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
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)
Coenzyme of Propionyl CoA Carboxylase?
Biotin
Coenzyme for Methylmalonyl Coa mutase?
Vit B12
Enzyme to form & store cholesteryl esters?
ACAT
Enzymes cleaves TAGs in Chylomicrons & VLDL
Lipoprotein lipase
Proteins that anchor and activate Lipoprotein Lipase
Anchor: Heparan sulfates
Activates: Apo C2
Stimulates & Inhibits the reaction: LDL—> OxLDL
Stimulators:Superoxide, NO, Hydrogen peroxide, Other oxidants
Inhibitors: Vit E, Ascorbic acid, B-carotene, other antioxidants.
Role CETP (cholesteryl ester transfer protein)
Allows transfer the transfer of TAGs from VLDL into HDL in exchange for cholesteryl esters
What’s so special with HDL
- Potential anti-atherogenic properties
- Reverse cholesterol transport using as key players apo A-1, LCAT, plasma membrane ABC-transporter for free cholesterol and CETP
- Contains enzymes that reduce LDL oxidation (Paraoxonase and PAF acetylhydrolase)
- Potential plaque stabilization properties
- HDL-mediated cholesterol efflux reduces
plaque lipid content - HDL may reduce plaque macrophage
content and their activity and increase plaque smooth muscle content and prevent rupture
- HDL-mediated cholesterol efflux reduces
Malicious Enzyme: Substrates, Products
Substrate: Malate, NADP+
Products: Pyruvate, NADPH + H+
Thioesterase: Substrates, Products
Substrates: Palmitoyl-ACP + H2O
Products: Palmitate + ACP-SH
Required to produce TAG from 2-Monocylglycerol
2 Acyl CoA:monoacylglycerol acyltransferase
& 2 Fatty Acyl-CoA
Cholesterol —> Cholic Acid
Enzyme?
Inhibitor/Activator?
Cholesterol 7-alpha-hydroxylase (catalyze a the addition of OH group to C-7)
Activator: Cholesterol
Inhibitor: Cholic Acid
Coenzyme for Lead
Zinc
Ribose 5-P—-> 5-Phosphoribosyl 1 Pyrophosphate (PRPP)
Enzyme, Cofactor, activator/inhibitor
PRPP Synthetase
Cofactors: ATP—> AMP & Mg2+
Activator: Pi
Inhibitor: Purine nucleotides
Committed step of nucleotide synthesis: Enz, Substrate, Products, Cofactors, Activators, Inhibitors
Enz: Glutamine Phosphoribosyl Pyrophosphate Amidotransferase
Substrate: 5 Phosphoribosyl 1 Pyrophosphate + Glutamine
Products: 5 Phosphoribosylamine + Glutamate
Cofactors: Mg2+
Activator: PRPP
Inhibitors: AMP, GMP, IMP
Pteridine Precursor + Aminobenzoic Acid (PABA) —-> Folic Acid
Enzyme, Cofactor, Drug that inhibits
EnzyMe: Dihydropteroate Synthetase
Co-factor: ATP, Glutamate
Drug: Sulfonamide
Dihydrofolate reductase
Substrate/Product, Cofactor, Inhibitor
Substrate: Folic Acid
Product: THF acid
Co-factor: 2NADPH
Inhibitor: Methotrexate
Serine hydroxymethyltransferase
Substrate, Product, Cofactor
Substrate: Serine
Product: Glycine
Co-factor: THF—> N5,N10 Methylenetretrahydrofolate
Enzymes that transport bilirubin in liver
- Ligand protein
- Z protein
Synthesis of CTP from UTP
Substrate, Products, enzymes, cofactors
Substrate: UTP
Product: CTP
Enzyme: CTP synthase
Cofactor: Glutamine + ATP
Ribonucleotide—-> Deoxyribonucleotides
Enzyme, activator, inhibitor
Enz: Ribonucleotide di phosphate Reductase
Activator: ATP
Inhibitors: dATP, hydroxyurea
Enzyme salvages pyrimidines
Pyrimidine Phosphoribosylthransferase
PRPP is the source of ribose phosphate
Which Prostaglandins are Mediators of Inflammation
PGE2
PGF2a
Precursor for Arachidonic acid
Linolenic acid
Eicosapentanoic acid #
20:5 w3
PG and TX from Omega3
Reaction catalyzed by Adenosine Deaminase
Adenosine—-> Inosine
Release NH3
Reactions catalyzed by Purine nucleoside Phosphorylase
Inosine—-> Hypoxanthine
Guanosine—-> Guanine
What stimulates Tissue factor pathway inhibitor TFPI
& what is its function?
- Heparin
- Bind and inhibit Factor Xa & Factor VIIa/tissue factor
Which is administered first: Warfarin or heparin
Heparin because warfarin is slow acting.
What enzyme oxidized cystein to taurine
Cysteine di oxygenate
How much ATP required in Purine synthesis?
4 ATP
Cholesterol modified by bacteria in intestine to form:
Coprostanol & Cholestanol
What increases in Acute Hepatitis and long standing hepatitis?
Acute: ALT level»>AST levels
Long standing alcohol cirrhosis: AST»>ALT (AST:ALT ratio approx 2:1)