Fundamentals 1 Flashcards
Type 1 Diabetes
No insulin is made (pancreas is attacked – autoimmune disorder, potentailly) no insulin produced in pancreatic beta cells -> liver acts as if body is always in starvation state -> hyperglycemia plus gluconeogenesis, limited glucose uptake in muscle/adipose - also ketone bodies are produced (liver thinks it is starved because there is no insulin) – DKA w/out insulin
Type 2 Diabetes
Insulin level are normal:
Receptor defects
Processing
Reduced Kinase Activity
Immune system defects
Type A : antibodies to insulin. No free insulin available to bind to receptor
Type B : antibodies to insulin receptor, such that either insulin binding is blocked, or the antibody itself is stimulatory
Obesity related diabetes (down-regulation of insulin receptors; related to metabolic syndrome
IV fructose
low phosphate/Energy
elevated uric acid, lactic acidosis
Hypoglycemia
Lots F1P
essential fructosuria
fructosekinase can’t phosphorylate fructose
Hereditary fructise intolerance
no aldolase B, F1P backs up and inhibits glycogen phosphorylase; no degradation
can’t have fructose
low phosphate/Energy
high uric acid / lacitc acidosis
hypoglycemia (F1P inhibits the Glycogen Phosporylase)
(this often present when a child switches from breat milk to juice, resulting in hypoglycemia)
lactase deficiency
bad lactase
can’t have lactose, diarrhea, flatulence, stomach pain
classical galatosemia
no gal-1p uridylyl transferase
high blood galatose and galatitol – cataracts and mental retardation; hypoglycemia (note: gal-1P looks like G1P so no degrdation of G1P into glucose will occur)
nonclassical galactosemia
no galactokinase
high blood galactose/galactitol; cataracts (less severe than classical galactosemia as the nervous sytem is uneffected)
pyruvate kianse deficiencey
sugar enzyme (converts phosphoenol pyruvate to pyruvate producing an ATP
no pyruvate made
Hemolytic Anemia – not a great enough energy supply for the RBC
pyruvate dehydrogenase deficiency (Leigh Syndrome)
sugar enzyme – connecting glycolysis to the TCA cycle converting pyruvate into acetyl-CoA
no Acetyl-CoA made
LEthargy
Neuro Problems, Seizures
Poor Muscle Tone
Ataxia
TCA/OxPhos disease
mitochondrial/nuclear genome
muscle/nerve problems
Primary Carnitine Deficiency
lack of/defective membrane carnitine transporter (translocase) prevents carnitinve entry into cells, unable to transport FAs into mitochondria to make energy — causes weakness, cramping, fasting hypoglycemia,Triacyl-Glyeride accumulation in the muscle/liver cytoplasm (DHAP pathway), elevated Urine carnitine levels
might be treatable with axogenous carnitine to overcome the higher Km of the transporters
Secondary Carnitine Deficiency
defect in Carnitine-Acyl-Transferase-2 (CAT 2 or CPT 2), the carnitine cannot be removed from the FA inside the mitochondrai. Therefore the carnitine is stuck within the mitochondria bound to the FA and there is no free Carnitine. Therefore FA oxidation is blocked. This causes muscle weakness, cramping, fasting hypoglycemia, triacyl-glycerol accumulation in msucle/livercytoplasm; we ill also see elevated serum acyl-carnitine levels
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
fatty acid enzyme disease – displayed in elevated 6-10 carbon dicarboxylic acids, hypoketotic, hypoglycemic when glycogen stores are low – functions to break down medium chain fatty acids 8-12 carbons long (This is all a result of a point mutation in which Glu si change to Lys, changing the charge of teh amino acid, therefore destabiulizing the protein causing it to have an altered function.)
