Term
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Definition
substrate analogue of tetrahydrofolate and is used as chemotherapeutic agent to treat cancer or auto-immuno diseases
Tetrahydrofolate is the enzyme cofactor for the “Dihydrofolate Reductase”, which is important in the biosynthesis of purines and pyrimidines.
Methotrexate binds a thousand-fold better than tetrahydrofolate to the enzyme and blocks nucleotide base synthesis, which in turn, inhibits cell growth.
This class of drug is referred to anti-metabolite drugs. It slows down cell proliferation. |
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Term
| Plasma Enzymes in Clinical Diagnosis |
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Definition
| Intracellular enzymes from different tissues are released into blood plasma when the cells are ruptured. An increase of certain tissue-specific enzymes in plasma suggests the damage of the tissue. The level of enzyme activity in plasma correlates with the extent of tissue damage. |
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Term
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Definition
“Suicide Inhibitor” for Xanthine Oxidase. It is used to treat gout by
inhibiting urate production. (High urate concentration causes Gout) Inhibits active site |
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Term
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Definition
blocks the synthesis of bacterial cell wall by inhibiting the glycopeptide transpeptidase
Penicillin binds as a
Transition state analog
Penicillin also acts as a
suicide inhibitor that modifies
The active site of the enzyme |
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Term
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Definition
ANTIVIRAL
Once phosphorylated by dGMP kinases serves as nucleoside analogue for dGTP. Viral thymidine kinase has low specificty->termination of DNA chain. Human Thymidine Kinase has high specificity so doesn't interfere. |
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Term
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Definition
protease inhibitor for treatment of AIDS.
Crixivan is a transition state analogue of HIV protease. HIV protease cleaves multi-domain viral protein to become
active and infectious. Crixivan mimics the tetrahedral intermediate of the HIV protease. |
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Term
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Definition
block the production of Angiotensin II from Angiotensin I as cayalyzed by ACE and reduces blood pressure in hypertension.
Angiotensin-converting enzyme is a metalloprotease responsible for the production of Angiotensin II which increases renal fluid and electrolyte retention, contributing to hypertension. |
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Term
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Definition
| Example of competitive ACE inhibitor |
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Term
| Organophosphorus compounds |
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Definition
| inhibit acetylcholine esterase by forming an irreversible covalent adduct with the active site serine. The increase in acetylcholine leads to muscle paralysis. They are used in pesticides and nerve gas for their toxic effect. |
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Term
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Definition
| Antidote for poisoning with organophosphorous compounds. Parlidoxime can replace the alkylphosphate attached at the active site and reactivate the acetylcholine esterase. |
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Term
Statin drugs
ex:Lovastatin |
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Definition
Used in treatment of Familial hypercholesterolemia. Inhibit the key
enzyme, HMG-CoA reductase in the
cholesterol biosynthetic pathways.
Lovastatin has a structure similar to the HMG(3-hydroxyl-3-methylglutaryl)
moiety and acts as competitive inhibitor. |
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Term
| G-6-P dehydrogenase and hemolytic anemia |
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Definition
G-6-P produces NADPH (important for maintaining high level of reduced glutathione in cell and thus for membrane integrity)A mutation alters thermal stability of the enzyme but not the catalytic function. Reduction of active G6P dehydrogenase shortens the lifetime of the red cell and leads to hemolytic anemia.
Also some genetic variants show susceptibility to drug-induced hemolysis. Harmless drugs/fava beans |
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Term
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Definition
Genetic cause is deficiency a1 anti-trypsin and excess elastase in lung.
Smoking can cause oxidative inactivation of a1 antitrypsin (the oxidation of methionine to sulfoxide). The oxidized a1 antitrypsin has low affinity to elastase. |
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Term
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Definition
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Term
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Definition
| amount of hemoglobin per red cell |
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Term
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Definition
product of the volume of the red cell and the volume of the whole blood
Hematocrit = RBC x MCV |
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Term
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Definition
Average hemoglobin concentration per red cell
MCHC = MCH/Hematocrit |
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Term
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Definition
| gives number of red cells |
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Term
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Definition
| decrease of albumin level in blood, which is due to liver diseases, hemodilution, increased exudative process and leakage to extravascular space. The drop of oncotic pressure usually results in edema. |
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Term
| Serum albumin transport functions |
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Definition
| fatty acides, thyroxine, steroids, bilirubin, tryptophan, cystine, calcium |
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Term
| Deficiency of a1-Antitrypsin |
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Definition
| congenital or acquired. All result in emphysema, hepatic cirrhosis and respiratory distress syndrome. |
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Term
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Definition
the largest plasma protein (720,000 Da). Its major function is to inhibit a variety of proteases. It is capable of trapping the protease. The complex is rapidly cleared from circulation by binding to receptor expressed in macrophages and heptocytes.
