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Flashcards in Biochemistry Deck (161)
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Carbon monoxide poisoning

CO is generated as a byproduct of incomplete hydrocarbon combustion (eg, emission from automobiles in poorly ventilated spaces or a faulty home heater). CO has 220 times more affinity for Hgb than oxygen. Inhaled CO rapidly diffuses across alveolar membrane and binds tightly with heme-bound iron in Hgb, forming carboxyhemoglobin. Decreases oxygen content of blood by occupying oxygen binding sites. CO also inhibits release of oxygen from Hgb in tissues by altering conformation of Hgb to relaxed form with high affinity for oxygen. RESULT: leftward shift of oxygen dissociation curve and tissue hypoxia 2/2 deficient oxygen unloading. Tx is with 100% or hyperbaric oxygen.



Oxidation of ferrous iron (Fe++) to ferric iron (Fe+++) leading to formation of methemoglobin, which is unable to bind oxygen.


Maturity-onset diabetes of the young (MODY)

Mild, nonprogressive hyperglycemia that often worsens with pregnancy-induced insulin resistance 2/2 heterozygous mutation of glucokinase causing less beta cell release of insulin.



1. Glucokinase functions as glucose sensor in pancreatic beta cells (and hepatocytes) by controlling rate of glucose entry into glycolytic pathway.
2. Has a lower glucose affinity (increased Km) than hexokinase, but increased efficacy (higher Vmax).
3. GK varies the rate of glucose entry into the glycolytic pathway based on blood glucose levels. Induced by insulin.
4. Heterozygous mutations of the glucokinase gene cause a decrease in beta cell metabolism of glucose, less ATP formation, and decreased insulin secretion, producing MODY.
5. Homozygous mutations lead to fetal growth retardation and severe hyperglycemia at birth.


Pyruvate carboxylase deficiency

Catalyzes conversion of pyruvate to oxaloacetate for gluconeogenesis, requires biotin (B7) as a cofactor. Takes place in the mitochondria. Deficiency causes lactic acidosis (build up of pyruvate shunted to lactate) and fasting hypoglycemia (no oxaloacetate to use as substrate for gluconeogenesis).


Glucose-induced insulin release

1. Glucose enters beta cell through GLUT-2
2. Glucose is metabolized by glucokinase to glucose-6-phosphate.
3. G-6-P is further metabolized by glycolysis and TCA to produce ATP.
4. High ATP to ADP ratio within beta cell results in closure of ATP-sensitive potassium (Katp) channels.
5. Depolarization of beta cells results in opening of v-gated calcium channels.
6. High intracellular calcium causes insulin release.

Side note: GLP-1 receptor increases insulin exocytosis from beta cell by increasing intracellular cAMP.


Lactate dehydrogenase deficiency

LDH catalyzes conversion of pyruvate to lactate during anaerobic glycolysis. Deficiency causes decreased exercise tolerance and muscle stiffness.


G-protein coupled receptor pathway

1. G protein is a heterotrimer consisting of α, β, and γ subunits associated with intracellular domain of transmembrane receptor. α-subunit is bound to GDP.
2. Hormone binds and activates receptor causing α-subunit to undergo conformational change, releasing GDP and binding GTP.
3. GTP binding allows α-subunit to dissociate and act on other enzymes.
4. Gs α-subunit activates adenylate cyclase (AC), enzyme which converts ATP to cAMP.
5. cAMP activates protein kinase A, which is responsible for intracellular effects of G protein-mediated adenylate cyclase second messenger system.
6. PKA phosphorylates specific serine/threonine residues in various enzymes, leading to their activation or deactivation.
7. PKA also phosphorylates proteins that bind to regulatory regions of genes on DNA.
8. cAMP action is regulated by cAMP phosphodiesterase, which cleaves cAMP to its inactive form, 5'-AMP.
9. Drugs that inhibit cAMP phosphodiesterase lead to prolongation of actions of cAMP. eg, theophylline in bronchial asthma.


Hormone receptors that use Gs alpha-mediated cAMP second messenger system to mediate effects?

1. FLAT ChAMP + cGg
2. FSH
3. LH
5. TSH
6. CRH
7. hCG
8. ADH (V2-receptor)
9. MSH
10. PTH
11. calcitonin
12. GHRH = growth hormone releasing hormone
13. glucagon
14. Also: β1, β2, β3 (adrenergic Rs), D1 (dopamine R), H2 (histamine R), V2 (vasopressin/ADH R)


Hormone receptors that use cGMP second messenger system to mediate effects?

