Hereditary Fructose Intolerance (HFI)
Defect in Aldolase B, accumulation of F-1-P. Symp: high blood fructose levels, fructosuria. Tx: remove fructose from diet
Fructokinase Deficiency, fructose cannot be phosphorylated in liver, but processed in muscle. Symp: increase  of fructose in urine.
Galactose 1-P Uridyl Transferase Defect/Deficiency, high cellular levels of Gal-1-P. Similar to HFI, but more tissues affected. Symp: Galactosaemia and Galactosuria. Tx: remove galactose from diet and therefore lactose
Galactokinase Deficiency, Causes galactosaemia and galactosuria. If galactose is present in the diet, galactitol can accumulate. Symp: Galactitol accumulation can cause cataracts (think sorbitol)
Glucose 6-phosphate dehydrogenase Deficiency (G6PD Deficiency)
Glucose 6-phosphate dehydrogenase Deficiency. NADPH deficiency leading to an inability to reduce glutathione among other things. SYMP: Hemolytic anemia.
Chronic Granulomatous Disease (CGD)
Defective NADPH Oxidase. Inability to produce superoxide anions. SYMP: recurrent life-threatening bacterial and fungal infections.
Ehlers-Danlos syndrome Classical type
Deficiences in collagen processing enzyme, mutant collage alpha chains. SYMP: All types affect joints and most affect skin. Flexible joints that extend beyond normal range, stretchy fragile skin, delayed wound healing.
Pyruvate Kinase deficiency
5-25% of pyruvate kinase activity, less than 5% is fatal, ATP is required for maintenance of Na+, K+ transporting. Cells dependent of glycolysis (RBCs) swell and lyse. SYMP: Severe anemia
Mercury and Arsenite poisoning
Both bind to dihydrolipoyl group of the pyruvate dehydrogenase complex. SYMP: CNS pathologies
AsO43- is an anion analogous to phosphate. Gets incorporated into glycolysis as a substitute for phosphate. Attaches to glyceraldehyde 3-phosphate making 1-arseno-3-phosphoglycerate. SYMP: Not much. Loses 2 ATP per glucose molecule.
is a potent inhibitor of enolase (by interfering with substrate binding). competitive inhibitor. Fluoride bears no resemblance to 2-phosphoglycerate (enolase substrate). But it binds to Mg++ and phosphate forming a complex at the active site
Thiamine deficiency. Cannot make thyamine pyrophostphate, coenzyme of PDH (E1). SYMP: Advanced neuromusclular and cardiac disorders: delirium, muscle weakness, memory loss, ophthalmoplegia, peripheral vasodialation, increased venous return to heart. Death by high output heart failure. Tx: eat thiamine! Rice husks.
Thiamine deficiency due to chronic alcohol abuse. Cannot make thyamine pyrophostphate, coenzyme of PDH (E1). SYMP: Initial stage: Wenicke's enchepalopathy: delirium, mental derangement, ataxia, and ophthalmoplegia. Late stage: Korsakoff's psychosis: anterograde amnesia and brain damage. eat thiamine! Rice husks. Late stage irreversible
Pyruvate Dehydrogenase deficiency
Pyruvate Dehydrogenase deficiency genetic defect of PDH E1. Cannot process pyruvate into Acetyl-CoA, therefore can't enter TCA, vital for brain function.
SYMP: Depends on extent of residual enzyme function. Low function: early onset of mental retardation, microcephaly, optical atrophy. Higher function: later onset, with progressive spinocellular ataxia. Both early death
Leber Hereditary Optic Neuropathy (LHON)
Mutation in NADH dehydrogenase gene (Complex I). Neuroretinal degeneration - optic nerve due to its high energy demand (oxidative phosphorylation). SYMP: Late onset loss of bilateral vision. EXTRA: Mitochondrial gene defect mother passes on to all offspring
Myoclonic Epilepsy & Ragged-red fiber disease (MERRF)
Mt genome mutation in the tRNA for LYSINE. Enlarged mitochondria, ragged red fibres in muscle tissue with clumps of mitochondria. SYMP: Uncontrollable muscle jerking (myoclonus). Epileptic sezures. Lactic acidosis, progressive dementia, cardiac problems. EXTRA: Mitochondrial gene defect mother passes on to all offspring
Mitchondrial Encephalomyopaty, Lactic Acidosis, & stroke-like episodes (MELAS)
Mt genome mutation in the tRNA for LEUCINE. Neurodegenerative disease, lactic acidosis, repeated strokes. SYMP: Stroke-like episodes lead to blindness, brain damage, dementia, loss of muscle control. Lactic acidosis symptoms (vomiting, tiredness, muscle weakness). EXTRA: Mitochondrial gene defect mother passes on to all offspring
Aminoglycoside Induced Deafness
Mutation in the 12s rRNA. Increased binding of aminoglycosides like streptomycin and gentamycin to 12s rRNA. Loss of translation of ATP synthase. SYMP: Cochlea has high energy demand=deafness.
