Term
| Eico Obj 1: Name the four major families of eicosanoids, and say why they are called eicosanoids. |
|
Definition
prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT)
(prostacyclins considered a family are a kind of prostaglandin)
eico- means 20 in greek, there are 20 carbons in eicosanoids |
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Term
| Eico Obj 3: What are the three FAs that are used to make eicosanoids and what are their omega notations? |
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Definition
Dihomogammalinolenic 20:3(ω-6) (DHGLA) makes PGE1
Arachidonic Acid 20:4(ω-6)
makes PGE2
Eicosapentaenoic acid 20:5(ω-3) (EPA) makes PGE3 |
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Term
| Eico Obj 2: What is the general role of eicosanoids? Give examples of cells that use them and their functions (9) |
|
Definition
General role - Local Hormones
Endothelial cells, Smooth Muscle Cells, Leukocytes, T-cells, lymphocytes
peristalsis, uterine contractions, leukocyte aggregation, T-cell proliferation, lymphocyte migration, arteriole and venous contraction/dilation |
|
|
Term
|
Definition
paracrine – local message, two different cells
vs
autocrine – messages that are from and to the same kind of cell (platelet to platelet) |
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Term
Eico Obj 3: What does the enzyme phospholipase A2 (PLA2) catalyze?
How do glucocorticoids affect PLA2? How does Ca++ affect PLA2? |
|
Definition
catalyzes hydroylsis of a phospholipid at the ester bond of a phospholipid molecule FA at position two so they can be used for eicosanoid synthesis
Glucocorticoids inhibit
Ca++ activates |
|
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Term
| Draw a schematic for a membrane phospholipid |
|
Definition
G - FA
l
y
c - FA
e
r
o
l-P- Alcohol (such as choline) |
|
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Term
| Eico Obj 4: Describe the sources of the eicosanoid precursors that appear in your body’s membrane phospholipids |
|
Definition
You can get arachidonic acid from your diet, from animal fat. Or you could produce arachidonic acid from linoleic acid.
Alpha Linoleic Acid (ALA) is found in flax oil, and Eicosapentaenoic Acid EPA in fish oil. |
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Term
| Eico Obj 5: Name the pathway for the production of any of the thromboxanes or prostaglandins |
|
Definition
cyclo-oxygenase pathway
The name comes from the first enzyme in the pathway: cylco-oxygenase
Aspirin and other anti-inflammatory drugs inhibits the cyclooxygenase pathway, inhibiting platelet activity |
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Term
| Eico Obj 6: Write out the cyclo-oxygenase pathway and it's potential products (7) |
|
Definition
Cyclo-oxygenase with cofactor heme uses 2 O2 molecules to make PGGx(1,2 or 3 indicating the number of double bonds and where it came from since 2 double bonds are lost in the process of making PGGx)
Peroxidase then, using 2 Glutathione (GSH) moleucles as the reducing agents and combines them to a single GSSG (This is the oxidation of a thiol to a disulfide), and forms PGHx which then becomes either:
Thromboxane TXAx via TXA synthase
Prostaglandin PGIx via PGI synthase
Prostaglandin PGEx via PGE synthase --> which can become PGFx alpha via PGE 9-keto reductase
Prostaglandin PGDx via PGD synthase |
|
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Term
| What is the constitution of glutathione? (3) |
|
Definition
Three AAs binded to eachother in a tripeptide
Glutamate-cysteine-glycine |
|
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Term
| Eico Obj 7: Explain the effect of consuming fish oils on bleeding time. Explain the effect of aspirin on bleeding time. |
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Definition
fish oils increase bleeding time by decreasing platelet activity (aggregation)
TXA3 is less pro-aggregatory than TXA2
PGI3 is more anti-aggregatory than PGI2
asirin and other anti-inflammatory drugs increase bleeding time by decreasing platelet activity (aggregation) by irreversibly inhibiting cyclo-oxygenase via acetyl group donation
Endothelial cells can remake cyclo-oxygenase quickly because they have a nucleus, but platelets must be remade by megakaryocytes. |
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Term
