAP and fructose-6-P. Reference: Van Haute, M. Q. (2021). Carbohydrate Metabolism 3a: Pentose Phosphate Pathway

Answer 69

d. Aldehyde dehydrogenase. Deficiency in aldehyde dehydrogenase results in the accumulation of acetaldehyde, which is produced from the metabolism of alcohol by alcohol dehydrogenase. Reference: Doc VH’s lecture

Answer 70

b. Kidney. a. RBC is not an organ. c. Functions as a blood filter and the graveyard of erythrocytes. It is not involved in gluconeogenesis. d. Gluconeogenesis occurs mainly in the liver under fasting conditions. Under extreme conditions of starvation, gluconeogenesis can also occur in the renal cortex Reference: Doc VH’s lecture

Answer 71

a. Under anaerobic conditions, pyruvate does not form because glycolysis does not occur. Under anaerobic conditions, glycolysis still occurs and pyruvate is still formed, but instead of being converted into acetyl-CoA to enter TCA (which can’t proceed), it is converted to lactate by the enzyme lactate dehydrogenase. Reference: Carbohydrate Metabolism Part 1 2024 Trans

Answer 72

b. Biotin and cobalamin The Methionine pathway shared with Valine, Isoleucine and others will lead to Propionyl-CoA. Propionyl-CoA will become Succinyl-CoA to enter the TCA cycle. In the TCA cycle leading up to oxaloacetate, this can enter gluconeogenesis, making Methionine a glucogenic amino acid. Vitamins required for methionine are biotin and cobalamin aka Vitamin B12. Reference: Protein Metabolism Part 3 2024 Trans

Answer 73

d. Pyruvate Dehydrogenase Many Alcoholics are thiamine deficient (both because of poor diet and also because alcohol inhibits thiamine absorption. Pyruvate dehydrogenase is inhibited leading to the accumulation of pyruvate. Thus, these metabolic defects cause neurological disturbances as shown by the patient’s symptoms. Reference: Harpers Illustrated Biochemistry 31st ed. Chapter 17: Glycolysis & the Oxidation of Pyruvate,Page 163

Answer 74

d. Undergo Mitosis Glycine gives off one of its carbon to purines which is essential in DNA and RNA synthesis. Reference: Doc Jan’s Video Lecture Protein Metabolism Part 3

Answer 75

a. Isocitrate dehydrogenase. Reference: Doc VH’s lecture

Answer 76

d. Oxidized glutathione. Oxidized Glutathione accumulates because of G6PD deficiency. The pentose phosphate pathway in RBCs maintains glutathione in a reduced state. Glucose-6-phosphate dehydrogenase (G6PD) is required to catalyze nicotinamide adenine dinucleotide phosphate (NADP) to its reduced form (NADPH). In patients with G6PD Deficiency, during oxidative stress ther is a build-up of NADP, and NADPH levels are too low to maintain glutathione in a reduced state. As a result of lowered levels of reduced glutathione, there is a build-up of oxidants, which damages hemoglobin as well as enzymes. The affected RBCs are ultimately removed from circulation by the spleen causing anemia. Reference: Doc VH’s lecture

Answer 77

a. Proline Proline synthesis and catabolism is via the pathway of ornithine and glutamate, the latter two amino acids serve as its immediate precursors as well as metabolites. Ornithine is one of the intermediates for urea cycle, and glutamate is metabolically connected to tricarboxylic acid (TCA) cycle, the major cycle for energy production. It is hypothesized that the significantly increased rates of net nitrogen loss and energy "production", as the consequence of the accelerated activities of both the urea and TCA cycles in burn injury "drain" both ornithine and glutamate, thus depleting tissues of the availability of proline. Hence, the de novo synthesis of proline is likely to be affected by the reduced availability of its major precursors: glutamate and ornithine. This hypothesis is supported by 1) tissue and circulating glutamine content are reduced in stressed conditions; 2) ornithine disposal via oxidation is significantly increased after burn injury(2). Therefore, the availability of proline is likely to be limiting after burn injury for the synthesis of proteins. On the other hand, proline requirement is significantly increased in burn patients due to the high demand for tissue repair and wound healing. As a result, providing an adequate proportion of its precursors, glutamine / glutamate and / or as performed proline, is of importance to maintain the appropriate supply and balance of amino acids for protein and other synthetic functions after burn injury. References: https://clinicaltrials.gov/ct2/show/NCT00216983