also functions as a binding carrier and targeting protein for cytokines and growth factors. |
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Term
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Definition
It binds free hemoglobin which is released from red cell destruction. Free hemoglobin dissociates into a and b dimers that are bound to haptoglobin and the complexes are subsequently removed through the reticuloendothelial system, which degrades the heme groups to iron and bilirubin. Iron can be reabsorbed.
prevent free hemoglobin from appearing in glomerular filatrate in kidney and being secreted into urine. It takes up all the free hemoglobin from serum and targets them for digestion. |
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Term
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Definition
major transport protein for copper. helps export copper from the liver to peripheral tissues.
decrease of ceruloplasmin in plasma is a sign of Wilson’s disease.
also plays a role in iron utilization. It possesses a mild ferroxidase activity which oxidizes ferrous ion (Fe2+) to ferric ion (Fe3+) which binds to transferrin for transport in blood.
Ferritin binds Fe2+
for storage in cell
Transferrin only binds Fe3+
for transportation in serum |
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Term
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Definition
genetic defect in Cu-transport ATPases. (P-type ATPase) The defect prevents incorporation of copper into ceruloplasmin and leads to impairment of biliary copper excretion and increased urinary copper. The progressive accumulation of copper in liver results in chronic liver disease. The defect also affects brain function resulting in neuropsychiatric problems. Copper deposition into the cornea of the eye produces the classic appearance known as Kayser-Fleischer rings, green to brown deposits of copper in Descemet’s membrane in the limbus of the cornea.
an autosomal recessive disorder associated with toxic accumulation of copper in liver and brain. |
|
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Term
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Definition
| Another copper related disease associated with copper uptake by another Cu-ATPase. |
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Term
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Definition
major iron storage protein in all cells of the body
concentration of ferritin in plasma is proportional to the amount of stored iron and is one of the best indicators of iron deficiency. |
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Term
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Definition
| derivative of ferritin and is found in liver, spleen and bone marrow. It forms aggregates that slowly release iron when iron deficiency exists. |
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Term
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Definition
In plasma reduces free iron concentration in blood which is toxic to the body. The transferrin-iron complex enters cells by receptor-mediated endocytosis.
responsible for the transport of iron from its site of absorption in the intestine or in blood to red cells precursors in bone marrow. Also reduces iron losses through urine. |
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Term
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Definition
| Lipoproteins constitute a family of complexes composed of lipids and proteins whose sole function is to transport hydrophobic triglycerides, phospholipids and cholesterol in blood. |
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Term
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Definition
elevated in a variety of acute inflammatory diseases.
CRP is synthesized in liver and released into plasma. In normal healthy individuals the CRP level in plasma is very low (0.8 mg/dL) below the detection limit of most routinely used methods. In response to acute inflammation, CRP level increases drastically to 1,000 fold with a short half-life of 19 hrs.
CRP plays an important role in the recognition of microbial organisms and functions as immunomodulator in host defense. CRP initiates opsonization, phagocytosis and activation of complement, neutrophils and monocyte-macrophages. CRP also recognizes necrotic tissues or inflammation related to autoimmuno-response. |
|
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Term
| acute-phase reactants (APRs) |
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Definition
a group of proteins whose plasma concentration changes in response to inflammatory states from infection, surgery, trauma, myocardial infarction, malignancy, and condition associated with tissue necrosis.
Some increase (+) while others decrease (-) |
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Term
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Definition
| most common. IgG is actively transported across the placenta. circulates in high concentrations in blood protecting all tissue spaces. eliminate small, soluble antigenic proteins through aggregation and enhanced phagocytosis by reticuloendothelial system. |
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Term
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Definition
large molecular weight pentamer.
predominant early antibody synthesized in response to an antigen. made by the fetus in utero (IgM begin to increase as IgG levels decrease) |
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Term
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Definition
| predominant immunoglobulin in secretions such as saliva, colostrum, human milk, tears as well as gastrointestinal and respiratory secretions. antiseptic barrier which protects mucosal surfaces. can promote phagocytosis, cause eosinophilic degranulation and activate complement. |
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Term
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Definition
The one associated with allergic reactions.
found on mucosal surfaces. IgE triggers histamine release when antigen binds to it and is a defense against parasites. |
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Term
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Definition
| found on cell surfaces and its precise function remains unclear. |
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Term
| Multiple Myeloma (plasma cell myeloma) |
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Definition
| the most common form of symptomatic monoclonal gammopathy. multiple tumorous masses of neoplastic plasma cells scattered through-out the skeletal system, which morphologically show up as multifocal destructive bone tumors. |
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Term
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Definition
Appearance of monoclonal antibodies in plasma signifies the proliferation of a single B cell clone which leads to a single, dense band in the gama region.