| Eico Obj 8: Distinguish between COX-1 and COX-2 |
|
Definition
Cyclo-oxygenase 1 (COX-1) is responsible for making eicosanoids needed for everyday operations; hormones for peristalsis
cyclo-oxygenase 2 (COX-2) (inducible enzyme) is made by cells in the inflammatory system |
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Term
| Eico Obj 10: Describe the the 5-lipoxygenase pathway leading to leukotrienes |
|
Definition
Arachidonic acid gains a carboxyl group on C# 5 which is spontaneously reduced to an alcohol making it 5-HPETE
O2 is the oxidizing agent
leukotrienes don’t change the number of double bonds, so LTAx (Leukotriene A) can be 3,4, or 5
Before 5-HPETE breaks down to 5-HETE it is made to
LTAx which can go to
LTBx - an OH on the C5 instead of an O between the 5 & 6 C’s and an OH on the C12
Or go to
LTCx - all of glutathione attached at the C6 and OH on the C5
then
LTDx - Cys and Gly of glutathione (glutamate removed)
then
LTEx - only Cys of glutathione |
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Term
| What are the three lipoxygenases? |
|
Definition
5
12
15
Each is responsible for attaching a carboxyl group, making it a x-HPETE (x being the enzyme number), followed by spontaneous reduction to an alcohol where it is then called x-HETE |
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Term
| Eico Obj 12: Describe the mechanisms by which eicosanoids deliver their messages to target cells and the effects they have (5) |
|
Definition
Eicosanoid receptors are on the surface (meaning hydrophilic)
G-protein coupled (uses signal transduction with G-protein)
Some g-proteins inhibit adenylate cyclase
2 types of G-proteins stimulatory and inhibitory (of adenylate cyclase)
some activate phospholipase |
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Term
| Eico Obj 13: Give examples of glucocorticoids and describe mechanisms by which glucocorticoids are anti-inflammatory (7) |
|
Definition
cortisol = (same thing as) hydrocortisone
synthetic glucocorticoids
prednisone
dexamethasone
they inhibit recruitment of monocytes, macrophages, leukocytes by inhibition of production and release of inflammatory eicosanoids, reducing chemotaxis
suppress transcription and translation of COX-2
induce synthesis of family of proteins “lipocortins” by binding to glucocorticoid receptors & change gene expression
lipocortins inhibit phospholipase A2, stopping ability to make eicosanoids |
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Term
| Why glucocorticoids are important to an individual with Cushing's syndrome |
|
Definition
| If a person’s body makes too much cortisol they might not be able to mount the inflammatory or immune response they need, i.e. Cushing’s disease/syndrome. This person might have trouble fighting infections because the glucocorticoids are anti-inflammatory and at times you need the inflammatory response to fight infection |
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Term
| AA structures Obj 1: Describe some of the functions of your body’s proteins (8) |
|
Definition
Cell adhesion molecules are proteins
Some hormones are proteins such as insulin and glucagon
Ion channels and pumps in membranes
Almost all enzymes are proteins
Essential for movement (motor proteins) such as myosin
Elastin, keratin, and collagens are important proteins in connective tissues
Extra and intra cellular receptors
Antibodies |
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Term
AA Obj 2: Define AA residue
Why is glycine special? |
|
Definition
AA residue is used when amino acids are part of something bigger than themselves that’s at least a dipeptide in size
All amino acids are L (as opposed to D) except glycine since it has a symmetric center |
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Term
| Draw the structure of a D AA and an L AA |
|
Definition
L
.....COO-
+H3N-C-H
.....R
vs
D
..COO-
H-C-NH3+
..R |
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Term
| How does Littleton define pKa and pH? |
|
Definition
The higher the pKa the more a group wants to keep its proton on
The higher the pH, the greater the tendency to steal a H+ from an ionizable group |
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Term
| Which AA's don't have a three letter abbreviation that is the first three letters of its name? (4) |
|
Definition
