Pathways Biochem

arne1's version from 2015-09-16 21:43


Question Answer
GLUT transport glucose into blood viafacilitated diffusion
GLUT1 in erythrocytes
GLUT2in liver
GLUT1 and 3in neurons and brain
GLUT 4in adipose tissue and muscle responsive to insulin. More GLUT4 with high insulin and blood sugar
Glucose is phosphorylated to Glu-6-phosphate. by either glucokinase or hexokinase
glucokinasein liver (high Km - low affinity for glucose). needs high glu concentrations to be more active.It has a high vmax. also present in beta cells of pancreas.
High Km meanslow binding affinity
Hexokinasepresent in all tissues. low Km (high affinity for glucose). also has a low vmax.
Glu-6-phosphate can be converted toGlycogen, Pyruvate, HMP shunt
1 glucose yields2 Pyruvate, 2 ATP, 2 NADH
Glucose to G-6-PIrreversible step
Phosphofructokinase-1 (PFK-1)Fructose 6-phophate to Fructose 1,6-bisphosphate. allosterically regulated. irreversible step
Aldolase Ain muscle
Aldolase B in liver
In anearobic respiration, high NADH/NAD+ favorslactate formation (as opposed to pyruvate)
Aerobic glycolysis nets8 ATP, end product ins pyruvate --> ACoA
anearobic glycolysis nets2 ATP, end product is lactate via LDH
Arsenateinhibitor of glycolysis. inhibits glyceraldehyde 3-phosphate dehydrogenase. no 1,3-bisphosphoglycerate and no NADH formed.
Flourideinhibitor of glycolysis. inhibits Enolase. no Phosphoenolpyrivate is formed. in labs, blood is collected in floride to get an estimate of blood glucose (levels would otherwise be refuced by RBSs and WBCs)
in blood, anearobic glycolysis forms: 2,3 BPG --> right shift
hemolytic anemiaerythrocyte pyruvate kinase deficency (no formation of pyruvate and ATP) -->Na/K ATPase is compromised --> osmiotic imbalance (high Na in RBC) --> lysis.
Lactic acidosispH low, Serum HCO3 decreased, PO2 decreased during compensation. Causes: incr NADH/NAD+ ratio --> conversion of pyruvate to lactate. dehydrogenase deficiency (Leigh disease). Thyamine deficiency (low activ of pyr dehydroganase), defect in gluconeogenesis, low blood supply, high activity.
cancer cells energy sourceglycolysis for ATP (Warburg effect). Glucoce analog, ‘fluorodeoxyglucose (FDG) is taken up by cancer cells. Can visualize with PET.
Hypoxia and tumor cellshypoxia activates HIF-1 --> blod vessels grow. Glycolytic enzymes in tumor increase.
bifunctional enzymehigh insulin --> PFK2 dominant --> makes Fru2,6-bisphosph --> allosterically activates PFK-1 (glycollysis). With glucagon (low blood glucose) -->phosphorylated-->fructose 2,6 bisphosphatase active -->decreased levels of Fructose 2,6- bisphosphate, that allosterically activates Fructose 1,6- bisphosphatase (gluconeogenesis)
Activators of PFK-1 (glycolysis)high AMP, high activity, high Fructose 2,6-bisphosphate, high blood glucose
inhibitors of PFK-1 (pevent glycolysis)resting, high ATP, low Fructose 2,6-bisphosphate, low blood glucose.
Role of fructose 2,6-bisphosphatestimulates glycolysis - stimulation in liver
Mito matrix is site of Pyruvate oxidation, TCA cycle, beta oxidation of fats, etc...
CoA is derived from Vitamin B5
NAD+ is derived fromniacin (Vit B3)
FAD is derived from vitamin B2
Pyruvate dehydroxygenase (PDH) is activated bydephosphorylation, insulin, catecholamines (cardiac muscle), Ca+ in skeletal muscle, Mg++ - activate PDH phosphatase
PDH is inhibited byACoA, ATP, NADH - act via inhibition of PDH kinase
Phosphorylated PDH is inactive
ACoA can come fromGlycogen (glycogenolysis), Triglicerides (lipolysis), Protein (proteolysys). All undergo oxidation.
ACoA fatesTCA cycle, Ketone bodies, Sterols - fatty acids.
in TCA cycle isocitrate dehydrogenase is activated by ADP and Ca++, and deactivates by ATP and NADH
in TCA cycle alpha ketoglutarate is activated by Ca++ and deactivates by ATP, GTP, NADH, Succinyl CoA.
Yield of TCA cycle (one revolution)3 NADH (9 ATP), 1 GTP (1 ATP), 1 FADH2 (2 ATP). Total of 12 ATP per ACoA oxydized and 24 ATP per glucose.
