Iron Metabolism and Blood Disorders

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Questions and Answers

What role does Ferroportin play in the body?

Stores iron in Fe3+ form

Transports Fe2+ into erythrocytes (correct)

Deactivates the 50S ribosomal subunit

Activates gluconeogenesis

Which of the following statements about Glucokinase is true?

Only active in muscle cells

Has a low Km, leading to rapid glucose uptake

Functions primarily in the liver (correct)

Inhibits insulin secretion

In a patient with G6PD deficiency, which of the following is likely to occur?

High levels of reduced glutathione

Decreased susceptibility to oxidative stress

Increased reactive oxygen species in RBCs (correct)

Enhanced glycolysis in the liver

What is the primary cause of Sickle Cell Anemia?

Point mutation in the B globin gene Signup and view all the answers

What is the main action of Citrate in metabolic processes?

Inhibits PFK1 and glycolysis Signup and view all the answers

Which enzyme is responsible for the transport of iron in the bloodstream?

Transferrin Signup and view all the answers

What occurs in Hereditary Spherocytosis?

Genetic defect in the RBC cell membrane Signup and view all the answers

Which of the following best describes I Cell Disease?

Defect in N-acetylglucosamine-1-phosphotransferase Signup and view all the answers

What is a primary consequence of untreated phenylketonuria (PKU)?

Decreased levels of dopamine Signup and view all the answers

What enzyme is responsible for the first step of glycogenolysis?

Glycogen phosphorylase Signup and view all the answers

Which process occurs in the G1 phase of the cell cycle?

Nucleotide excision repair Signup and view all the answers

What is the main defect in Ataxia telangiectasia?

Inability to perform non-homologous end joining (NHEJ) Signup and view all the answers

What condition can result from excessive levels of trypsin?

Pancreatitis Signup and view all the answers

What natural consequence can occur due to chronic blood loss in liver cirrhosis?

Anemia Signup and view all the answers

How is methemoglobinemia characterized in terms of hemoglobin?

Conversion of Fe2+ to Fe3+ Signup and view all the answers

What is the final step in base excision repair?

Closing the DNA strand with ligase Signup and view all the answers

Study Notes

Iron Metabolism

Ferroportin: transports Fe2+ into erythrocytes
Transferrin: transports Fe in blood to bone marrow and macrophages
Ferritin: stores iron as Fe3+

Hemoglobinopathies and RBC Disorders

Hereditary Spherocytosis: a genetic defect in the RBC cell membrane
Sickle Cell Anemia: a point mutation in the β globin gene: Glutamic acid → Valine

Drug Effects

Erythromycin: deactivates the 50S ribosomal subunit
Metformin: inhibits complex I of the electron transport chain, reducing ATP production and activating cAMP pathways, which ultimately stops gluconeogenesis
Phenytoin: can cause normocytic anemia
Sulfonylureas: may cause hypoglycemia

Glucose Metabolism

Glucokinase: has a high Km, leading to glucose uptake after a meal but with a lag due to hexokinase saturation
Muscles and adipocytes: have GLUT4 transporters
Liver: has GLUT2 transporters
Glycogen stores: last 12-18 hours

Gluconeogenesis

Substrates for gluconeogenesis: glycerol, lactate, pyruvate, amino acids, propionyl CoA
Citrate: inhibits PFK1 and glycolysis, activating fatty acid synthesis

Glycogen Metabolism

Glycogenolysis: glycogen phosphorylase is the first step, glycogen 6-phosphatase is the last step
Branching enzyme: α 1,4-glucosidase, α 1,6-glucosidase
Debranching enzymes: 4:6 transferase

DNA Repair

Nucleotide excision repair (NER): happens in G1
Base excision repair (BER):
- Step 1: DNA glycosylase removes the base
- Step 2: endonuclease at 5' and lyase at 3' end to cut
- Step 4: DNA polymerase fills in
- Step 5: DNA ligase closes

Genetic Disorders

G6PD deficiency: lack of G6P dehydrogenase → no reduced glutathione → RBCs are more susceptible to oxidative stress. Intolerance of fava beans and sulfa drugs. May present with back pain and bloody urine.
Pyruvate Kinase deficiency: decreases glycolysis, decreases ATP, affects the RBC membrane, and increases the NADH:NAD+ ratio.
I-Cell disease: mutation in N-acetylglucosamine-1-phosphotransferase, similar to Hurler's syndrome. Skeletal abnormalities and intellectual disability. Inability of cells to create mannose-6-phosphate, so enzymes are secreted extracellularly instead of to lysosomes.
Mannose-6-phosphate: directs enzymes to the lysosome
Mucopolysaccharidoses (MPS) (Hurler's): lysosomal proteins are moved out of the cell.
Maple Syrup Urine Disease (MSUD): no α-ketoglutarate dehydrogenase complex; branched-chain amino acids are affected and accumulate. Most common AA to accumulate is leucine. Typically manifests within a few days of birth, and urine is sweet-smelling.
Phenylketonuria (PKU): no conversion of phenylalanine (F) to tyrosine because phenylalanine hydroxylase is lacking.
Atypical PKU: no dihydropteridine reductase causes no F to tyrosine and lowers dopamine.
Homocystinuria: no cystathionine β synthase or methionine synthetase leads to accumulation of homocysteine.
Alkaptonuria: no homogentisic acid oxidase results in a buildup of homogentisic acid. Therapy includes limiting the intake of tyrosine or phenylalanine. This condition results in a buildup of brownish or black pigment in the skin, sclera, bone marrow, connective tissue, and dark urine.
Xeroderma pigmentosum: due to nucleotide excision repair defect
Lynch syndrome: due to defect in DNA mismatch repair

Other

RNA polymerase 1: transcribes rRNA
RNA polymerase 2: transcribes mRNA
RNA polymerase 3: transcribes tRNA
Taut form of Hb: found in peripheral tissues where O2 content is low.
Chronic blood loss: common in liver cirrhosis secondary to alcoholism. Blood loss results in anemia.
Ataxia telangiectasia: due to inability to do non-homologous end joining (NHEJ) in double-stranded DNA breaks. Presents with ataxia, spider adenomas, and IgA, G, E deficiency.
Aplastic anemia: due to a defect in double-stranded DNA repair function.
Alpha-amanitin: affects DNA polymerase 2
Trypsin: a pancreatic enzyme. Over-release leads to pancreatitis.
Pepsinogen: a gastric enzyme.
Methemoglobinemia: causes a change from Fe2+ to Fe3+. May manifest with chocolate-colored blood and cyanosis.
In gluconeogenesis, pyruvate and oxaloacetate: are found in the mitochondria.
PFK-1: activated by insulin, AMP, ADP, F26BP. Inhibited by ATP, citrate, glucagon.
Inulin: tyrosine kinase
Glucagon: GPCR → adenylyl cyclase
Cortisol: increases blood sugar levels by increasing the metabolism of sugars, carbs, and proteins.
DKA: leads to hyperkalemia.
Stopping insulin supply: stops lactic acidosis in DKA.
Sensitivity: reduces false negatives.
Specificity: reduces false positives.
Phosphatidylcholine: makes up surfactant.
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Description

This quiz covers essential concepts of iron metabolism, hemoglobinopathies, and drug effects on red blood cells. You will also explore glucose metabolism, including the roles of various transporters and enzymes. Test your understanding of these critical topics in hematology and metabolic processes.