dicarboxylic acids build up; fasting hypoglycemia
Glucose-6-Phosphate dehydrogenase Deficiency
Enzyme for the HMP pathway which produces NADPH is lacking, Glutathione not replinished
X-linked, hemolytic anemia (bursting RBCs)
Adenosine deaminase deficiency (ADA)
severe combined immunodeficiency (SCID)
nucleotide salvage
no immune system cells (B or T cells)
Pneumonia, Diarrhea, Skin Rashes
Gout
to many purines
uric acid builds up; crytals resulting in inflammation
Reduce Purine Intake. Don’t eat liver. Also, Allopurinol is a Xanthine Oxidase Inhibitor which blocks the production or uric acid
Lesch-Nyhan Syndrome
nucleotide salvage
missing hypoxanthine guanine phosphoribosyltransferase 1 (HGPRT) – can’t salvage hypoxanthine/guanine
Neuro symptoms
Mental Retardation, Self-Mutilation
Hereditary Orotic Aciduria
pyrimidine synthesis problem
Missing UMP synthase (Orotic phosphoribosyl transferase + OMP decarboxylase)
Retarded growth, anemia and excessive urinary excretion of orotic acid
hyperammonemia
AA metabolism –> Often a urea cycle problem
ammonia in the blood
Elevate ammonia in the blood which can lead to several complications, including neurological problems
PKU (PhenylKetoUrea)
henylalanine cannot be converted –> Tyrosine
Phenylalanine Hydroxylase
Mental Retardation, Behavioral Problesm, Seizures, Hyperactivity, stunted growth (microcephaly) and skin rashes
Maple Syrup Urine Disease (MSUD)
leucine, isoleucine, valine
Bracnched Chain Amino Acids are Trans-aminated, but not carboxylated
Urine Smells like Maple Syrup
Damage to the Brain can occur during times of high physical exertion (exercise, fever, infection)
tyrosinemia
tyrosine
Delayed Enzyme maturation in the catabolic tyrosine
Homocysteinemia
methionine synthase, N5-N10TF reductase, B-Cystathionien synthase
Also from B12, Folate and B6
atherosclerosis – promotes plaques (increases smooth muscle growth, while decreasing epithelial tissueg rwoth)
Thrombosis (because homocysteine interfers with the clotting cascade)
pallegra
Missing nicotinomide (niacin)
No NAD+; 4 D’s: dermatitis, dementia, diarhea, death
Cholera
Toxin blocks Gs
constant activation of the G-protein cascade
Diarrhea
Pertussis
toxin blocks Gi
no Inhibition of G-protein cascade
BerBeri (Overview) – frequent in alcoholics as they do not absorb Thiamine well
B1 deficiency, no Thiamine; problems with TK, PDH, aKGDH
enzymes don’t work –n o decraboxylation (E3)
Wet: heart, edema, cofusion, nystagmus
Dry: peropherial neuropathy
Wernicke Korsacoff (Dry BeriBeri)
Thiamine deficient from alcohol
Neural disfunction: nystagmus, edema, confusion, ataxia (random movememnts)
Drug Tolerance
Increased cycP450 activity
Drugs clear faster
Aspirin Over Dose
run out of NADPH to reduce glutathione to neutralize the toxin
Barbituate toxic
ethanol mixed will inhibited cycP450
Familial Lou Gherig’s (ALS)
no superoxide dis mutase – radical O2 species destroy tissues, genetic origin
slow break down of nerves/muscles
MODY (maturity onset diabetes of the young)
no glucokinase in pancreaseb eta-cells; no ATP;potassium channel does not stop, therefore calcium does not enter the cells, no insulin is produced by the pancreatic Beta-Cells.
B6 deficiency (pyridoxyl phosphate)
no phosphorylase, no glycogen breakdown, no homocysteine breakdown
Arsenic Poisoning
Arsenic targets lipoic Acid
no PDH, aKGDH, garlic breath, rice water stool and vomiting
no activity of: phosphoglycerate kinase or glyceraldehyde-3-phosphate dehydrogenase
Malonate
competes with succinate for succinate dehydrogenase interfering with fumurate production
Low fumarate
Fluoroacetate
blocks aconitase
low isocitrate (citrate build-up, slowing glycolysis and promoting FA production)
Oligomycin
blocks F0 channel of ATP synthse
DCCD
DCCD
thermogenin (natural for heat in babies and some animals)
Uncoupler, destroys the hydrogen ion gradient
weight loss, warmth, no energy, death if great amount
weight loss, warmth, no energy, death if great amount
Uncoupler, moves potassium ions, destroys the gradient
dinitrophenol (diet pill)
Uncoupler
Rotenone
No Fe-S to CoQ in complex 1
Antimycin A
Cytochrome C can’ta ccept electron, complex 3
Cyanide/C=O
no Fe binding in complex 4`no Energy
Atractyloside
no ATP leave, no ADP
