Week 2 Flashcards
A cholesterol derivative that is a component of bile salts.
What is Cholic acid?
Cholesterol is synthesized in four phases, all of which occur in the_________.
cytoplasm
the key regulatory enzyme in Cholesterol Biosynthesis:
HMG CoA Reductase
First the precursor of cholesterol is________ (6C), and synthesized by the condensation of 3 molecules of _______.
mevalonate
acetyl-CoA
Step 1: of Cholesterol Synthesis
Mevalonate (6C) Formation
tep 2: of Cholesterol Synthesis
Formation of an Isoprenoid (5C)
The cost of forming an Isoprenoid (5c)
Start with Mevalonate (6c)
3 ATP
1 Decarboxylation
6c Mevalonate
Step 3 of Cholesterol Synthesis
Condensation of Isoprene into Squalene (30c)
Step 4 of Cholesterol Synthesis
Cyclization of Squalene to Lanosterol and then 19 more steps, while losing three carbons to make cholesterol.
HMG-CoA is produced independently in mitochondria and in cytosol.__________ HMG-CoA is used to make ketone bodies._________ HMG-CoA is used to make cholesterol.
Mitochondrial
Cytosolic
The Enzyme that uses HMG-CoA to make ketone bodies
HMG-CoA lyase
The Enzyme that uses HMG-CoA to make Cholesterol
HMG-CoA reductase
Name the Bile salts derivatives of cholesterol
Glycocholate (glycine on C-17)
and
Taurocholate (tourine on C-17)
Classes of steroids from Cholesterol
Progestagens
Glucocorticoids
Mineralocorticoids
Androgens/Estrogens
An important intermediate molecule
pivotal between TAGs and phospholipids
phosphatidate
ω -6 and ω-3 series Eicosanoids
compete for same enzymes. What are they? (3)
cyclooxygenase
5-Lipoxygenase
Leukotrienes
Essential Glucogenic AA’s
Histidine
Methionine
Threonine
Valine
Glucogenic and Ketogenic Essential AA’s
Isoleucine
Phenylalanine
Tryptophan
Essential Ketogenic AA’s
Leucine
Lysine
Pepsinogen (Zymogen) activates
–> Pepsin
Protein leaving stomach stimulates_________ release in the duodenum, triggering the release of the main digestive enzymes by the pancreas.
cholecystokinin
Cholecystokinin (CCK) stimulates
- gall bladder bile release
- Release of pancreatic digestive enzymes
- Slows down gastric empting
__________(duodenum hormone) activates release of basic solution from pancreas
Secretin
Cuts Arginine and Lysine residues,
Trypsin
Cuts Aromatic amino acids
Chymotrypsin:
Cuts Hydrophobic amino acids
Elastase
Determinants of Protein Longevity
Oxidation
PEST sequences (Proline, Glutamate, Serine, Threonine)
Amino terminus sequence (N-terminal rule)
PEST sequences
Proline, Glutamate, Serine, Threonine
Other proteins are broken down by being tagged by a protein called_________ and degraded by the_____________.
ubiquitin
proteasome
Duodenum enzyme, converts pancreatic trypsinogen to trypsin.
Enteropeptidase
Transfer of amino groups (usually to α- ketoglutarate) is catalyzed by ___________
And these require the coenzyme ____________
aminotransferases
pyridoxal phosphate (vitamin B6)
Catalyzes transfer of the amino group of alanine to α-ketoglutarate to form pyruvate and glutamate.
Alanine aminotransferase (ALT)
Exception to the rule that aminotransferases funnel amino groups to form glutamate. Transfers amino groups from glutamate to oxaloacetate, forming aspartate.
Aspartate aminotransferase (AST)
________is the only amino acid that undergoes rapid oxidative deamination, a reaction that is catalyzed by ______________ ________.
Glutamate
glutamate dehydrogenase
_______________________ requires N- acetyl glutamate for activity, whose concentration increases after a protein rich meal
Carbamoyl phosphate synthetase I
____________links the Urea cycle with Gluconeogenesis and Transamination of Oxaloacetate
Fumarate
The enzyme_________ cleaves Arginine to Ornithine and Urea occurs almost exclusively in the______.
Arginase
liver
Cost of the urea cycle:
4 high energy phosphate bonds broken.
After glutamine reaches the liver:
Glutamine + H2O —-> Glutamate + NH4+
This reaction is catalyzed by the enzyme________
Glutaminase
Ammonia is also transported from muscle to liver in the form of_______
alanine
In muscle tissue Alanine is formed by the transamination of_________ to_______.
