Adv chemistry exam 1

identify structures in the liver

(saturated with hydrogens)

unsaturated: doesn’t have all the hydrogens it could possibly have; has a at least 1 double bond

has double bond between 3rd and 4th carbon from far end away from the COO-/COOH

-Macrophages (monocytes that have migrated from blood vessels to tissue) that line the sinusoid (blood vessel in liver) -Act as scavenger, removing big particulates (complexes of coagulation factors and inhibitors, antibodies and antigens) from circulation, detoxifier, and antimicrobial

Prealbumin -AKA transthyretin (thyroxine-binding prealbumin) -Transports vitamin A and thyroid hormones -Sensitive index of protein nutrition Prothrombin (factor II) PLT count

Markers of liver function (synthesis) -Total protein -Albumin -Transports insoluble compounds -FAs -Bilirubin -Calcium -Lipophilic medications -Keeps water in vasculature -Decrease albumin = edema -Moderately informative of protein nutrition -3-week half life

factor VII (clotting factor) -half-life of 4 hours -Basis of INR, depends on adequate activity and levels of factor 7. No protein = low factor 7 activity prealbumin -Half life of 2-3 days

Total and conjugated bilirubin ALP activity gamma-GT -Participates in glutathione detoxification

AST ALT

-Liver doesn’t metabolize glucose (saves it for brain since fatty acids and lipoproteins can’t cross blood-brain barrier) -Liver utilizes fatty acids

Conversion of glucose to glycogen (storage form) Instigated by insulin

Break down of glycogen (storage form) to glucose Instigated by glucagon

Breakdown of cholesterol and triglycerides to form free fatty acids Instigated by glucagon and epinephrine Forms 3 fatty acids and 1 glycerol Transported via blood stream with cholesterol as lipoprotein Other cells take up FAs, liver uses glycerol

Synthesis of fatty acids from acetyl CoA

Formation of glucose-6-phosphate from noncarbohydrate sources Instigated by glucagon

Metabolism of a glucose molecule to pyruvate or lactate for production of energy

RBCs use glucose to run salt pumps -Keeps glutathione in reduced state? (intact glucose-6-phosphate pathway) Important antioxidant Can be depleted in G6PD deficiency, acetaminophen overdose Detoxifies both xenobiotic and endogenous compounds Facilitates excretion of toxins from cells, body Directly neutralizes compounds Scavenges oxidants (superoxide anion, hydroxyl radical, nitric oxide, carbon radicals) Recycles vitamin C and E

AST/ALT = liver cell injury -Leak out of damaged cells ALP, gamma-GT: hepatobiliary function -Induced by biliary stasis or obstruction/hepatobiliary disease

ALT More liver specific

Build-up of ammonia

Transport (derivative of glucose) glucuronic acid Catalyze covalent addition of sugars to lipophilic molecules Eliminates exogenous chemicals and by-products of endogenous metabolism Controls levels and distribution of endogenous signaling molecules Liver attaches polar and charged glucose (glucuronates) to facilitate excretion through bile

Defect in bilirubin uridine diphosphate glucuronosyltransferase (bilirubin UGT) Mild Unconjugated hyperbilirubinemia is induced by stress/illness

Rare Autosomal recessive disorder Loss of UGT1A1 Severe unconjugated hyperbilirubinemia and kernicterus

Haptoglobin -scavenges free heme from blood Removes coagulation-inhibitor complexes, hemopexin-heme, haptoglobin-globin complexes

Renal failure Trauma CHF Aortic valve disease Pulmonary embolism Renal insufficiency Pneumonia Septic shock

Transports dietary triglycerides

Remnant of chylomicron after delivery of triglyceride to adipose tissue Taken up by liver

Transports endogenous triglyceride to adipose

Intermediate density lipoprotein Remnant of VLDL after delivery of triglycerides Taken up by liver

Transports cholesterol Size is clinically significant Receptor-mediated uptake in liver and adipose (LDL-R)

Important in reverse cholesterol transport

“Digests” triglycerides transported to adipose enzyme

Enzyme Transports cholesterol out of blood and tissues via cholesterol esterification Uses phosphatidylcholine

Enzyme Uses acyl-CoA Catalyzes formation of cholesteryl esters from cholesterol

Atherogenic Structural protein for VLDL and LDL Ligand for binding to LDL receptor Mainly on VLDL, IDL, LDL

