Biochem Heme Mini2

• Protein tagged for Hepatocyte denaturing by removal of surface sialic acid by neuraminidase
• Kuffer cells recognize asialoglycoproteins and engulf to destroy

• Protease inhibitor (anti-coagulation, anti thrombin)
• low levels in ZZ-homo deficiency -- pulmonary emphysema resulting from overactive protease
• Low level also a sign of hepatic transport disorder due to liver damage (trypsin inhibitor overstorage)

• Protease inhibitor (anti-coagulation AND anti-clot breaker)
• -- inhibits both thrombin (clotting) and plasmin (fibrinolysis)
• Onocotic pressure keeper in nephrotic patients (replaces albulmin)
• Elevation indicaties renal failure or analbuminenia as proteins are peed out

• Apoprotein Transferrin - transport Ferric Iron (3+)
• Increase in transferrin (TIBC) - is a sign of iron deficiency

• Fibrinogen clotting factor
• C3 compliment protein
• some reason has to with obstructive jaundice

• Unconjugated Bilirubin transport (from spleen to liver)
• Oncotic pressure
• drug transport (warfrin and penicillin)
• Decrease means nephotic syndrom, or tissue inflammation or blood loss (could be genetic as well)

Thyroid hormones T3/T4 transport

Vita A transport

• Free hemoglobin transport
• Scavenges hemoglobin diners from blood
• Used for intravescular hemolysis indicator (DIC would cause decrease in Hpt)
• Destroyed along with heme it transports

• Heme that escapes spleen and liver degradation is scavenged by hemopexin
• decrease Hpx could also be hemolytic anemia

• Copper transport
• absence results in wilson's disease and copper deposits in eye (kaiser fletcher ring)
• Transferrin

• increase in prego means neuro tube defect
• decrease in prego means down's syndrom
• increase in adult means liver cancer (cause the fuck are you doing producing a fetal protein liver...)

acute infection

• Liver makes a lot of enzymes
• --Choline esterases
• -- Transaminases (AST/ALT)
• -- Phosphotases (ALP/AP)
• -- GGT
• -- LDH
• -- CK

• degrades choline (neurotransmittor)
• Decrease in choline esterase:
• --overdose of choline esterase inhibitor (Myathenia gravis therapy)
• --Organophosphate poisoning
• --Scoline apnea (succinylcholine esterase deficiency)
• --Liver failure (it no make)

• Increase in choline esterase:
• --nephrotic syndrom (i pee it out)
• -- liver tumor (it make too much)

• Anasthetic
• Genetic Scoline apnea has deficient coline esterase for succinlcholine
• Over activation of anasthetic effects

• Aspartate transaminase
• -- Increase ALONE - MI/skeleto cell damage or RBC lysis
• -- Increase WITH ALT - acute liver hepatitus
• Normal increase with neonatal hemolysis due to RBC turnover

• Alanin transaminase
• --increase ALONE - liver cirrhosis/disease
• --Increase WITH AST - acute liver hepatitus

• Alkaline Phosphotase- released by hypertrophied cartilage to lay down calcium
• --Increase in ADULT WITH GGT means bile duct damage
• --Increase in ADULT WITHOUT GGT means bone tumor or some shit
• --Increase in CHILDHOOD/Placenta/After meals normal due to increase in bone formation and bile duct normal function
• use gammaGT to follow up billiary duct damage

• Billiary protein
• Increase means cholestatic liver Disease
• useful over AST < ALT < ALP (from least useful to most besides gamma GT)
• Also a sign of alcohol or drug abuse

• Lactate dehydrogenase
• increase in LDH1 - myocardio infarction
• increase in LDH5 - acute hepatitus

• CK-BB for brain tumors
• CK-MB for Myocardio infarctions
• CK-MM for muscle dystrophies

• mainly in pancrease
• acute pancreatitus - you are going to get neutrophilia as well.... GOOO NEUTROPHILS

• COX-1 inhibitor
• Thromboxane inhibitor (prostacylin inhibitor too but thromboxane more preferential)
• Will increase bleeding time test

• clotting factor
• increase platelet aggregation and number

• present on endothelium(bound to factor 8 to inactivate it), platelet surface, plasma soluble protein
• binds to GP1b receptors on other platelets, promote platelet aggregation
• Deficiency is von Wilibrand disease
• --increase bleeding time test

• major clotting factor
• intrinsic and extrinsic final effector
• self promote by activating 8a(tenase complex) and 5a(Prothrombin complex) and 11a (christmas activator)
• fibrin formation by cutting fibrinogen into fibrin and 13a(fibrin crosslinker) activation

• Christmast factor - forms 10ase complex with 8a and Ca2+
• binds platelet with vita K carboxylation
• Hemophelia B missing
• can be activated by extrinsic 7a

• Bound to von Wilibrand when inactive
• forms 10ase complex to activate 10a
• hemophilia A when deficient

• intrisinc
• 8a+9a---platelet
• with ca2+ turns 10agolden

• 7a bound platelet and tissue factor 3
• this is tested in PT test (no intrinsic activation)

• AntiThrombin III activator
• kills 12a, 11a, 9a, 10a, 2a and probably 7a
• not degraded

Anti-vita K, it no add COO- to factors 7, 9, 10, 2

• Adds COO- to 7, 9, 10, 2
• needed for blood clot
• babies sometimes have a deficiency

• first one of the intrinsic (don't need cause 2a can activate 11a too)
• pre-kallikren + HMWK+ collagen activates