Monoclonal immunoglobulins are associated with diverse malignant pathologies |
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Term
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Definition
| igGk light chains in blood-> urine as Bence-Jones proteins |
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Term
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Definition
any substance that can be related to the presence or progress of a tumor.
ex:AFP (alpha-fetoprotein) measurements in the management of a patient with a testicular teratoma |
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Term
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Definition
Fucose-Gal-NAG
biosynthetic precursor of both A and B substances. It forms the common back bone. It is found in blood type O. |
|
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Term
| enzyme for gneration of H substance |
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Definition
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Term
| Type A blood enzyme for synthesis |
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Definition
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Term
| Type B blood enzyme for synthesis |
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Definition
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Term
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Definition
| His-143 is replaced by Ser, it thus loses its BPG binding activity. So binds O2 with greater affinity than maternal Hb. |
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Term
| 2,3-BPG levels allows adaptation at high altitude with low oxygen pressure. |
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Definition
| High altitude->high 2,3-BPG |
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Term
| Carbon monoxide poisoning |
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Definition
| tight complex with the heme group which is 250 times tighter than O2. CO completely displaces O2 from hemoglobin. |
|
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Term
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Definition
| originate from vitamin B12 and folate deficiencies. The lack of nutrients leads to diminished erythropoiesis-->abnormally large erythroid precursors and red cells due to defective cell maturation and division. anemic condition. |
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Term
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Definition
1) Methylcobalamin(a form of VitB12) as cofactor to methionine synthase which catalyzes homocysteine to methionine.
2)Propionyl CoA carboxylase and methylmalonyl CoA mutase require vit B12 and biotin as cofactors.Convert propionyl coA to succinyl coA (TCA cycle intermediate) |
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Term
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Definition
| Component hemoglobin chain found only in embryo and fetus |
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Term
| Sickle cell anemia (HbS) disease |
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Definition
homozygous recessive genetic disorder due to a single nucleotide point mutation in the b-globin gene (Glu-6 to Val-6).
The mutated hemoglobins (HbS – a2bs2) form rigid, insoluble, fibrous polymers in the deoxygenated state and make the erythrocytes rigid and elongated. Sickle cell erythrocytes occlude blood flow in capillaries resulting in hemolytic anemia.
sickle cell erythrocytes survive better in malaria infections and have high occurrence in populations where malaria is the major infectious disease.
Sickle cell disease causes lifelong episodes of pain (“crises”), chronic hemolytic anemia and increased susceptibility to infections in childhood.
Therapy involves proper hydration, antibiotic therapy, analgesics and blood transfusion with packed red cells. (The side effect of packed red cells transfusion is iron overload – hemosiderosis) |
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Term
| Inheritance pattern of sickle cell trait compared to other chain defects |
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Definition
b-globin chain defects have very predictable outcome since one b-globin
gene is inherited from each parent.
a-globin chain defects have a more complicated inheritance pattern because
two a-globin genes are inherited from each parent. |
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Term
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Definition
autosomal recessive
single mutation of b-chain (Glu-6 to Lys-6)
Benign disorder. It shows mild chronic hemolytic anemia and splenomegaly.
do not experience vasoocclusive crises, sequestration crises or infections prevalent among patients with Hb S sickle cells. |
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Term
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Definition
benign disorder with microcytic red cell (average MCV 72 fl) but no anemia
most common variant after Hb S |
|
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Term
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Definition
| syndromes result from an imbalance in globin chain production, It is almost always owing to underproduction of one or two types of globin chains. |
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Term
| thalassmemia minor vs. thalassmemia major |
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Definition
| severity of the clinical syndrome is directly associated of the percentage of the mutated globin protein in blood. Heterozygotes give rise to the thalassmemia minor and homozygotes give rise to thalassmemia major. |
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Term
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Definition
POINT Mutation-> diminished synthesis of structurally normal b-globin chains, coupled to unimpaired synthesis of a chains.
excess a chains form aggregates inside red cells which is destroyed in spleen. The hemolysis of red cells leads to anemia and tissue anoxia on one hand and the released hemoglobin causes decrease in haptoglobin and overloading of iron in heart and liver. Treatment may involve transfusion and chelating therapy to prevent iron overloads.