Mainly on HDL, chylomicrons Activator of LPL and LCAT

Mainly on chylomicrons, VLDL Essential cofactor for LPL

Structural protein for Lp(a) Inhibitor fo plasminogen activation Increases risk for heart disease and stroke Similar to LDL -Has aspoB and aspo(a) attached to surface -Contains oxidized phospholipids

Increased risk of heart disease and stroke Genetic predisposition

Associated with raised triglycerides and decreased HDL-c levels Adiposity and diabetes Genetic predisposition

atherosclerosis

Coronary artery disease

Changes in LDLR gene Results in increased LDL Caused by mutations in APOB, LDLRAP1, or PCSK9 gene LDLR is unable to remove cholesterol from blood

Very low LDL and VLDL Cause by genetic variants in MTTP gene; autosomal recessive -Makes microsomal triglyceride transfer protein -Produces beta-lipoproteins (carry dietary fats and cholesterol)

LDLC = (Total Cholesterol) − (HDLC) − (TGs/5) TGs/5 = VLDL

Triglycerides >400, <100 Non-fasting patient Patient with type I or III hyperlipoproteinemia

Type I: impaired chylomicrons

Type IIa: Receptor defects in CSK9 protein

Type IIb: Impaired clearance of VLDL

Precipitation -Add precipitant -All non-HDLs precipitate -Centrifuge sample -Measure HDL in supernatant colorimetry

LDL Cholesterol

Dismantles LDLR

Inhibits PCSK9 LDLR not broken down; cholesterol/LDL taken into cells and plasma levels lowered Monoclonal antibody against PCSK9

Competitive inhibitors of HMGCoA reductase Starves cells of cholesterol; increases expression of LDLR

Keeps iron in reduced state Increases iron absorption

Deficiency -Low iron -scurvy Excess -Iron overload

Increases iron absorption

Increases absorption

Decreases absorption

Decreases absorption

Decreases absorption

Decreases absorption

Decreases absorption

Increased absorption

Transports iron Chelates iron to be rendered soluble Prevent formation of reactive oxygen species

Increases with hereditary hemochromatosis Stores iron inside cells

Transfers iron from circulation (transferrin) into cells

Senses iron status On hepatocytes

Duodenal ferric reductase Reduces iron from 3+ to 2+ for absorption

Divalent metal transporter-1 Absorbs Fe2+

Liver hormone Regulates iron absorption and mobilization Increased hepcidin = decreased iron

Transmembrane copper-dependent ferroxidase Effective iron transport from intestinal cells to circulation Dependent on hepcidin levels

With hephaestin: oxidizes and binds ferric iron to transferrin

Transports iron across the membrane from cell to circulation Bound by hepcidin (which decreases iron absorption)

Controls levels of hepcidin

Controls levels of hepcidin Mutation causes hereditary hemochromatosis

Keeps tight hold on iron to prevent parasites/bacteria from getting ahold of it

Serum iron/TIBC x 100 Example: Serum iron = 100 micrograms/L TIBC = 300 micrograms/L 100/300 * 100 = 33% transferrin saturation

70-100% saturation = iron overload (hemochromatosis) 10% saturation = iron deficiency 35% = normal

Both should agree, differences in methodology TIBC -Radiated iron is added to a sample -The more radiated iron is attached to transferrin, the more open spaces there are on transferrin -Excess iron is removed -Iron is dissociated from transferrin -Measurement of iron is indication of transferrin levels -More iron after dissociation = more transferrin Immunochemical -Anti-transferrin antibody attaches to transferrin

TIBC Ferritin Transferrin Hemoglobin

TIBC is low Stores are high

TIBC is high Stores are low

TIBC low or normal Iron high Ferritin high

TIBC high Ferritin high Serum iron high

In plasma Catalyze oxidation and binding of ferric iron to transferrin

Basolateral membrane of RBCs Catalyze oxidation and binding of ferric iron to transferrin

Quantity goes down in inflammation Example: ferritin, transferrin

Ferritin -Storage form of iron -Use all storage when absorption of iron is low -Low ferritin = early sign of iron deficiency

Ferritin increased

Regulates ferroportin High hepcidin turns off ferroportin Keeps iron inside of cells Potentiates excretion of iron; soughs enterocytes into feces

Is positive acute phase reactant -Increases in inflammation -Keeps iron inside of cells to keep it away from parasites/bacteria Increases in ACD Decreases in hemochromatosis