Answer 78

d. 30 to 32 Reference: Doc VH’s lecture video

Answer 79

d. 3 to 5 ATP molecules The number of ATP molecules derived from each NADH molecule generated via glycolysis depends on the shuttle that transports the NADH (or more accurately, the reducing equivalents it carries) from the mitochondria across the inner mitochondrial membrane into the mitochondrial matrix (recall that glycolysis occurs in the cytoplasm). If the malate-aspartate shuttle is used, 2.5 molecules of ATP per NADH will be generated because NADH is the cofactor accepting the reducing equivalents in the matrix side. On the other hand, if the glycerophosphate pathway is used, only 1.5 molecules of ATP per NADH will be generated since the receiving cofactor in the matrix side is FAD. Reference: Doc VH’s lecture video

Answer 80

b. Glutamine References: Garcia-Bermudez, J., Williams, R., Guarecuco, R., & Birsoy, K. (2020). Targeting extracellular nutrient dependencies of cancer cells. Molecular Metabolism, 33, 67-82. doi: 10.1016/j.molmet.2019.11.011

Answer 81

d. NADH and FADH2 The electron carriers produced (NADH and FADH2) cannot provide energy to cellular processes directly. Instead, the processes of the electron transport chain and oxidative phosphorylation will use the energy from these molecules to activate the enzyme complex ATP synthase, which produces ATP. The role of NADH and FADH2 is to donate electrons to the electron transport chain. They both donate electrons by providing an hydrogen molecule to the oxygen molecule to create water during the electron transport chain. NADH is a product of both the glycolysis and Kreb cycle. FADH2 is only produced in Krebs cycle. Reference: Molnar, C., & Gair, J. (2015). Concepts of Biology - 1st Canadian Edition. Bccampus. Retrieved from https://opentextbc.ca/biology/

Answer 82

a. Aldose reductase Diabetic cataract results from osmolysis due to sorbitol accumulation. The rise of glucose concentration in insulin insensitive tissues (peripheral nerves, renal glomeruli, seminal vesicles, and lens) increases the activity of the sorbitol pathway, which is responsible for the conversion of glucose to fructose. Glucose is reduced to sorbitol by aldose reductase, which cannot diffuse through cell membranes and remains trapped inside the cell. The accumulation of sorbitol inside the cell causes strong osmotic influx of water, resulting in swelling of the cell. Reference: Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2018). Harper's illustrated biochemistry (31st ed., pp. 190-191). New York: Mcgraw-Hill Education.

Answer 83

c. The high Km and high Vmax of glucokinase Glucokinase has high Km (low affinity) and high Vmax, while hexokinase has low Km (high affinity) and low Vmax. Source: Doc Van Haute’s Video lecture - Carbohydrate Metabolism

Answer 84

a. The rate-limiting step of gluconeogenesis is affected, resulting in a patient’s hypoglycemia With biotin deficiency as a result of ingesting an excessive amount of raw egg whites, the activity of the gluconeogenic enzyme pyruvate carboxylase, which is biotin-dependent, is impaired. As a result, oxaloacetate is not produced from pyruvate. Besides gluconeogenesis not proceeding as it is supposed to, replenishment of oxaloacetate needed for the Krebs cycle is likewise impaired (pyruvate carboxylase catalyzes the main anaplerotic reaction). Since a protein-only diet is another condition that makes gluconeogenesis favorable besides fasting/starvation, his raw egg white-only diet contributed to his condition (and may have worsened it since he cannot utilize the protein he ingested anyway on account of pyruvate carboxylase being inactive in light of his biotin deficiency). The pyruvate carboxylase step, however, is NOT the rate-limiting step of gluconeogenesis; the PEPCK step is. Reference: Dr. VH’ Lecture on Carbohydrate Metabolism: Gluconeogenesis

Answer 85

d. Arginine Arginine is another important amino acid because it stimulates T lymphocytes, augments natural killer cell performance, and accelerates nitric oxide synthesis, which improves resistance to infection Source: Clark, A., Imran, J., Madni, T., & Wolf, S. E. (2017). Nutrition and metabolism in burn patients. Burns & Trauma, 5. doi:10.1186/s41038-017-0076-x

Answer 86

b. decreased GABA GABA is an inhibitory neurotransmitter. It requires Glutamate for its synthesis. Since the patient has been diagnosed of liver cirrhosis due to long-term alcoholism, glutamate in the CNS is then sequestered to form glutamine to clear out ammonia. The decreases in GABA formation will then lead to seizures. Reference: Doc Jan’s video lecture on Protein Breakdown, Nitrogen Turnover, and Urea Cycle

Answer 87

a. Phosphoglycerate from Glycolysis. Oxidation of the α-hydroxyl group of the glycolytic intermediate 3-phosphoglycerate, catalyzed by 3-phosphoglycerate dehydrogenase, converts it to 3-phosphohydroxypyruvate. Transamination and subsequent dephosphorylation then form serine (Figure 27-7). Following conversion of methionine to homocysteine, homocysteine and serine form cystathionine, whose hydrolysis forms cysteine and homoserine (Figure 27-11). Reference: Harper’s Illustrated Biochemistry 29th ed.

