Alt Pathways to Carbohydrate Metabolism

Question 1 What are the two phases of the pentose phosphate pathway?

Oxidative phase and non-oxidative phase.

Question 2 Which phase of the pentose phosphate pathway is irreversible?

The oxidative phase.

Question 3 How many NADPH are produced per glucose-6-phosphate in the oxidative phase of the PPP?

2 NADPH.

Question 4 Which enzyme catalyzes the first step of the pentose phosphate pathway?

Glucose-6-phosphate dehydrogenase (G6PD).

Question 5 What is the only source of NADPH in red blood cells according to the lecture?

The pentose phosphate pathway.

Question 6 Why is NADPH essential in RBCs?

It maintains glutathione in the reduced form to protect RBCs against oxidative damage.

Question 7 What enzyme of the non-oxidative PPP requires thiamine pyrophosphate?

Transketolase.

Question 8 What syndrome can result from severe thiamine deficiency impairing transketolase activity?

Wernicke-Korsakoff syndrome.

Question 9 Why does G6PD deficiency cause hemolytic anemia?

RBCs cannot generate enough NADPH to maintain reduced glutathione and detoxify oxidizing agents.

Question 10 What hemoglobin inclusion can form in G6PD deficiency?

Heinz bodies.

Question 11 What are the major precipitating factors of hemolysis in G6PD deficiency?

Oxidant drugs, fava beans, and infection.

Question 12 Which antimalarial drug is a classic trigger of hemolysis in G6PD deficiency according to the lecture?

Primaquine.

Question 13 What pathway converts glucose to glucuronic acid and provides UDP-glucuronate for conjugation?

The uronic acid pathway.

Question 14 What is the active form of glucuronic acid used for glucuronidation?

UDP-glucuronate.

Question 15 What enzyme is severely deficient in Crigler-Najjar syndrome according to the lecture?

UGT1A1.

Question 16 What bilirubin abnormality occurs in Crigler-Najjar syndrome?

Unconjugated hyperbilirubinemia.

Question 17 What enzyme deficiency causes hereditary fructose intolerance?

Aldolase B deficiency.

Question 18 What metabolite accumulates in hereditary fructose intolerance?

Fructose-1-phosphate.

Question 19 What major acute metabolic effect results from fructose-1-phosphate accumulation in HFI?

Severe hypoglycemia after fructose ingestion.

Question 20 What is the treatment of hereditary fructose intolerance?

Eliminate fructose, sucrose, and sorbitol from the diet.

Question 21 What enzyme deficiency causes essential fructosuria?

Fructokinase deficiency.

Question 22 What is the clinical presentation of essential fructosuria?

It is benign and usually asymptomatic.

Question 23 What enzyme deficiency causes classic galactosemia?

Galactose-1-phosphate uridylyltransferase (GALT) deficiency.

Question 24 What neonatal infection is specifically associated with classic galactosemia?

E. coli sepsis.

Question 25 What enzyme deficiency causes the mild galactose disorder associated mainly with childhood cataracts?

Galactokinase deficiency.

Question 26 What causes cataracts in galactokinase deficiency?

Galactitol accumulation through aldose reductase causing osmotic damage.

Question 27 What is the two-step sequence of the polyol pathway?

Glucose -> sorbitol by aldose reductase, then sorbitol -> fructose by sorbitol dehydrogenase.

Question 28 Which cofactor is consumed when aldose reductase converts glucose to sorbitol?

NADPH.

Question 29 Why does hyperglycemia increase oxidative stress through the polyol pathway?

Aldose reductase consumes NADPH, impairing glutathione regeneration.

Question 30 What major diabetic complications are linked to polyol-pathway activation?

Cataract, retinopathy, nephropathy, and neuropathy.

Question 31 What enzyme is deficient in Von Gierke disease according to the lecture?

Glucose-6-phosphatase.

Question 32 What two classic findings of Von Gierke disease are listed?

Hypoglycemia and hepatomegaly.

Question 33 What is the effect of NADPH on G6PD according to the lecture?