1. BAD GraMP (vasodilators)
2. BNP = b-type natriuretic peptide
3. ANP = atrial natriuretic peptide
4. EDRF (NO) = endothelium-derived relaxing factor aka NO


Janus tyrosine kinase (JAK)

JAK is a cytoplasmic protein activated by ligand binding to transmembrane receptors that lack intrinsic tyrosine kinase activity. JAKs phosphorylate receptor and activate cytoplasmic transcription factors called STATs (signal transducers and activators of transcription), which enter nucleus to promote gene transcription.


Hormone receptors that use JAK-STAT pathway (aka nonreceptor tyrosine kinase) to mediate effects?

1. PIGG(L)ET (think acidophils and cytokines)
2. Prolactin
3. Immunomodulators (aka cytokines IL-2, IL-6, IFN)
4. GH = growth hormone
5. G-CSF = granulocyte-colony stimulating factor
6. Erythropoietin (EPO)
7. Thrombopoietin (TPO)
8. When hormone binds, transmembrane receptors recruit Janus kinase from the cytoplasm, a tyrosine kinase that causes phosphorylation and activation of STAT nuclear transcription factors.


Receptor tyrosine kinase

1. Receptor with intrinsic kinase domain.
2. Receptor undergoes auto-phosphorylation when ligand binds.
3. SH2 (SHC?) adapter protein binds to phosphorylated tyrosine kinase, which then activates RAS.
4. RAS uses GTP to activate RAF, which then activates the MAP kinase pathway (MEK, MAPK), leading to amplification of signal and DNA transcription.


Hormone receptors that use receptor tyrosine kinases to mediate effects?

1. Insulin
2. IGF-1 = insulin-like growth factor 1
3. FGF = fibroblast growth factor
4. PDGF = platelet-derived growth factor
5. EGF = epidermal growth factor
6. MAP kinase pathway


Hormone receptors that use IP3 second messenger system to mediate effects?

2. GnRH
3. Oxytocin
4. ADH (V1-receptor)
5. TRH
6. Histamine (H1-receptor)
7. Angiotensin II
8. Gastrin
9. Also: HAVe 1 M and M.
10. H1
11. α1 adrenergic receptor
12. V1
13. M1 muscarinic receptor
14. M3 muscarinic receptor


Intracellular hormone receptors?

1. Progesterone
2. Estrogen
3. Testosterone
4. Cortisol
5. Aldosterone
6. T3
7. T4
8. Vitamin D
9. Think PET CAT on TV


Signaling pathway of steroid hormones

1. Steroid hormones are lipophilic and must circulate bound to specific binding globulins, which increase their solubility.
2. In men, increased sex hormone-binding globulin (SHBG) lower free testosterone leading to gynecomastia.
3. In women, decreased SHBG raises free testosterone leading to hirsutism.
4. OCPs and pregnancy cause increased SHBG, and thus OCPs can treat hirsutism and acne caused by androgens in PCOS.
5. Once hormones enter the cell, they can bind to the intracellular hormone receptor located in the nucleus or cytoplasm.
6. Binding of the hormone causes transformation of the receptor to expose DNA-binding domain and translocation to the nucleus, where it binds to enhancer elements in DNA.


Cyclic GMP signaling pathway (eg, in the corpus cavernosum)

1. Nitric oxide (NO) aka EDRF in corpus cavernosum binds to guanylate cyclase receptors.
2. Activated guanylate cyclase creates increased levels of cGMP.
3. cGMP activates protein kinase G, which mediates smooth muscle relaxation in blood vessels.
4. Smooth muscle relaxation (vasodilation) of the intimal cushions of helicon arteries leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection.
5. Sildenafil protects cGMP from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum of the penis, leading to longer erections.


Pigment stones

Most common in rural Asian populations, with increased incidence in women and elderly. Pigment stones account for only 10-25% of gallstones in US. Brown pigment stones typically arise 2/2 infection of biliary tract by E coli, Ascaris lumbricoides, or liver fluke Opisthorchis sinensis, which results in release of beta-glucuronidase by injured hepatocytes and bacteria. Beta-glucuronidase hydrolyzes conjugated bilirubin into unconjugated bilirubin in bile. Increased amount of unconjugated bilirubin in bile makes pigment gallstones more likely to precipitate out.



Converts cholesterol to bile acids. Sufficient activity of 7-alpha-hydroxylase reduces likelihood of cholesterol gallstone formation.