Lysosomal Storage Disease (Lipid Storage disease), Sphingomyelinase deficiency - Inability to degrade sphingomyelin. SYMP: Enlarged liver and spleen filled with lipid, severe mental retardation and neurodegeneration, early death. Additional info: CHERRY RED SPOT IN RETINA! Type A and B (later in childood). Ashkenazi Jews carry defective gene.
Lysosomal Storage Disease (Lipid Storage disease), Hexosamindase A deficiency - Hereditary sphingolipid storage disease, problem with ganglioside GM2 breakdown. Additonal info: CHERRY RED SPOT IN RETINA!
FATAL neurodegenerative disorder, death between 10 - 15 yrs. Ashkenazi Jews carry defective gene.
Mutliple sclerosis (MS)
Deterioration of myelin sheaths due to autoimmune reaction. Forms scleroses.
ABC Transporter defect. ABC transporter moving cholesterol out of cell is broken. Not enough HDL in the blood stream. Tangerine tonsils.
ABC Transporter defect. ABC transporter broken, Bilirubin accumulates in body. SYMP: Jaundice
ABC Transporter defect, ABC transporter for to import enzymes and such into peroxisomes is broken. No peroxisomes.
ABC Transporter defect, ABC transporter that carries fat is broken. Can't make myelin.
ABC Transporter defect. Can't pump plant sterols back into lumen.
ABC Transporter defect, (genetic defect in CFTR gene - gene for chloride channel protein). Broken Cl- transporter - NaCl accumulates in the cell bringing water with it. Thick mucous in the lungs and obstruction of pancreatic ducts. Cholera is the opposite
von Gierke's Disease (TYPE I)
Defect in Glucose-6-phosphatase. Buildup of glucose-6-phosphate in liver and kidneys. Depletion of inorganic phosphate. SYMP: Hepatosplenomegaly, acidosis, ketosis, hyperlipidemia. DEVELOPS AFTER BIRTH!
Pompe's Disease (TYPE II)
Lysosomal glucosidase. SYMP: Cardiomegaly & heptomegaly. MUSCLE GLYCOGENOSES. DEVELOPS SEVERAL MONTHS AFTER BIRTH!
Cori's or Forbe's Disease (TYPE III)
Debranching Enzyme. SYMP: Hepatomegaly, normal blood glucose and lipids DEVELOPS AFTER BIRTH!
Anderson's Disease (TYPE IV)
Branching Enzyme. SYMP: Hepatosplenomegaly, cirrhosis & Liver failure
McArdle Disease (TYPE V)
Muscle Glycogen Phosphorylase. SYMP: Muscle weakness & Cramping, normal lactate MUSCLE GLYCOGENOSES. DEVELOPS IN LATE CHILDHOOD/EARLY ADOLESCENCE!
Hers Disease (TYPE VI)
Liver Glycogen Phosphorylase. SYMP: Hepatomegaly, less severe hypoglycemia than type 1, lipidemia or acidosis
Tarui's Disease (TYPE VII)
Muscle PFK-1 (muscle and erythrocytes). Muscle weakness & cramping during exercise. MUSCLE GLYCOGENOSES
Type 0 glycogen storage disease
Glycogen Synthase. SYMP: No glycogenesis, hypoglycemia.