NADPH is a potent inhibitor of G6PD.

Question 34 What hormone upregulates G6PD?

Insulin.

Question 35 What does transketolase transfer?

A two-carbon fragment from a ketose to an aldose.

Question 36 What does transaldolase transfer?

A three-carbon fragment.

Question 37 What classic hemolytic disorder results from deficiency of glucose-6-phosphate dehydrogenase?

G6PD deficiency.

Question 38 Which antibiotic class is a classic trigger of hemolysis in G6PD deficiency?

Sulfonamides or sulfa drugs.

Question 39 Does the uronic acid pathway generate ATP?

No.

Question 40 Which enzyme converts UDP-glucose to UDP-glucuronate?

UDP-glucose dehydrogenase.

Question 41 Which enzyme family catalyzes glucuronidation reactions?

UDP-glucuronosyltransferase (UGT) enzymes.

Question 42 What is another name for the pentose phosphate pathway?

Hexose monophosphate shunt (HMP) or phosphogluconate pathway.

Question 43 What are the major uses of the pentose phosphate pathway listed in the lecture?

Fatty acid synthesis, steroid synthesis, reduction of glutathione, and nucleotide/nucleic acid formation.

Question 44 How many irreversible reactions are in the oxidative phase of the PPP?

Three.

Question 45 Which tissues are emphasized as important sites of the oxidative PPP for reductive biosynthesis?

Liver, lactating mammary gland, adipose tissue, testes, ovaries, placenta, and adrenal cortex.

Question 46 Which blood cell type is emphasized as especially dependent on the PPP?

Red blood cells.

Question 47 What sugar phosphate is the major pentose product emphasized from the PPP?

Ribose-5-phosphate.

Question 48 What is ribose-5-phosphate used for?

Synthesis of RNA, DNA, and other coenzymes, especially in rapidly dividing cells.

Question 49 What is the role of NADPH in fatty acid and steroid synthesis?

It provides reducing power for reductive biosynthesis.

Question 50 What is the role of NADPH in glutathione metabolism?

It keeps glutathione reduced so it can counter damaging oxygen radicals.

Question 51 What cytochrome system requires NADPH according to the lecture?

Cytochrome P450 monooxygenase system.

Question 52 What role does NADPH play in white blood cells?

It supports phagocytosis and microbe killing.

Question 53 What signaling molecule synthesis requires NADPH according to the lecture?

Nitric oxide synthesis.

Question 54 What are reactive oxygen species?

Reactive by-products of aerobic metabolism that can cause chemical damage.

Question 55 What cellular components can ROS damage according to the lecture?

DNA, proteins, and unsaturated lipids.

Question 56 Which sex is stated to be affected more commonly by G6PD deficiency?

Males.

Question 57 Why is G6PD deficiency most severe in erythrocytes?

The PPP is their only source of NADPH, and RBCs lack nuclei and ribosomes.

Question 58 What happens to glutathione in G6PD deficiency?

Reduced glutathione is not adequately maintained.

Question 59 What hemoglobin change leads to Heinz-body formation in G6PD deficiency?

Oxidation of sulfhydryl groups in hemoglobin.

Question 60 What malaria organism may G6PD deficiency provide some protection against according to the lecture?

Plasmodium falciparum.

Question 61 What symptoms are listed during G6PD-deficient hemolytic episodes?

Jaundice, dark urine, fatigue, and back pain.

Question 62 What substance in fava beans is stated to generate ROS?

Vicine.

Question 63 Which drug categories are listed as oxidant triggers in G6PD deficiency?

Antibiotics, antimalarials, analgesics, and antipyretics.

Question 64 What are the main products of the uronic acid pathway listed in the lecture?

Glucuronic acid, galacturonic acid, and pentoses.

Question 65 What initial enzyme step does the uronic acid pathway share with the PPP?

Glucose-6-phosphate dehydrogenase.

Question 66 What is the main detoxification function of glucuronic acid?

Conjugation of compounds to increase water solubility for excretion.

