Advanced Biology: Iron Metabolism & Anemias

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Questions and Answers

What is the primary function of transferrin in the body?

Transport iron in blood to bone marrow and macrophages (correct)

Store iron in the form Fe3+

Activate hexokinase for glucose uptake

Transport Fe2+ into erythrocytes

Which enzyme deficiency is associated with increased susceptibility to oxidative stress in RBCs?

Alpha-ketoglutarate dehydrogenase

G6P dehydrogenase (correct)

N-acetylglucosamine-1-phosphotransferase

Hexokinase

What causes the sweet-smelling urine in Maple Syrup Urine Disease (MSUD)?

Accumulation of valine

Deficiency in gluconeogenesis

Increased levels of homogenistic acid

Buildup of α-ketoacids, predominantly leucine (correct)

Which of the following best describes the defect in I Cell disease?

Underproduction of mannose-6-phosphate Signup and view all the answers

Which of the following is the role of glucagon in glucose metabolism?

Acts through GPCR and adenylyl cyclase Signup and view all the answers

What is the consequence of ferroportin deficiency?

Inability to transport iron into erythrocytes Signup and view all the answers

What effect does citrate have on the glycolytic pathway?

Inhibits PFK-1 and activates fatty acid synthesis Signup and view all the answers

Which condition is characterized by a point mutation in the beta globin gene?

Sickle cell anemia Signup and view all the answers

What is the main consequence of a deficiency in cystathionine B synthase or methionine synthetase?

Accumulation of homocysteine Signup and view all the answers

Which enzyme is deficient in atypical phenylketonuria (PKU)?

Dihydropteridine reductase Signup and view all the answers

What physiological condition does Kusmal breathing indicate?

Decreased pH Signup and view all the answers

Which repair mechanism occurs during the G1 phase of the cell cycle?

Nucleotide excision repair Signup and view all the answers

What is the effect of increased cortisol on blood sugar levels?

Increases blood sugar levels Signup and view all the answers

What is the first step in glycogenolysis?

Glycogen phosphorylase Signup and view all the answers

Which enzyme is affected by alpha amanitin?

DNA polymerase II Signup and view all the answers

What is the role of trypsin in the body, particularly in relation to pancreatitis?

It digests proteins aggressively Signup and view all the answers

Study Notes

Iron Metabolism

Ferroportin transports Fe2+ into erythrocytes.
Transferrin (TIBC) transports iron in the blood to bone marrow and macrophages.
Ferritin stores iron as Fe3+.

Hemolytic Anemias

Hereditary Spherocytosis: a genetic defect in the RBC cell membrane.

Antibiotic Mechanisms

Erythromycin deactivates the 50S ribosomal subunit.

RNA Polymerases

RNA polymerase 1 synthesizes rRNA.
RNA polymerase 2 synthesizes mRNA.
RNA polymerase 3 synthesizes tRNA.

Glucose Metabolism

Metformin inhibits complex 1 of the electron transport chain, reducing ATP production and inhibiting gluconeogenesis by activating cAMP pathways.
Glycogen stores last 12-18 hours.
Oral glucose tolerance test is used to diagnose diabetes mellitus.
Substrates for gluconeogenesis: glycerol, lactate, pyruvate, amino acids, and propionyl CoA.
Glucokinase has a high Km, allowing for glucose uptake after a meal, but with a lag due to hexokinase saturation.
Muscles and adipocytes express GLUT4, while the liver expresses GLUT2.

Metabolic Acidosis

Cyanide poisoning can lead to acidosis due to inhibiting the electron transport chain.

Enzymes and Cellular Locations

Transaminase is located in the cytoplasm.

Drug-Induced Anemia

Phenytoin can cause normocytic anemia.

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)

G6PD deficiency: lack of G6PD leads to decreased reduced glutathione, making RBCs susceptible to oxidative stress.
Symptoms: intolerance of fava beans and sulfa drugs, back pain, and bloody urine.

Pyruvate Kinase (PK) Deficiency

PK deficiency: decreases glycolysis, leading to reduced ATP and affecting the RBC membrane.
Consequences: Increased NADH:NAD+ ratio.

Pharmacokinetic Calculations

Clearance (Cl):
- Cl = (.7*Vd)/t1/2
- Cl = Vd*Ke
Volume of Distribution (Vd):
- Vd = (LD*F)/Cp
Loading Dose (LD):
- LD = Cp*Vd/F
Maintenance Dose (MD):
- MD = Cpclt/F

Sickle Cell Anemia

Sickle cell anemia: caused by a point mutation in the beta globin gene, substituting Glutamic acid with Valine.

I-Cell Disease

I-Cell disease: mutation in the N-acetylglucosamine-1-phosphotransferase, affecting lysosomal enzyme targeting.
Symptoms: similar to Hurler's syndrome, with skeletal abnormalities and intellectual disability.
Mechanism: inability to create mannose-6-phosphate, leading to extracellular secretion of enzymes instead of delivery to lysosomes.

