Enzymes/Coenzymes/Inhibitors/Activators Flashcards
Other name for Acetyl CoA
Pantothenic Acid
Hydrophilic carboxyl group of Facid. Ionized at what pH
pH 7
Substrates/Products Citrate Synthase
Substrate: OAA + Acetyl Coa
Products: Citrate & Coa
Substrate/Products/Coenzymes ATP-citrate lyase
Substrate: Citrate & ATP & Coa
Products: OAA & Acetyl Coa & ADP+Pi
Prosthetic of ACC
Biotin. & Adds CO2 to methyl end of Acetyl CoA
Acetyl Coa Carboxylase: Substrate/Products
Substrate: Acetyl Coa & ATP & Co2
Products: Malonyl & ADP + Pi
Short-term allosteric regulation of acetyl CoA carboxylase
Citrate shifts the polymer - dimer equilibrium towards polymer formation. Activation
Palmitoyl CoA shifts the equilibrium towards dimer formation. Inhibition
Short-term hormonal regulation of acetyl CoA carboxylase
Glucagon, epinephrine, and norepinephrine trigger a cAMP dependent phosphorylation of the enzyme (through activation of AMPK) that shifts the equilibrium towards dimer formation (inactive form).
Long-term regulation of acetyl CoA carboxylase
- high carbohydrate and fat-free diets lead to increased synthesis of ACC (up-regulation, induction) resulting in increased synthesis of FA
- high-fat diets, fasting and glucagon lead to decreased synthesis (down-regulation, repression) resulting in decreased synthesis of FA
Enzyme the hydrolyse Palmitoyl-ACP in order to form free Palmitoyl
Thioesterase
Activation Fatty Acid: Substrates, Products, Enzymes
Substrates: Fatty Acid + CoASH + 2ATPs
Enzyme: Fatty Acyl Coa Synthetase
Products: Fatty Acyl Coa + AMP + PPi(–>2Pi)
Systemic fatty acid oxidation disorders
Organs, Symptoms, Causes
Organs: Liver, Muscle
Symptoms: Hypoglycemia, Hypoketosis
Cause: MCAD deficiency, Carnitine deficiency, CPT-1 deficiency(liver isozyme), Jamaican vomiting sickness
Myopathies fatty acid oxidation disorders
Organs, Symptoms, Cause
Organs: Muscle cardiac & skeletal
Symptoms: Muscle cramps during exercise
Cause: Myopathic Carnitine deficiency, CPT-2 deficiency
RLE of Cholesterol Synthesis
HMG CoA Reductase
HMG CoA Reductase: Substrate/Products
Substrate: HMG CoA (6C) + 2NADPH
Products: Mevalonate (6C) + 2NADP+ + CoA
Inhibitors/Activators HMG Coa Reductase
Inhibitors:
Glucagon
Cholesterol
Statin Drugs: Zocor, Lipitor
Activators: Insulin
How does AMP Kinase regulate HMG CoA Reductase
• Sterol-Independent Regulation of HMG- CoA Reductase
• High intracellular concentrations of AMP stimulate AMP Kinase which phosphorylates HMG-CoA and inactivates it
• Dephosphorylation by a phosphoprotein phosphatase (activated by insulin) activates HMG –CoA
Upregulation of HMG CoA reductase?
- The amount of HMG CoA reductase enzyme is regulated by intracellular (cytosolic) concentrations of Cholesterol
- Low cholestrol stimulates the release of a
regulatory (SREBP) protein from the ER - Sterol regulatory element binding protein
(SREBP) binds to a region in the HMG CoA reductase gene called sterol responsive element (SRE) resulting in increased transcription of the HMG CoA reductase gene and subsequent increase in the amount of HMG CoA reductase.
When does proteolysis of cholesterol occur?
High Intracellular cholesterol and/or Mevalonate leads to rapid proteolysis of HMG CoA Reductase enzyme by the ubiquitin system in proteosomes.
SLOS (Smith-Lemli-Opitz Syndrome)
A genetic defect of cholesterol synthesis (autosomal recessive)
7-dehydroxycholesterol Reductase, needed for double bond formation in the ring B, is deficient.
Relatively common, leads to microencephaly and other embryological malformations, surviving children have an IQ 20-40
Synthesis of palmitate from Acetyl CoA requires how many ATP and NADHs
14 NADPHs & 7 ATPs
Sequence of synthesis of TAGs (Liver & Adipose tissue)
DHAP Glycerol phosphate Lysophosphatidic acid Phosphatidic acid(DAG phosphate) Diacylglycerol(DAG) Triacylglycerol (TAG)
Activation Facid(Cytosol): Enzyme/Substrate/Products
Enzyme: Fatty Acyl CoA synthetase
Substrate: Fatty acid + CoASH + 2ATP
Products: Fatty Acyl Coa + AMP + PPi