Isoleucine - ile
Tryptophan - trp
Asparagine - asn
Glutamine - gln |
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Term
| What are the two smallest AAs? |
|
Definition
|
|
Term
| What are the three branched chain AAs? |
|
Definition
| Valine, Leucine, Isoleucine |
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Term
| What are the three aromatic AAs? |
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Definition
| Phenylalanine, Tyrosine, Tryptophan |
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Term
| What AAs have a hydroxyl group in their side chains? |
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Definition
| Serine, Threonine, Tyrosine |
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Term
| What are the two AAs that are a positively charged at physiologic pH? |
|
Definition
Arginine, Lysine
(Histidine part of the time in certain tissues, but not at physiologic pH) |
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Term
| What are the two AAs that are a negatively charged at physiologic pH? |
|
Definition
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|
Term
| What are the AAs that have a hydrolyzable amide group in the side chain? |
|
Definition
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Term
| What makes arginine unique? |
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Definition
| It has three Nitrogens in its side chain |
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Term
Draw phenylalanine's side chain
&
Draw tyrosine's side chain |
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Definition
CH2 on top of
Benzene Ring
CH2 on top of
Ortho-Phenol |
|
|
Term
|
Definition
|
|
Term
Draw cysteine's side chain
Draw methionine's side chain |
|
Definition
|
|
Term
|
Definition
|
|
Term
Draw aspartate and asparagine's side chains
Draw glutamate and glutamine's side chains (GLUTAMINE LIKELY TO BE ON TEST) |
|
Definition
Aspartate
CH2
COO-
Asparagine
CH2
C=O
NH2
Glutamate
CH2
CH2
COO-
Glutamine
CH2
CH2
C=O
NH2 |
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Term
| Be able to recognize Tryptophan, Threonine (draw), Arginine, Histidine, Proline |
|
Definition
Typtophan has the only double ring
Arginine is the longest with a CCCNCN chain
Threonine is best simply drawn to be remembered
HCOH
CH3
Histidine has a 5 membered ring attached via a methyl group
vs
Proline which has a 5 membered ring as part of it's general structure |
|
|
Term
What is the typical carboxyl group pKa range?
What is the typical amine group pKA? For a double bond? |
|
Definition
COO- is typically 2 to 4
NH3+ is typically 9 to 10
&
C=NH2+ is ~ 12 |
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|
Term
What is the pKa of histidine's R group?
What is the pKa of cysteine's R group?
What is the pKa of tyrosine's R group? |
|
Definition
pKa of histidine R group is 6 (The NH in its ring will grab a H+ with a pH lower than this becoming positive)
Cysteine pKa is 8.4 (will lose its H becoming negative)
Tyrosine's R group pKa is 10.5 (above this it will lose it's H+ becoming negative) |
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|
Term
What is the pKa of Lysine's R group?
What is the pKa of Arginine's R group? |
|
Definition
10.5
12.5
they will both lose their positive charges if pH exceeds pKa |
|
|
Term
What is the pKa of Aspartate?
What is the pKa of Glutamate? |
|
Definition
3.9
4.1
both of these will lose their H+ at pH values above the pKa values becoming neutral |
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|
Term
| Draw structures to illustrate an electrostatic bond between the side chains of a lysine residue and an aspartate residue at physiologic pH |
|
Definition
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|
Term
Urea Obj 1: Proteolytic Enzymes (5)
their precursors
and activators |
|
Definition
Pepsin, Trypsin, chymotrypsin, elastase, and carboxypeptidases
Pepsinogen, Trypsinogen, Chymotripinogen, Proelastase, Procarboxypeptidases
Pepsinogen self activated by H+
trypsin - enteropeptidase
chymotripsin - trypsin
elastase - trypsin
procarboxy – trypsin |
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|
Term
| How are AAs transported into the Hepatic Portal Vein? |
|
Definition
Via Na+-dependent carriers into the cell
Then the AA is goes into the vein via a Facilitated Transporter |