The deficiency of b–globin chains is masked at birth by the production of the g-globin chains (Hb F), but as the switch from g-globin to b–globin production proceeds, the severity of the clinical and hematologic expression increases.
To overcome the anemic condition, the bone marrow compensates and increases eyrthropoesis. Chornic b-thalassemia results in bone marrow expansions, which cause skeletal deformities. |
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Term
| a-Thalassemia (Thalassemia1/2) |
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Definition
DELETION of all or part of one or both a-globin genes results in a-thalassemia.
loss of one gene is classified as Thalassemia-2 and loss of both gene as Thalassemia–1. |
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Term
| Thalassemia 1 (HbH vs. Hb-Barts) |
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Definition
Hb H is caused by the formation of tetrameric (b4) and Hb-Barts is caused by the formation of (g4).
HbH:aggregation of B4 Hb->Heinz bodies
Hb Barts: binds O2 very tightly->hydrops fetalis (death in utero/pre-mature birth) |
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Term
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Definition
Red cells from non-human sources.
Need to block immuno-response from host for different blood groups etc. "(methoxypolyethylene glycol)
The blood substitute should maintain blood volume and pressure |
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Term
| Side effect of having free hemoglobin in blood |
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Definition
Generation of reactive oxygen radicals.
Free hemoglobin binds NO which causes constriction of blood vessels and hypertension.
Cause kidney failure.
Immuno-reaction. |
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Term
| Recombinant human serum albumin |
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Definition
| Major artificial blood carrier used. Can be used in high concentratio and is not attacked by immune system. |
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Term
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Definition
another artificial oxygen carrier used prior to albumin heme. No longer widely used.
In both recombinant and lipid, heme group must be protect to avoid oxidation. |
|
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Term
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Definition
| deficiency of lactase, the enzyme that cleaves the b-1-4 linkage in lactose. Metabolites of lactose produced by colonic bacteria increase the osmotic pressure and produce gas. |
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Term
| Gastric and duodenal ulcer |
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Definition
Gastric ulcer can be caused by overproduction of acid in the stomach by the parietal cells.
The treatments include neutralization of the effects of acid (antiacid) on lining of the stomach, drugs (H2 receptor antagonist – cimetidine) that block histamine H2 receptors or inhibitors of the gastric proton pump (omeprazole).
Omeprazole covalently modifies cysteine on a subunit of H+/K+ ATPase |
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Term
| Pancreatic failure/pancreatitis |
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Definition
| 90% is due to the blockage of the papilla of Vater by gallstone. The pancreatic enzymes are dammed up in the ducts and acini of the pancreas. Eventually, trypsinogen accumulates and overcomes the trypsin inhibitor in secretions. Once a small amount of active trypsin is present, the vicious circle of protease activation is induced that leads to the rapid digestion of large portions of the pancreas itself. |
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Term
| Sprue (non-tropical and tropical) |
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Definition
Malabsorption due to destruction of microvilli and decrease absorption area.
Nontropical Sprue – Celiac disease or Gluten enteropathy.Toxic effect from gluten present in grains has a direct destructive effect on intestinal enterocytes and destroys microvilli. This decreases the absorptive surface area by two fold.
Tropical Sprue - Mainly due to inflammation of the intestinal mucosa resulting form unidentified infectious agents and can be treated with antibacterial agents.
. As a result, the person suffers nutritional deficiency, osteomalacia due to lack of calcium, inadequate blood coagulation due to lack of vitamin K and macrocytic anemia owing to diminished vitamin B12 and folic acid absorption. |
|
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Term
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Definition
| The fat that appears in the stools is in the form of salts of fatty acids rather than undigested fat indicating the problem is absorption but not digestion. |
|
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Term
| Hartnup Disease (Neutral Amino Aciduria) |
|
Definition
genetic disorder->inability of intestinal and renal epithelial cells to absorb neutral amino acids from the lumen.
->excrete AA in urine, pellagra like features
Peptides still absorbed normally. |
|
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Term
|
Definition
Cause diarrhea. Cholera toxin ADP-ribosylates the Gs protein in the activation of cAMP cyclase to produce large amount of cAMP which causes efflux of water and electrolytes. Patients depleted of sodium.