Lysosomal Storage Disease (Lipid Storage disease), alpha-Galactosidase, accumulation of Ceramide trihexoside. SYMP: Angiokeratoma (red-purple skin rash), kidney failure, hypohidrosis (diminished perspiration), argoparethesias (pain/tingling in lower extremities)
Lysosomal Storage Disease (Lipid Storage disease), Glucocerebroside-β-glucosidase - Glucosylceramide accumulation in lysosomes, particularly in reticulendothelial system. SYMP: Splenohepatomegaly, erosion of longbones and pelvis, mental retardation only in infantile form
Generalized, gangliosidosis (GM1 gangliosidosis)
Lysosomal Storage Disease, β-Galactosidase
- Ganglioside GM1 accumulation SYMP: Mental retardation, hepatomegaly, skeletal deformaties
Hurler (MPS IH)
Mucopolysaccharidose, defect in α-L-iduronidase. Dermatan sulphate and heparan sulphate accumulate in the blood and urine. SYMP: Skin, soft tissue and subcutaneous cartilage thickened and stiff, nasal bridge is depressed, wide vertical bony ridge in forehead, teeth widespread and poorly formed, corneal clouding, deafness, hydrocephaus Tx: Future treatment options: stem cell, enzyme infusion therapy.
Accumulate of: Dermatan sulfate and heparan sulfate
Hunter (MPS II)
Mucopolysaccharidose, defect in Iduronate sulphatase. Dermatan sulphate and heparan sulphate accumulate in the blood and urine. SYMP: Hurler-like, but less severe. Presents 2-5 years. Hepatosplenomegaly
Tx: Enzyme infusion therapy has been successful reducint hepatosplenomegaly.
Accumulate of: Dermatan sulfate and heparan sulfate
Body makes antibody to centromeres
Osteogensis imperfecta (TYPE I)
COLI1A1 and COL1A2 mutations. >400 causing mutations have been identified. Bone fractures during childhood due to minor trauma, blue grey tint in sclera.
Osteogensis imperfecta (TYPE II Congentia)
COLI1A1 and COL1A2 mutations. Affected individuals die in utero. Prevention of triple helix formation as Gly replaced by amino acids possesing bulky side chains.
Vit C deficiency. Subcutaneous extravascation of blood due to capillary fragility.
Defects in fibrillin gene. SYMP: changes in elastic tissue particulary in the aorta, eye and skin. Overgrowth of the long bones of the body. DON'T HAVE STRETCHY SKIN!
Cholestrol gall stone disease, Equilibrium between the cholestrol entering the bile and bile salts present is disturbed. Tx: Surgery: Cholecystectomy, Extraneous bile salts: chenodeoxylic acid
Bile acid sequestrant. Bind bile acids and prevent their reabsorption from the gut cause excretion of bile acids from the body. Used in treatment of hypercholesteroemia
Hereditary pancreatitis may be due to a genetic abnormality that renders trypsinogen active within the pancreas, which in turn leads to digestion of the pancreas from the inside.
Steatorrhea/Malabsorption of fats
Excessive lipid in feces
Liver - impaired synthesis of biles acids and salts
Gallbladder - imparied release of bile ex. Gall stones
Pancreas - decrease in the release of pancreatic lipase ex. CF
Intestional cells - Defects in absorption of fats ex. Sprue
- Primary lactose intolerance: decrease in activity of lactose from childhood to adulthood
- Secondary lactase deficiency: chronic severe diarrhea, intestinal disease
Presece of reducing sugars in stool
thinning of hair
Tx: protein in diet
Increased levels of uric acid in blood lead to its precipitation forming Na+ urate crystals
which are deposited in in kidney and joints
Damage to mucosal layer - acid can attack the stomach lining, causing erosin and ulcers
h. Pylori infection
excess gastric secretions - gastrinoma
I -cell disease
Due to a deficiency of the mannose-6-P marker, Mucopolysaccharide and glycolipid accumulate
Barth syndrome (BTHS)
Respiratory Distress (RDS)
Associated with lung surfactant. Decreased lung compliance, hypoaxemia Dipalmitoylphosphatidylcholine (PtdCho) is the main component responsible for lowering lung surface tension. Premature babies have underdeveloped lungs which lack normal amounts of ant.
Low levels of L-dopa.
L-Dihydroxyphenylalanine (L-dopa) is an intermediate in epinephrine synthesis.
Regulating sleep and emotional state
Insuffecient serotonin synthesis may be one cause of clinical depression.