Four regulated enzymes in TCACitrate Synthase, Isocitrate dehydrogenase, alpha-KG dehydrogenase, succinate dehydrogenease
Activation of citrate synthaseCa+= and ADP, nhibited by ATP, NADH,succinyl CoA and Fatty Acyl CoA
Activation of Isocitrate DehydrogenaseADP and Ca++, inhibited by ATP, NADH
Activation of alpha-KG dehydrogenaseCa++, inhibited by ATP, GTP, NADH, succinyl CoA
Activation of succinate dehydrogenaseADP, Pi, succinate, inhibited by OAA
NADH shuts downconversion of Pyruvate to ACoA. ACoA itself inhibits this conversion.
Total energy yield per glucose molecule 8 ATP for glycolysis, 30 in mitos (36-38 total)
Pyruvate dehydrogenase deficiencyhigh pyruvate --> high lactic acid and alanine, low ACoA and low ATP. Leads to lactic acidosis, neuro defectsm myopathy (fatal)
Werneke-Korsakoffthiamine (PDH coenzyme). Ataxia, Ophthalmolplagia,Memory loss, Cerebral Hemorrhage. At risk are alcoholics and malnourished individ. Heart failure, low ATP, increased cardiac output (wet beri-beri)
Arsenic poisoningbinds to lipoic acid (needed for the activity of dihydrolipoyl transacetylase (E2) - part of the PDH complex). --> lactic acidosis, neuro defects, death.
Inhibitor of aconitaseflouroacetate
ihibitor of succinate dehydrogenasemalonate
Leber's hereditary optic neuropathy (mito disease)defect in NADH dehydrogenase (ETC)
The ETC oxidizesNADH and FADH2
ETC happens oninner membrane of mitos (make ATP from ADP using energy from NADH and FADH2)
PDH and TCA happens inmatrix of mitos
ETC complex INADH dehydrogenase (contains iron-sulfur proteins) - prosthetic groups are FMN and FAD
ETC complex IIsuccinate dehydrogenase (contains iron-sulfur proteins) - prosthetic groups are FMN and FAD
ETC complex IIIcytochrome C reductase (contains iron-sulfur proteins) - preostethic group is heme (Fe3+)
ETC complex IVcytochrome Coxidase - prosthetic groups are Cu2+ and Fe3+
ETC - Protons are pumped into intramembrane space at complexesI, III, IV
Complex V isATP synthase. protons come run through it into the matrix and ATP is produced. (oxidative phosphorylation)
NADH dehydrogenase in complex I is inhibited byRotenone (pesticide), piericidin A (bacterial antibiotic) and the barbituate amytal
cytochrome b of cytochrome reductase (complex III) is inhibited byAntimycin A
Cytochrome oxidase (complex IV) is inhibited byCO, azide, Hydrogen Sulphide (H2S) and cyanide (CN-)
ATP synthase is inhibited byOligomycin (a streptomyces antibiotic)
ETC inhibitors effectdecrease ATP snthesis, decrease ETC and O2 consumption
Adenine nucleotide translocaseantiport of ATP for ADP
ADP/ATP transport is inhibited byatractyloside (thistle plant); bongkrekic acid (resp toxin in coconuts) (both have similar effects to oligomycin).
ETC uncouplersDNP (dinitrophenol), ASA (Aspirin), thermogenin, ionophores - all destroy the proton gradient.
Function of ETC uncouplersdestroy the proton gradient. decrease ATP synthesis, increase ETC and oxygen consumption (O2 used but no ATP prduced). they punch a whole in the inner membrane, allowing protons to come into the matrix without creating ATP.
thermogenin (uncoupling protein - UCP)dissipation oh H+ gradient uncoupled from ATP synthesis generates heat. found in brown adipose tissue of babies. UCP can be hormonally induced.
ionophorestransport diff kinds of ions (uncouplers are specifi to protons)
Gramicidinionophore (antibiotic produced by bacillus brevis)
Valinomycinionophore. antibiotic from Streptomyces. carries K+
Shuttles that carry NADH across the inner mito membraneglycerol phosphate shuttle (2 mol ATP/NADH), malate-aspartate shuttle (3 mol ATP/NADH)
NADH produces3 ATP
FADH2 produces2 ATP (bypasses complex I of the ETC)
ETC is active whenADP>ATP and NADH>NAD+
Hypoxia and ETCO2 is final electron acceptor. H. decreases the rate of ETC and ATP production. more anerobic glycolysis --> lactic acid --> neural tissue and heart undersupplied --> MI --> tissue damage --> leakage of intracellular enzymes (CK1, CK2, LDH) and troponin I and T.