Question 67 Which endogenous compounds are specifically mentioned as glucuronidation targets?

Bilirubin and steroid hormones.

Question 68 Which exogenous compounds are specifically mentioned as glucuronidation targets?

Drugs and xenobiotics.

Question 69 Why do humans require dietary vitamin C according to the uronic acid pathway discussion?

Humans cannot synthesize ascorbic acid through this pathway.

Question 70 What is essential pentosuria?

A benign autosomal recessive disorder causing urinary excretion of L-xylulose.

Question 71 What enzyme deficiency causes essential pentosuria according to the lecture?

L-xylulose reductase deficiency, also called xylulokinase in the lecture.

Question 72 Why can essential pentosuria be mistaken for diabetes?

It can produce a positive urine reducing-sugar test.

Question 73 In which population is essential pentosuria stated to be more common?

Ashkenazi Jewish populations.

Question 74 What causes alimentary pentosuria?

Consumption of large amounts of pentoses, such as pears.

Question 75 Which drugs are listed as causes of drug-induced pentosuria?

Barbital and chlorobutanol.

Question 76 What is glucuronic acid a precursor of?

Proteoglycans and conjugated glucuronides.

Question 77 What reaction produces UDP-glucuronate from UDP-glucose?

Oxidation of UDP-glucose at carbon 6 by UDP-glucose dehydrogenase.

Question 78 What cofactor is required by UDP-glucose dehydrogenase?

NAD+.

Question 79 What is the net reaction shown for UDP-glucuronate formation?

UDP-glucose + 2 NAD+ + H2O -> UDP-glucuronate + 2 NADH + 2 H+.

Question 80 What phase of detoxification uses glucuronidation?

Phase II detoxification.

Question 81 How does glucuronidation help eliminate bilirubin and drugs?

It makes them more water-soluble for biliary or renal excretion.

Question 82 Which common analgesic is specifically mentioned as undergoing glucuronidation?

Acetaminophen.

Question 83 What is Crigler-Najjar syndrome?

A severe UGT1A1 deficiency causing impaired bilirubin glucuronidation.

Question 84 What severe neurologic complication may result from Crigler-Najjar syndrome?

Kernicterus with potential brain damage.

Question 85 How does Crigler-Najjar type I differ from type II according to the lecture?

Type I is complete absence of activity, whereas type II is partial deficiency.

Question 86 What treatments are listed for Crigler-Najjar type I?

Phototherapy or liver transplantation.

Question 87 What is Gilbert syndrome?

A mild UGT1A1 deficiency causing benign unconjugated hyperbilirubinemia.

Question 88 What can exacerbate Gilbert syndrome?

Fasting or stress.

Question 89 What percentage of the population is stated to be affected by Gilbert syndrome?

About 5-10%.

Question 90 Why are glucuronidation defects clinically important?

They demonstrate the pathway's role in preventing toxicity from bilirubin accumulation.

Question 91 What are glycosaminoglycans?

Large negatively charged heteropolysaccharides.

Question 92 What structure is formed when GAGs are associated with protein?

Proteoglycans.

Question 93 What physical property of GAGs is emphasized in the lecture?

They bind large amounts of water.

Question 94 What extracellular-matrix role is attributed to GAGs?

They provide flexible support for the ECM.

Question 95 Name the common GAGs listed in the lecture.

Hyaluronate, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, and keratan sulfate.

Question 96 What cartilage proteoglycan is specifically mentioned in osteoarthritis?

Aggrecan.

Question 97 What happens when cartilage proteoglycans such as aggrecan degrade in osteoarthritis?

Joint-space narrowing and bone-spur formation.

Question 98 What is the bilirubin conjugation reaction shown in the lecture?

Bilirubin + 2 UDP-glucuronic acid -> bilirubin diglucuronide + 2 UDP.

Question 99 Which enzyme catalyzes bilirubin conjugation in the lecture?

UGT1A1.

Question 100 What are the major dietary sources of fructose listed in the lecture?

Sucrose, fruits, honey, and corn syrup.