Lysosomal Targeting

Mannose-6-phosphate directs enzymes to the lysosome.

Maple Syrup Urine Disease (MSUD)

MSUD: deficiency in branched-chain alpha-ketoacid dehydrogenase (B1), blocking degradation of branched-chain amino acids (isoleucine, leucine, valine).
Consequences: Increased alpha-ketoacids in the blood, especially leucine.
Symptoms: sweet-smelling urine, typically manifesting within a few days of birth.

Insulin Sensitivity

Insulin activates PFK-1, leading to increased glycolysis.
Sulfonylureas can cause hypoglycemia by increasing insulin secretion.

Citrate Metabolism

Citrate inhibits PFK-1 and glycolysis, but activates fatty acid synthesis.

Alkaptonuria

Alkaptonuria: deficiency in homogentisic acid oxidase, resulting in homogenistic acid buildup.
Symptoms: brownish or black pigment in skin, sclera, bone marrow, connective tissue, and dark urine.
Therapy: limiting tyrosine or phenylalanine intake.

Homocystinuria

Homocystinuria: deficiency in cystathionine beta-synthase or methionine synthetase, resulting in homocysteine accumulation.

Diabetic Ketoacidosis (DKA)

DKA: leads to hyperkalemia.
To stop lactic acidosis in DKA: stop insulin supply.

Phenylketonuria (PKU)

PKU: deficiency in phenylalanine hydroxylase, preventing conversion of phenylalanine to tyrosine.
Atypical PKU: deficiency in dihydropteridine reductase, leading to both phenylalanine accumulation and decreased dopamine levels.

Respiratory Acidosis

Kussmaul breathing: decreased pH, often seen in metabolic acidosis.

Glycogen Metabolism

Glycogenolysis:
- First step: glycogen phosphorylase.
- Last step: glucose-6-phosphatase.
Branching enzyme: alpha 1,4-glucosidase and alpha 1,6-glucosidase.
Debranching enzymes: 4:6 transferase.

DNA Repair Mechanisms

Xeroderma pigmentosum: defect in nucleotide excision repair.
Lynch syndrome: defect in DNA mismatch repair.
Nucleotide excision repair: occurs in the G1 phase of the cell cycle.
Alpha amanitin: inhibits RNA polymerase 2.
Ataxia telangiectasia: defect in non-homologous end-joining (NHEJ) for double-stranded DNA breaks.
- Symptoms: ataxia, spider angiomas, and IgA, G, and E deficiency.
Aplastic anemia: defect in double-stranded DNA repair function.

Hemoglobin Structure and Function

Taut form of Hb: found in peripheral tissues where oxygen content is low.

Liver Cirrhosis and Anemia

Chronic blood loss: common in liver cirrhosis secondary to alcoholism.
Consequences: leads to anemia.

Base Excision Repair

Step 1: DNA glycosylase removes the damaged base.
Step 2: Endonuclease cuts at the 5' end and lyase cuts at the 3' end.
Step 4: DNA polymerase fills in the gap.
Step 5: DNA ligase seals the break.

Cellular Location of Enzymes

Enzymes involved in glycogen storage are located in the cytosol.

Thiazolidinediones (TZDs)

TZDs: cause water retention.

Surfactant

Phosphatidylcholine: the main component of surfactant.

Sensitivity and Specificity

Sensitivity: reduces false negatives.
Specificity: reduces false positives.

Pancreatic and Gastric Enzymes

Trypsin: a pancreatic enzyme. Excessive release can lead to pancreatitis.
Pepsinogen: a gastric enzyme.

Methemoglobinemia

Methemoglobinemia: conversion of Fe2+ to Fe3+ in hemoglobin.
Symptoms: chocolate-colored blood and cyanosis.

Gluconeogenesis

Pyruvate and oxaloacetate: intermediates found in the mitochondria during gluconeogenesis.

PFK-1 Regulation

Activated by: insulin, AMP, ADP, fructose-2,6-bisphosphate (F26BP).
Inhibited by: ATP, citrate, glucagon.

Hurler's Syndrome

Lysosomal proteins: are secreted out of the cell in Hurler's syndrome.

Glycogenolysis

Glycogen phosphorylase: the first step in glycogenolysis.

TCA Cycle

Pyruvate to acetyl-CoA to citrate: the pathway of pyruvate entry into the TCA cycle.

DKA and Electrolytes

DKA: leads to hyperkalemia.

Cortisol and Glucose Metabolism

Cortisol: increases blood sugar levels by enhancing the metabolism of sugars, carbohydrates, and proteins.

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Description

This quiz covers key concepts in iron metabolism, hemolytic anemias, antibiotic mechanisms, RNA polymerases, and glucose metabolism. Test your knowledge on the transport and storage of iron, genetic defects affecting red blood cells, and important metabolic processes. Perfect for students studying advanced biology and biochemistry.