Heterozygous familial hypercholesterolemia

An AD LDL receptor defect that causes high LDL levels and increases risk of premature atherosclerosis. Homozygous familial hypercholesterolemia (rarer and more severe form) often presents with coronary heart disease/MI in childhood/adolescence.



1. Vitamin C deficiency impairs hydroxylation of proline/lysine residues on pro-alpha-collagen in the rough endoplasmic reticulum.
2. Defective hydroxylation of these residues severely diminishes the amount of collagen secreted by fibroblasts and impairs triple helix stability and covalent crosslink formation that helps collagen attain maximum tensile strength.
3. Scurvy occurs primarily among malnourished populations in the US, such as alcoholics, poor, elderly (tea and toast diet).
4. Sx of scurvy reflect impaired collagen formation: gingival swelling/bleeding, petechiae, ecchymoses, poor wound healing, perifollicular hemorrhages, coiled corckscrew hair.


Collagen synthesis

1. Collagen genes transcribed in the nucleus and translated by RER-bound ribosomes. Signal sequence directs growing polypeptide chain into RER.
2. Pre-pro-alpha-chains become pro-alpha-chains once the signal sequence is cleaved.
3. Hydroxylation (post-translational modification) of selected proline and lysine residues (vitamin C dependent) by prolyl hydroxylase and lysyl hydroxylase, respectively.
4. Glycosylation of selected hydroxylysine residues with galactose and glucose.
5. Assembly of pro-alpha-chains into procollagen triple helix.
6. Procollagen transferred from RER to Golgi apparatus and secreted into extracellular matrix.
7. Terminal propeptides cleaved by N- and C- procollagen peptidases to form insoluble tropocollagen.
8. Tropocollagen molecules spontaneously self-assemble into collagen fibrils.
9. Covalent cross links are formed by lysyl oxidase.


What causes bruises to look green several days after an injury?

Heme oxygenase converts heme from broken down RBCs into biliverdin, a green pigment.


How is heme metabolized?

1. Heme degraded to biliverdin (and CO and ferric iron) by Heme Oxygenase (contained in macrophages). Oxygen and electrons are provided by NADH and NADPH-cytochrome P450 reductase.
2. Biliverdin (green) is further converted to unconjugated bilirubin (yellow pigment) by Biliverdin reductase.
3. Unconjugated bilirubin is bound to albumin and transported to the liver.
4. In the liver, bilirubin is conjugated with glucuronic acid by bilirubin glucuronyl transferase (UGT) to form conjugated bilirubin, which is excreted by the liver as bile.
5. Conj. bilirubin is broken down in the colon by bacterial dehydrogenase to urobilinogen, which is then broken down to stercobilin, which gives stool its brown color.


Hemoglobin vs. myoglobin

Individual subunits of hemoglobin molecule are structurally analogous to myoglobin. If separated, monomeric subunits will demonstrate hyperbolic oxygen-dissociated curve similar to myoglobin, as myoglobin only has a single heme group and therefore does not experience heme-heme interactions. Myoglobin is a monomeric protein, the primary oxygen-storing protein in skeletal and cardiac muscle tissue, found only in the bloodstream after muscle injury.


Peptide bond formation

Catalyzed by peptidyl transferase on eukaryotic ribosomes


Lactic acidosis

An anion-gap metabolic acidosis that results from overproduction and/or impaired clearance of lactic acid. Ex. In septic shock, impaired tissue oxygenation decreases oxidative phosphorylation, leading to shunting of pyruvate to lactate after glycolysis, causing an increase in lactic acid formation. Hepatic hypoperfusion also contributes to the buildup of lactic acid, as the liver is the primary site of lactate clearance.


Causes of lactic acidosis

1. Enhanced metabolic rate (eg, seizures, exercise)
2. Reduced oxygen delivery (eg, cardiac or pulmonary failure, shock, and tissue infarction)
3. Diminished lactate catabolism due to hepatic failure or hypoperfusion
4. Decreased oxygen utilization (eg, cyanide poisoning)
5. Enzymatic defects in glycogenolysis or gluconeogenesis


Chronic myelogenous leukemia (CML)

1. Philadelphia chromosome mutation
2. t(9:22) BCR-ABL fusion protein
3. Sx. constitutional symptoms (eg, fatigue, weight loss, excessive sweating), splenomegaly, leukocytosis with marked left shift (eg, myelocytes, metamyelocytes, band forms)