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Term
| Define Protelytic activation |
|
Definition
| The activation of an enzyme by peptide cleavage |
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Term
|
Definition
| pre-enzyme aka proenzyme or inactive form of an enzyme |
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Term
| Endopeptidase define and what cells produce these? |
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Definition
| Any of a group of enzymes, such as trypsin, chymotrypsin, pepsin, and elastase, which catalyze the splitting of polypeptide chains at nonterminal locations |
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Term
| What happens to blood levels of insulin, glucagon, nitrogen, and glucose after a high protein meal? |
|
Definition
Nitrogen goes up for four hours
glucose stays steady
insulin rises and falls after an hour
glucagon rises and falls after two hours |
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Term
| In what order are AAs listed? |
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Definition
| From N terminus to C terminus |
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Term
| Which cells are responsible for the protein breakdown in the small intestine and what do they secrete? (9) |
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Definition
| Pancreatic acinar cells secrete, Chymotrypsinogens, chymotripsin, Trypsinogens, trypsin, and Procarboxypeptidases A and B, carboxypeptidases, elastase |
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|
Term
| Which cells secrete pepsinogen? |
|
Definition
|
|
Term
| Describe the fates of amino acids in the fed state (6) |
|
Definition
The TCA cycle
Proteins for the liver and other tissues
Made into TAG's which are put into VLDL
Made into glucose to go to the blood
Made into glucose to become glycogen
made into essential nitrogen containing compounds |
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Term
| Urea Obj 2: Describe the ultimate fate of most of the amino acid nitrogen in the body. Draw the chemical structure of urea. |
|
Definition
goes into urea; excreted in urine
....O
H2N-C-NH2 |
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Term
Urea Obj 3: Spell the name of the cofactor that is required in the active site of all transaminases.
What enzyme is this same cofactor needed for? |
|
Definition
pyridoxal phosphate (PLP)
Glycogen Phosphyorylase also needs PLP |
|
|
Term
| What two rnxs are needed to make PLP from B-6? |
|
Definition
oxidization of primary alcohol to aldehyde NAD+
and
add a phosphate group |
|
|
Term
Give the reaction (both reactants and both products) of alanine transaminase (ALT) and aspartate transaminase (AST)
Draw all molecules involved |
|
Definition
Pyruvate <--ALT--> Alanine
Glutamate <--ALT--> a-Ketoglutarate
OAA <--AST--> Aspartate
Glutamate <--AST--> a-Ketoglutarate |
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Term
| Urea Obj 6: Describe the function of PLP in transamination rnxs (4) |
|
Definition
It forms a double bond with the Nitrogen of the amine group being transferred.
The newly formed a-keto acid is then released, and PLP becomes Pyridoxamine phosphate.
Pyridoxamine phosphate then forms a C=N double bond with the a-keto acid it's going to donate the amine group to.
It then releases the newly formed amino acid. |
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Term
| Urea Obj 7: Describe the reaction catalyzed by glutamate dehydrogenase. |
|
Definition
uses either NAD+ or NADP+
transfers ammonium ion from glutamate or vice verse |
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Term
| Urea Obj 7: What makes the five-carbon carbon skeleton shared by α-ketoglutarate and glutamate so important? |
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Definition
| Glutamate collects nitrogen from other amino acids and either releases it as NH4+ or turns OAA to aspartate via transamination. Both of which go into the urea cycle as anaplerotic intermediates. |
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Term
| What are the 5 rxns of the urea cycle? What two places does it occur? |
|
Definition
In mitochondria
HCO3- + NH4+ + 2 ATP --Carbamoyl phosphate synthetase I (CPSI)--> Carbamoyl phosphate + 2 ADP + Pi
Ornithine + Carbamoyl phosphate --Ornithine transcarbamoylase--> Citrulline