Prozac (fluoxetine) is an antidepressant drug that blocks serotonin elimination from synaptic cleft.
Manic depression....very high levels of serotonin.
Lysergic acid diethylamide (LSD)
Blocks serotonin receptors that are located in the brain stem
If histidine loses its acidic group, histamine is formed (potent vasodilator).
Histamine is released as part of the immune response increasing delivery of white blood cells.
Results in swelling & stiffness..... Cold symptoms
Cold symptoms are alleviated by anti-histamines eg. Benylin.
γ-Aminobutyric acid (GABA)
is the chief inhibitory neurotransmitter in the mammalian central nervous system
It plays a role in regulating neuronal excitability throughout the nervous system
In humans, GABA is, among other things, directly responsible for the regulation of muscle tone.
Porcine, bovine and human insulin
Different primary structures
Possible allergic response to porcine form
Porcine insulin is closer in structure to humans than bovine. Must know the structure of insulin (A and B chains linked via intramolecular disulphide bridge (51 a.a. In primary structure).
Protein folding disease (conformational disease)
Characterized by the accumulation of malformed protein that aggregate intra-cellularly and extra-cellularly. Protein deposits are known as amyloids (disease as amyloidosis). α-Helices are replaced by β-pleated sheets, and the resultant protein aggregates are proteolytic resistant.
Prion disease (protein misfolding disease)
Neurodegenerative disorders that affect animals and humans. Known as transmissible spongiform encephalopathies. Scrapie (sheep & goats), mad cow disease and Kuruwere once believed to have been caused by slow viruses.
Glycosylated hemoglobin levels, specifically the HbA1c fraction determine whether blood sugar levels have been successfully controlled over the previous few months. Measuring HbA1c helps to assess the quality of long-term metabolic control in treated diabetic patient
Extent of Hb glycosylation is a direct reflection of the average serum glucose concentration to which the cell has been exposed over its 120-day lifespan.
SYMP: Fatigue/cold intolerance, reduced O2supply, reduced heat production, paleness
Eg. Pernicious anaemia(biogenesis of RBC... lack of B12
internal bleeding e.g. bleeding womb ulcer
Premature rupture of cell membranes
Paget's disease of the skull
Typical face is referred to as a "faciens leotina".
Increases in this enzyme are indicative of bone diseases. Alkaline phosphate (ALP) spilling into blood.
Diisopropylfluorophosphate = nerve gas (DFP)
Irreversible inhibitor, OH group of Serine
Blood cholesterol can be lowered by administering a statin that inhibits cholesterol synthesis
ex. Lovastatin (competitive inhibitor)
Angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of congestive heart failure.
Captopril --> inhibits competitively ACE --> Decreased plasma angiotensis II levels --> Vasoconstriction by angiotensis II blocked --> Blood pressure decreases.
Drug used primarily to treat hyperuricemia (excess uric acid in blood plasma) and its complications, including chronic gout. Irreversible suicide inhibitor of xanthine oxidase.
A bit opposite of Cystic Fibrosis, excretes Cl- out of cells, massive loss of ions and water in faeces
modifies G proteins. Cells flooded with cAMP causing profuse secretion of electrolytes with subsequent water loss.
Hyperglycaemia, sorbitol metabolism (Polyol pathway)
Hyperglycaemia leads to elevated intracellular glucose levels in such tissues, leading to sorbitol production (trapped) via the polyol pathway. Excess sorbitol increases osmotic effects (swelling). involved in cataract formation.
Aversion therapy for alcoholics.
alcohol --> acetaldedyde --> acetic acid
Aldehyde dehydrogenase has an active site cysteine residue that is irreversibly modified by Disulfiram.
Acetaldehyde accumulates in tissues causing vomiting, hopefully leading to alcohol avoidance by alcoholics.
Initial symptoms of MeOH poisoning include impaired vision. MeOH slowly metabolised to formaldehyde by alcohol dehydrogenase which is then further (rapidly)metabolised to formic acid (metabolic acidosis). Tx:
bicarbonate & hemodialysis
Ethylene glycol poisoning (Antifreeze)
Absorbed by GI tract, metabolised by liver
alcohol dehydrogenase converts it to glycoaldehyde