Once in the liver alanine reacts with _________ to reform “______” and “__________” (Alanine aminotransferase).
glutamate to pyruvate
α-ketoglutarate
pyruvate and glutamate
Acquired hyperammonemia: usually due to _____ _______.
liver cirrhosis
What is the general chemical composition and source of folic acid.
a. Pteridine
b. PABA (pSaminobenzoate)
c. Glutamate
Dietary Folic Acid Is catalyzed by ________ to tetrahydrofolate by Breaking double bonds to__ and replacing with __
(dihydrofolate reductase)
N replacing with H+
Lack of folic acid is the most common
vitamin deficiency in the world. Because blood
cells turn over rapidly, folate deficiencies usually
seen first as __________ _________.
megaloblastic anemia
Tetrahydrofolate is Required for…
Required for purine, thymine and
amino acid metabolism.
The most reduced group carried by Tetrahydrofolate.
-CH3 Methyl (N5)
The intermediate group carried by Tetrahydrofolate.
-CH2- Methylene (N5-N10 bridge)
The most oxidized group carried by Tetrahydrofolate.
- CHO Formyl (N5 or N10)
- CHNH Formimino (N5)
- CH= Methenyl (N5-N10 bridge)
S-Adenosylmethionine (SAM) is synthesized from Synthesized from___ ATP and__________. All the phosphate is removed
3 ATP Equivalents
methionine
_______________________ is the rate limiting step of the methyl cycle.
Methylene tetrahydrofolate reductase
Glutamine is formed from
glutamate by ________.
glutamine synthetase
Serine is the major biosynthetic precursor of both________ and________.
glycine
cysteine
The important antioxidant ________ is made from cysteine
Glutathione
Enough_______ is synthesized by the urea cycle to meet the needs of an adult but not those of a growing child.
arginine
Tyrosine can be produced from the essential amino acid phenylalanine in a single step catalyzed by _____________.
Reaction requires molecular oxygen and coenzyme______________
Phenylalanine hydroxylase
tetrahydrobiopterin
Which tissues does Heme synthesis mostly take place in?
In the liver and bone marrow.
Disease where porphryin intermediates build up and heme is not formed
Porferers (king George III had this)
3 allosteric (negative) effectors of Hemoglobin
- –BPG 2
- H+
- CO2
2,3 -BPG binds
converting__ state to___ state and
favoring oxygen ______.
R
T
Release
In the smoker, high ______ is still
present in the hemoglobin in the
lungs, remaining in the ___ state.
2,3-BPG
T
Fetal hemoglobin tetramers include two __chains and two _____Chains
α chains
γ chains
Besides pH in what way does CO2 decrease hemoglobin’s affinity for O2?
Carbon dioxide stabilizes deoxyhemoglobin by reacting with the terminal amino groups to form carbamate
Enzyme important for the production of bicarbonate
carbonic anhydrase With (Zn) cofactor
RBCs that are cycle type have decreased solubility from?
a valine residue for a glutamate residue in position 6 of β-globin. Decreases the solubility of deoxyhemoglobin,
Smokers also ingest a lot of___ which competes with oxygen for binding to heme group.
CO
What are the precursor molecules of purines?
Glycine
aspartic acid
glutamoine
CO2 and THF Coenzymes (Tetrahydrofolate)
What are the precursor molecules of pyrimidines.
Aspartic acid, glutamine, CO2
What is the basic structure of purines?
6 and 5 ring base
What is the basic structure of pyrimidines?
one 6 ring base
Metabolic precursors of De novo synthesis of nucleotides
amino acids, ribose 5-phosphate, CO2, and NH3
Synthesis of _____________ from PRPP is first committed step in purine nucleotide biosynthesis (de novo) What is the enzyme?
5- phosphoribosylamine
Enzyme: PRPP amidotransferase
where does De Novo Purine Nucleotide Biosynthesis occur?
Occurs primarily in liver but also in peripheral tissues.
Biosynthetic precursors of De Novo Purine Nucleotide Biosynthesis.
Atoms used from glycine, aspartate glutamine, CO2 and tetrahydrofolate.
Conversion of Nucleoside Monophosphates to Nucleoside Diphosphates is catalyzed by?
Adenylate kinase and guanylate kinase
Conversion of Nucleoside Diphosphates to Nucleoside Triphosphate is catalyzed by
Nucleoside diphosphate kinase
The “parent” molecule in both purine and pyrimidine biosynthesis…
a. Purine: Inosine monophosphate (IMP)
b. Pyrimidine: OMP
The Pyrimidine de Novo pathway is Catalyzed by _______________, an enzyme distinguishable from CPS I in its cytosolic location and its use of the amide group of glutamine for its nitrogen source.
carbamoyl phosphate synthetase II
De Novo Purine Nucleotide Biosynthesis
Rate limiting step and enzyme.
Synthesis of 5 phosphoribosylamine from PRPP
Conversion of Ribonucleotides to Deoxyribonucleotides
Requires the enzyme ___________________.
Requires_________ as a reducing agent. (protein with SH groups that get oxidized).
To continue, the latter must be regenerated. ___________catalyzes reduction of the disulfide using NADPH.