• transglutamase
• cross links fibrin dimers
• activated by thrombin

• Dimers from inactive Fibrinogen
• activated by Thrombin
• forms dimers when activated and linked by 13a

• 10a+5a+2+Calcium
• 10a from tenase complex
• 5a is activated by 2a (or mechanical stress as shown by research paper)

• Cuts fibrin (clot buster)
• activated by tissue plasminogen activator and urokinase
• deactivated by alpha2 antiplasmin and plasminogen activator type 1/2

• plasmin activator
• bust a clot

• anti-plasmin
• don't bust a clot
• alpha 2 macroglobulin also a anti plasmin

• Thrombinmodulin activated effector
• busts up 8a and 5a turning then back to 5/8
• effectivly bust up tenase and prothrombin complex respectivly

• needs thrombin to work
• -- an example of self regulation, lots of thrombin activate thrombinmodulin
• activates protein C,S
• deactivate 5a and 8a

• really checking for common pathway and extrinsic pathway
• Tissue factor 3 is added without collagenase, only extrinsic and common is activated
• Increased time in --vitamin K deficiency
• --factor 7 deficiency - over comsumption of substrates in DIC
• --warfrin therapy

• Add in kaolin to simulate collagen
• tests for intrinsic and common pathway, especially hemophilia A/B and von Wilibrand pathway (factor 8)

• adds nothing, tests for platelet number and functionality
• Increased time when taking asprin
• or when there is a decresae in von Wilibrand factor (reduced platelet to platelet adhesions)

• Transports ferrous iron into lumen cell
• controlled by hepcidin

• Iron storage in cell, ferric iron
• forms hemosiderin during iron overload
• plasma levels correspond to bone marrow levels
• decreased plasma levels means iron deficiency

• transports ferrous iron out of cell and into plasma
• hepcidin controlled (IL-6 indrectly controled)

• transports ferric iron within plasma from asportion to area of utilization
• High capacity and low saturation indicates anemia (due to iron deficiency)

• thalassemia
• genetic hemochromatosis DMT1 upregulation
• Lead poisoning

B12 with cobolt co-factor

• ilium absorption requring intrinsic factor (from parietal cells)
• lack of absorption is pernicious anemia

• Methymalonyl CoA Mutase -- B12 only
• Homoysteine methyltransferase -- WITH folate
• if abscent --> methylmalonic acidimeia (conclusive for B12 def)
• increased homosytein could mean B12 deficiency but also could be folate deficiency

• Methymalonic acidimeia (definitive)
• all folate anemia signs PLUS neurological disorders

• makes purines and thymidine
• mythylation of DNA/RNA
• needed for cell replication
• which is why cells can't divid (they grow but can't divid) without folate
• and why pregos need more folatic acid

• not really part of the lecture but B6 is ALAsynthase cofactor
• Ala synthase deficient means no Heme and produce sideroblast anemia
• no heme/hemoglobin == siderobplast, microcytic, iron overload anemia... pretty much

Leuvencore... i think, dude look at pharmaco

• Heme-->biliverdin-->bilirubin (this is in spleen)
• bilirubin +albumin = unconjugated indirect bilirubin (this is in plasma right out of spleen)
• bilirubin -albumin + glucuronic acid = conjudated direct bilirubin-diglucuronide (this is in hepatocyte)
• direct bilirubin --> bile --> gut --> poop or reuptake

• strong anti-oxident and produce steroids
• pentose phosphate pathway made by G6PDH
• shortage of NADPH means excess H₂O₂
• this will be the way RBCs lyse and aqumulate heinz bodies (heme fragments) in G6PDH def

• can't lead with reactive O₂ because NADPH not made from the pentose phosphate pathway
• jaundice resulting from hemolysis
• Heniz body (oxidative stress) Hb degraded hemolytic anemia

• Hemoglobin bound to ferric iron without oxygen
• none functional, results from oxidative compound poisoning
• Methemoglobin reductase to reverse

Congenital His-Try mutation that favors oxidation of ferrous iron to ferric once bound to hemoglobin

• alpha/gamma hemoglobin
• high affinity for O2 low affinity for BPG
• can't form salt group with BPG so decrease affinity for its negative allosteric regulator (BPG)
• His --> Ser
• Will take O2 from Hb (from mother) like Myoglobin

• CO high affinity for Hemoglobin 25k times
• Irreversible
• 0.1% CO is lethal

• High affinity for O2
• takes from Hemoglobin
• gives to cytochrome oxidase in ETC
• O2 storage in muscle

• Hemoglobin trait
• Each successive O2 addition increase affinity for next O2 and O2 is scavenged
• Each successive O2 subtraction decreases affinity and all O2 is completely released
• Low [O2] low affinity --> release all O2
• High [O2] high affinith --> bind all O2

• neg allosterics help decrease O2 affinity thus release at site of need
• all are metabolic by products
• BPG>CO2>Low pH
• stablize T(deoxy state)

• Hemoglobin trasports small fraction in carbamate
• mostly as HCO₃^- (CO₂+H₂O-->H₂CO₃-->HCO₃^-) in tissue rich in CO₂
• Hb will buffer extra H⁺
• Once at lung low CO₂ drive reaction in reverse and HCO₃^- is turned back into CO₂ and H₂O
• Cl^- used to balance ion concentration

• Perfect enzyme, completely converts
• CO₂+H₂O --> H₂CO₃ and reverse
• depending on concetration