Answer 88

b. Muscle glycogen phosphorylase The symptoms described suggest a diagnosis of McArdle disease, a type V glycogen storage disorder caused by a lack of muscle glycogen phosphorylase (or myophosphorylase). This enzyme breaks down muscle glycogen by removing the a-1,4 glucosyl units from the outer branches of glycogen. In healthy individuals, the glucose-1-phosphate liberated by the phosphorylase is converted to glucose-6-phosphate and oxidized to pyruvate via glycolysis. Muscle pyruvate can be converted to lactate and released into the blood but most of it crosses into the mitochondria where it is used to generate ATP by oxidative phosphorylation. As a consequence of the myophosphorylase deficiency, patients with McArdle disease are unable to obtain energy from muscle glycogen stores. The abnormal accumulation of glycogen in muscle tissue leads to painful cramps and myoglobinuria during strenuous exercise, with no increase in lactic acid in the blood as would normally be seen. Reference: Principles of Biochemistry, 7th Edition by Albert Lehninger

Answer 89

c. Alkaline phosphatase Elevations of ALP are of most diagnostic significance in the evaluation of hepatobiliary and bone disorders. In hepatobiliary disorders, elevations are more predominant in obstructive conditions than in hepatocellular disorders. In biliary tract obstruction, ALP levels range from 3 to 10 times the ULN. Increases are primarily a result of increased synthesis of the enzyme induced by cholestasis. Reference: Clinical Chemistry Principles, Techniques, and Correlations, 7th Edition by Bishop et al.

Answer 90

b. d (Succinyl-CoA) Catabolism of branched chain amino acids (Leucine, Isoleucine, and Valine) is a multistep process catalyzed by the branched chain ketoacid dehydrogenase complex. The final product of Valine is propionyl CoA, which is then converted to succinyl CoA, which enters the Kreb’s cycle. Reference: Doc Jan Monzon’s lecture and PPT- Protein and Amino Acid Metabolism Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2018). Harper's illustrated biochemistry (31st ed., p.281). New York: Mcgraw-Hill Education.

Answer 91

b. 20 | Reference: Harper’s Illustrated Biochemistry 29th ed.

Answer 92

b. GAP to 1,3-BPG In the Glycolysis, only GAP requires NAD+ to become 1,3-BPG. Reference: Dr. Van Haute’s Lecture on Carbohydrate Metabolism: Glycolysis

Answer 93

a. Liver and muscles. Branched Chain Amino Acids (BCAA) Valine and isoleucine are stored in the liver and significant on the skeletal muscles. Recent studies revealed that these BCAA are administered for treatment of advanced liver disease. Valine and Isoleucine form a significant of the flux between liver and muscles. Reference: Doc Jan’s video lecture

Answer 94

b. Aspartate Aspartate is converted into oxaloacetate by a reaction catalyzed by the enzyme aspartate aminotransferase, which transfers an amino group from aspartate to 2-oxoglutarate to produce glutamate and oxaloacetate. Source: Doc Jan’s PPT on Metabolism of Proteins and Amino Acids Part 1

Answer 95

d. 2 NAD+ molecules 2 NAD+ - used at the 6th step of glycolysis yielding 2 NADH 2 ATP molecules - 1 ATP is used at the 1st and 3rd step while 2 ATPs are produced at the 7th and 10th step, yielding 2 ATP molecules 2 pyruvate - produced at the 10th step of glycolysis Reference: Doc VH’s lecture video - Carbohydrate Metabolism (Glycolysis)

Answer 96

c. glycosaminoglycans Glycosaminoglycans (GAGs) are made up of disaccharide repeating units. This disaccharide unit is composed of an amino sugar (hexosamine) and a uronic acid. Reference: Doc VH’s lecture on Alternative Metabolic Pathways

Module 10 Part 1 Flashcards

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