Ribonucleotide reductase (RNR)
thioredoxin
Thioredoxin reductase
Pyrimidine bases can be salvaged using enzyme ___________________ to form the respective nucleotides. However, this is not a significant route and very few pyrimidine bases are salvaged.
enzyme: pyrimidine phosphoribosyltransferase) using PRPP
Name the 2 enzymes involved in purine base salvage.
A. Adenine phosphoribosyl transferase (APRT)
i. Adenine + PRPP SS> AMP + PPi
B. Hypoxanthine V Guanine phosphoribosyl transferase (HGPRT)
i. (Note dual substrate specificity)
ii. Hypoxanthine + PRPP SS> IMP + PPi
iii. Guanine + PRPP SS> GMP + PPi
gout and the LeschSNyhan syndrome have an enzyme deficiency in common. What is the enzyme?
Hypoxanthine V Guanine phosphoribosyl transferase (HGPRT)
Gout is characterized by__________.
hyperuricemia Build up of uric acid
_________inhibits xanthine oxidase, resulting in an accumulation of hypoxanthine and xanthine compounds more soluble than uric acid.
Allopurinol
the biological basis of Severe Combined Immunodeficiency disease (SCID)
SCIDs Adenosine Deaminase (ADA) deficiency
Involves TScell and BScell dysfunctions
Usually die young
enzymes cannot make a fatty acid with a double bond more than ___ carbons from carboxyl end
enzymes cannot make a fatty acid with a double bond more than 9 carbons from carboxyl end
Omega 6 – forms Arachadonic acid – Eicosanoids for inflammation
Linoleic Acid
Omega 3 – forms Eicosanoids for ant inflammation
Linolenic Acid
This is a class of compounds that exert hormone-like effects in many physiological processes
eicosanoids, such as prostaglandins.
Enzyme only useful for short and medium chain fatty acids.
Gastric lipase (pH 7 optima)
Bile acids are cholesterol derivatives that are synthesized by the liver and secreted as…
glycine or taurine conjugates.
Most bile acids are reabsorbed in the small intestine, returned to the liver via the portal vein, and may be reSsecreted. Interrupting this cycle will lower cholesterol (medications, fiber, etc.)
Enterohypatic Cycle
Released from jejunum in response to chyme in duodenum
- Stimulates gall bladder bile release
- Release of pancreatic digestive enzymes
- Slows down gastric emptying
Cholecystokinin
i. Released in duodenum in response to the low pH of the chyme entering the intestine
ii. Induces pancreas to release a bicarbonate solution to neutralize the acidiic pH of the chyme
iii. Notably, the first “hormone” identified (1902)
Secretin
converts TAGs into 2Smonoacylglycerol and free fatty acids
Pancreatic lipase
Stabilizes pancreatic lipase at lipid water interface
Colipase
Stabilize pancreatic lipase and in its formation, turns into
esterostatin to act as a satiety signal.
Colipase
degrades cholesterol esters to free fatty acids and cholesterol.
Cholesterol (sterol)esterase
Removes the fatty acid
at C2 leaving a lysophospholipid.
The remaining fatty acid at C1 can be removed by_______________, leaving a glycerylphosphorylbase
Phospholipase A 2
lysophospholipase
Intracellular fatty acids are sequestered by being bound with ____________.
(Takes fat and keeps in one area so that it cannot be disruptive)
Fatty acid binding protein 2
AKA
ntestinal-type fatty acid-binding protein (I-FABP)
1-FABP/FABP-2
Chylomicrons receive Apo ___ and Apo ___ in circulation from _________.
Apo C-II
Apo E
HDL
Fatty acids trapped in cells by conversion to fatty acylSCoA thioesters catalyzed by ___________.
fatty acyl CoA synthetase
note: 2 ATP equivalents used
rate limiting step of cholesterol synthesis
HMG Co A reductase
CM triacylglycerol is distribution
80% adipose, heart, muscle 20% liver
Promotes lipoprotein lipase activity
Apo C-II
Reservoir for Apo C-II and Apo E for VLDLs
and chylomicrons
HDL provides Apolipoproteins
A-1, activates LCAT (Lecithin-Cholesterol Acyl Transferase) also known as PCAT (phosphatidyl choline acyl transferase)) which catalyzes synthesis of cholesteryl esters using fatty acids cleaved from the membrane lipid lecithin.
Other Function of HDLs
Breaks triacylglycerols into free fatty acids that will travel through the blood via albumin.
Hormone Sensitive Lipase (stimulated by Glucagon through Phosphorylation)
CPT1 is Inhibited by…
Malonyl CoA (substrate for fat synthesis)
committed step to fatty acid synthesis
The carboxylation of Acetyl-CoA(2C) by acetyl-CoA carboxylase to form Malonyl-CoA(3C)
Acetyl CoA Carboxylase is inhibited by
Glucagon will phosphorylate this enzyme and inactivate it
The synthesis of one palmitate molecule requires__ molecules of acetyl-CoA, __ATP and___ NADPH
8 acetyl-CoA
7 ATP
14 NADPH