In cytosol
Citrulline + Aspartate + ATP --Argininosuccinate synthetase--> Argininosuccinate + AMP + PPi
Argininosuccinate --Argininosuccinate lyase--> Fumarate + Arginine
Arginine + H2O --Arginase-->
Ornithine + Donation of amine group to urea molecule |
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|
Term
| Urea Obj 8: Name the two major carriers of nitrogen in the blood and explain why ammonium is not a good carrier of Nitrogen in the blood. |
|
Definition
Alanine and Glutamine
Ammonium is toxic to neural cells |
|
|
Term
| Describe the glucose alanine cycle (5) |
|
Definition
Glucose --glycolysis--> pyruvate
pyruvate + Glutamate <--ALT--> alanine + a-KG (which gets converted back into glutamate by random AAs in muscle)
Alanine (carbons of alanine) --Gluconeogenesis--> Glucose + Nitrogen
Glucose goes back to muscles
Nitrogen to urea cycle (in liver) --> urea --> urine (in kidney) |
|
|
Term
| Describe a-KG as a Nitrogen transporter out of muscle and peripheral tissues to the liver for the urea cycle (4 rnxs) |
|
Definition
a-KG + NH4+ + NADPH <--GDH--> Glutamate + NADP+
Glutamate + NH4+ + ATP --Glutamine synthetase--> Glutamine + ADP + Pi
Glutamine to liver
Glutamine --Glutaminase--> Glutamate + NH4+
Glutamate <--GDH--> a-KG + NH4+ |
|
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Term
| What can happen neurologically as a result of liver disease (e.g. hepatitis)? |
|
Definition
| The urea cycle doesn’t work so well and in that case ammonium ions rise in the body, causing neural cell death. |
|
|
Term
| Draw the chemical structure of carbamoyl phosphate |
|
Definition
|
|
Term
| Describe the two sides of the Krebs bi-cycle (7) |
|
Definition
Argininosuccinate splits into Fumarate and Arginine
fumarate --fumarase→ malate
Malate + NAD+ --MDH→ NADH + OAA
OAA + Glutamate ←→ a-Ketoglutarate + Aspartate
--
Arginine --Arginase--> Ornithine + NH2 to Urea
Ornithine + Carbamoyl Phosphate --ornithine transcarbamoylase--> Citrulline + Pi
--
Aspartate and Citrulline can then combine to form Argininosuccinate |
|
|
Term
| Give a sequence of reactions by which the fumarate produced by the urea cycle can enter the gluconeogenic process (4) |
|
Definition
Argininosuccinate --Arginino succinate lyase--> Arginine + Fumarate
Fumarate --Fumarase--> Malate
Malate + NAD+ --MDH--> OAA + NADH
OAA + GTP --PEPCK--> GDP + PEP |
|
|
Term
| List the main Nitrogenous excretory waste products of the body (5) |
|
Definition
Urea
NH4+ (ammonium ion) - produced mainly in the kidneys instead of traveling through the blood from some other organ (because that would be dangerous to nerve cells) to be safely excreted from the body.
Creatinine (waste product) - from the spontaneous non-enzymatic breakdown of creatine
Uric acid (urate): The conversion of purine nucleotides to uric acid occurs in the liver and then the uric acid to the kidneys & is excreted in urine
Heme (has 4 Ns surrounding an Fe) breaks down into bilirubin (largely done in spleen by Macrophages called reticuloendothelial cells typically from RBCs) which is carried in the blood by albumin to the liver where it is conjugated by UDP-Glucaronate which donates to glucaronates to conjugate it |
|
|
Term
| Enzyme responsible for creatine activity |
|
Definition
| creatine ←Creatine Kinase (CPK or CK)→ creatine phosphate |
|
|
Term
| What is the body's way of combating acidosis? |
|
Definition
| In the kidneys suck up glutamine when the body is in acidosis. The glutamine is then used to put ammonium ion in the urine, where you’re not only getting rid of ammonia (nitrogen) but also a proton. |
|
|
Term
| What three compounds are needed for the synthesis of creatine? |
|
Definition
| Methionine in the form of S-adenysyl methionine (SAM), Arginine, and glycine |
|
|
Term
| Draw a purine ring system |
|
Definition
-
Hexose ring with 2 Ns in othro alignment away from pentose ring with N (on top) and NH (on bottom) in an ortho alignment |
|
|
Term
| How is UDP-glucaronate formed? |
|
Definition
| From UDP-glucose via oxidization at glucose position 6 so that C6 goes from primary oxygen to carboxylic acid |
|
|
Term
| Draw Isoleucine's side chain |
|
Definition
|
|
Term
| Draww valine and leucine's side chains |
|
Definition
|
|
Term
| Which cells secrete stomach acid? |
|
Definition
|
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