Treatment: A practical use of the co-transport system of glucose uptake in intestine is the administration of a mixture of NaCl and glucose solution by mouth. |
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Term
| Pyruvate Kinase Deficiency |
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Definition
All deficiencies in glycolytic enzymes result in hemolytic anemia. Pyruvate kinase deficiency is the most common among this group.
Genetic defects lead to thermal liability, increased Km for phosphoenol pyruvate and decreased activation by F-1,6-bisphosphate.
Patients adapt by increasing 2,3 bisphosphoglycerate in their red blood cells to promote oxygen delivery. |
|
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Term
| glucose-6-phosphate dehydrogenase deficiency |
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Definition
| most common cause of hemolytic anemia |
|
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Term
| Fructosuria and Fructose Intolerance |
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Definition
High concentrations of fructose promote high levels of F-2,6-BP synthesis which inhibits gluconeogenesis.
If lack fructoskinase, fructose cannot be processed and accumulates in urine (benign)
Lack of aldolase B-> buildup of F-1-P (toxic- can lead to hepatic failure, hypoglycemia, death, etc.) |
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Term
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Definition
| Uridyltransferase deficiency. Accumulation of galactose-1-phosphate and galacitol in nerve, lens, liver and kidney tissue. Liver damage, mental retardation, and cataracts result. |
|
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Term
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Definition
| Normally catalyzes galactose->galactose-1-phosphate. Deficiency-> galacitol accumulation |
|
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Term
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Definition
| physiologically unimportant in galactose metabolism unless gal levels very high. Then deficiency->high levels of galacitol-> cataracts |
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Term
| Deficiencies in carnitine metabolism |
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Definition
decreased ability of tissue to metabolize long chain fatty acids. This causes the accumulation of toxic amount of free fatty acids and branched-chain acyl CoA in cells.
Syndromes include hepatic damage,
cardiomyopathy, muscle weakness, hypoketotic hypoglycemia.
Treatments include carnitine
supplementation, high carbohydrate feeding and avoid fasting. |
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Term
| Enzymes needed to oxidize unsaturated fatty Acyl coA |
|
Definition
propionyl coA carboxylase, methylmalonyl CoA mutase, reductase and isomerase (<-these 2 not needed for sat. fatty acyl coA)
isomerase-odd numbered double bonds
isomerase and reductase-even |
|
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Term
| flavoprotein dehydrogenase |
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Definition
| transfers electrons to O2 to form H2O2. The process reduces the long chain fatty acyl CoA to medium chain length (C6-10) acyl CoA for mitochondrial b-oxidation. |
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Term
|
Definition
| When b-oxidation is impaired, fatty acids are oxidized, one carbon at a time from the w-carbon by microsomal cytochrom P450-dependent hydroxylases and dehydrogenases. The product of w-oxidation is bicarboxylic acids which are substrates for peroxisomal b-oxidation of very long chain fatty acids. The final products of this process are 6-10 carbon dicarboxylic acids excreted into urine |
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Term
|
Definition
), high fatty acid degradation produces excessive amounts of actyl CoA. It increases NADH and slows down the TCA cycle.
The result is an increase of ketone body production that leads to ketonemia in blood and ketonuria in urine.
ketone has pKa=4 lowers blood pH
dehydration |
|
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Term
|
Definition
| an intermediate in fatty acid biosynthesis in cytosol. inhibits the “Carnitine Shuttle” by binding to CPTI and in turn controls the b-oxidation of fatty acid in mitochondria. ensures that biosynthesis and degradation of fatty acids will not occur at the same time in the cell. |
|
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Term
| citrate relationship to fatty acids |
|
Definition
| produced from TCA cycle and stimulates fatty acid synthesis in cytosol. |
|
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Term
| Carnitine deficiency and disorder with carnitine shuttle (CPT) |
|
Definition
| shows elevated blood free fatty acid and low fasting ketone production. Carnitine shuttle disorder results to increase acyl-carnitine in serum. Clinical syndromes include muscle aches and weakness following exercise and nonketotic hypoglycemia since gluconeogenesis cannot be supported by fat oxidation. |
|
|
Term
| Medium-chain acyl-CoA dehydrogenase deficiency |
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Definition
| long chains oxidzed to medium chain then stops. non-ketotic hypoglycemia symptoms if individual is fasting extremely, otherwise no symptoms apparent. |
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