Cells Flashcards
Alcohol fermentation?
Pyruvate -> acetaldehyde (using pyruvate decarboxylase)
Acetaldehyde -> ethanol (using alcohol dehydrogenase, forming an NAD+)
Lactate production?
Pyruvate -> lactate (using lactate dehydrogenase, forming an NAD+)
Acetyl CoA production from pyruvate?
Pyruvate + HS-CoA -> acetyl Co + CO2 (using pyruvate dehydrogenase complex, forming an NADH).
Acetyl group joins CoA group by high energy thioester bond which is readily hydrolysed so acetate can be donated to other molecules.
Thiamine pyrophosphate a co-factor of PDC, deficiency in thiamine = Beri Beri
Useful products from TCA with steps?
Isocitrate -> a-ketoglutarate (NADH)
a-ketoglutarate -> succinyl Co-enzyme A (NADH)
succinyl Co-enzyme A -> succinate (GTP)
succinate -> fumarate (FADH2)
maltate -> oxaloacetate (NADH)
overall 3NADH, 2CO2, 1GTP, 1FADH2
Solubility of enzyme in TCA?
All soluble and in mitochondrial matrix apart from succinate dehydrogenase which is insoluble and in inner mitochondrial membrane.
Products from glycolysis and steps?
- Glucose -> glucose-6-phosphate (ATP -> ADP + Pi).
- Fructose-6-phosphate -> fructose-1,6-bisphosphate (ATP -> ADP + Pi, enzyme phosphofructose kinase is rate limiting enzyme).
- GLAP -> 1,3Bisphosphoglycerate (2NAD+ -> 2NADH, GLAP dehydrogenase [redox and group transfer]).
- 1,3Bisphosphoglycerate -> 3-phosphoglycerate (2ADP -> 2ATP, phosphoglycerate kinase).
- Phosphoenolpyruvate -> pyruvate (2ADP -> 2ATP, pyruvate kinase, group removal).
net gain of 2ATP, 2NADH and 2pyruvate
Degradation of all 20 amino acids gives rise to?
Pyruvate
Acetyl CoA
Acetoacetyl CoA
Alpha-ketoglutarate
Oxaloacetate
Succinyl CoA
Fumarate
Example Transamination?
Alanine + a-ketoglutarate -> pyruvate + glutamate
C3 alanine undergoes Transamination by action of enzyme alanine aminotransferase.
glutamate can return to a-ketoglutarate using glutamate dehydrogenase
Warburg effect?
Mutations in genes of fumarase, succinate dehydrogenase or isocitrate dehydrogenase, decreased TCA activity, increases anaerobic glycolysis and preference to lactate production.
Glycerol phosphate shuttle?
DHAP -> G3P (NADH -> NAH+, using cytosolic glycerol-3-phosphate dehydrogenase)
G3P -> DHAP (FAD -> FADH2, using mitochondrial glycerol-3-phosphate dehydrogenase)
Electrons from FADH2 passed onto Co-enzyme Q -> QH2, part of ETC.
skeletal muscle and brain
Malate-aspartate shuttle?
Aspartate -> oxaloacetate -> malate (using aspartate transaminase and malate dehydrogenase, NADH -> NAD+)
malate through antiporter
Malate -> oxaloacetate -> aspartate (NAD+ -> NADH in mitochondria)
aspartate back through antiporter into cytoplasm
Transamination reaction in MAS - oxaloacetate + glutamate -> a-ketoglutarate + aspartate
in liver, kidney and heart
Fatty acid -> fatty acyl CoA?
Fatty acid + Coenzyme A -> fatty acyl CoA + H2O (acyl-CoA synthetase, ATP -> AMP +PPi)
in outer mitochondrial membrane
Carnitine shuttle?
Carnitine -> acyl carnitine (acyl CoA -> CoA, carnitine acyltransferase I)
carnitine through translocase into mitochondrial matrix
Acyl carnitine -> carnitine (CoA -> acyl CoA, carnitine acyltransferase II)
carnitine through translocase into cytoplasm
gets acylCoA into mitochondrial matrix for beta oxidation
Acyl CoA -> Acetyl CoA?
Oxidation, hydration, oxidation, thyolysis.
Per cycle, 1 FAD, 1NAD+ and 1 H2O used up.
1 Acetyl CoA, 1FADH2, and 1 NADH made.
Enzymes used in beta oxidation?
Short chain acyl-Coenzyme A dehydrogenase - anything less than 6C
Medium chain acyl-Coenzyme A dehydrogenase - 6C-12C
Long chain - 13C-21C
Very long chain - >22C
Ketone bodies from acetyl CoA?
Acetoacetone, acetone, D-3-hydroxybutyrate
Lipogenesis?
Enzymes - acetyl CoA carboxylase, fatty acid synthase.
1. Condensation (decarboxylative condensation, reaction of acetyl CoA + malonyl CoA, elongation)
2. Reduction (by ketoreductase)
3. Dehydration (by dehydratase)
4. Reduction (by enol reductase)
growing fatty acyl group linked to acyl carrier proteins
in adults, only in liver, lactating breasts and adipose tissues
Beta oxidation vs fatty acid synthesis?
Beta oxidation carrier is CoA, fatty acid synthesis is ACP.
Reducing power in beta oxidation is FAD/NAD+, in fatty acid synthesis is NADPH.
Location of beta oxidation is mitochondrial matrix, fatty acid synthesis is cytoplasm.
elongation of acyl group into fatty acids longer than 16C occurs in mitochondria and endoplasmic reticulum instead of cytoplasm
desaturation of fatty acids needs fatty acyl-CoA desaturases
Metabolic poisons?
Cyanide and azide - bind with high affinity to ferric form of haem group in cytochrome oxidase complex (IV), blocking final step in ETC.
Rotenone - inhibits transfer of electrons from NADH dehydrogenase (I) to ubiquinone.
Oligomycin - binds to ATP synthase and blocks flow of electrons through enzyme.
Malonate - resembles succinate, competitive inhibitor of succinate dehydrogenase (II). Inhibits oxidation of succinate -> fumerate, so slows flow of electrons from succinate -> ubiquinone.
DNP?
Dinitrophenol - proton ionophore, shuttles protons across inner mitochondrial membrane, uncouples oxidative phosphorylation from ATP synthase. Increases metabolic rate and temperature so weight loss.
Cell cycle phases?
G1 - decision point (interphase)
S - DNA replication (interphase)
G2 - decision point (interphase)
M - mitosis and cytokinesis, most vulnerable period, gene transcription silenced.
G0 - quiescent phase, cell cycle machinery dismantled, stays until triggered externally to G1
cyclical due to degradation and reformation of cyclins
Signalling cascade?
Growth factors, signal amplification, MAP kinases.
Mitogen activated protein kinases - Ras, Raf, MEK, ERK. Increase protein synthesis + decrease protein degradation.
cMyc?
Oncogene
Induced by growth factor signalling
Promotes G0 -> G1 and increases concentration of Cyclin D.
Cdk?
Cyclin dependent kinases, regulated by interactions with cyclins and phosphorylation. Cdk 1, 2, 4 +6.
phosphorylate + dephosphorylate serine, threonine and tyrosine
sequentially activated + stimulate synthesis of genes for next phase, giving direction and timing