Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
89 Cards in this Set
- Front
- Back
Oxidation # of carbons in one glucose:
|
0
|
|
Oxidation # of carbons for 2 Pyruvate:
|
+4 (+2/2pyruvate)
|
|
Number of NAD+ reduced in pyruvate oxidation?
|
2 (1 molecule / pyruvate)
|
|
Oxidation # of carbons for 6 CO2:
|
+24 (+4/6CO2)
|
|
Number of NAD+/FAD reduced in CO2 oxidation?
|
10 NAD + 2 FAD = 12
(2 electrons per NAD or FAD) |
|
Sequence of oxidation from CH4 to CO2:
|
CH4 -> CH3-OH / CH3NH2/ H2C=CH2
-> CH2=O -> HCOOH -> CO2 |
|
# electrons released in each oxidation:
|
2
|
|
Always present at an oxidation:
|
NAD+ or FADH+
|
|
Enzyme that converts pyruvate to alanine:
-Coenzyme -Cellular site -Rev/irrev |
Alanine aminotransferase (ALT)
Coenzyme = PLP Site = Cytosol Reversible |
|
Enzyme that converts pyruvate to lactate:
-Cellular site -Rev/irrev |
Lactate Dehydrogenase (LD)
Cell site: Cytosol Reversible |
|
Enzyme that converts Pyruvate to Oxaloacetate:
-Coenzyme -Cellular site -Rev/irrev |
Pyruvate Carboxylase
-Biotin -Mito matrix in liver/kidney -Irreversible |
|
Enzyme that converts Pyruvate to AcCoA:
-Coenzyme -Cellular site -Rev/irrev |
Pyruvate dehydrogenase complex
-TPP, Lipoic acid, FAD -Mito matrix -Irreversible |
|
Enzyme that converts Pyruvate to Acetaldehyde -> Alcohol:
-Coenzyme -Cellular site -Rev/irrev |
Pyruvate decarboxylase
-TPP -Microbes only NOT MAMMALS -Irreversible |
|
Why is Pyruvate so important?
|
It sits at a critical branchpoint with 4 possible fates:
|
|
What are the 4 fates of pyruvate? (things it can be converted to)
|
1. Alanine
2. Lactate 3. AcCoA 4. Oxaloacetate |
|
Where is the energy in pyruvate?
|
-Its ability to be further oxidized
-The 2 NADH produced in glycolysis (G3P dehydrogenase) |
|
What important factor determines the fate of pyruvate?
|
Whether oxygen is available or not.
|
|
What is the oxidation number of each molecule in going from methane to CO2 via methanol, formaldehyde, formic acid, CO2?
|
1. Methane = -4
2. Methanol = -2 3. Formaldehyde = 0 4. Formic acid = +2 5. Carbon Dioxide = +4 |
|
Back to the fates of pyruvate:
|
ok
|
|
Why/when does pyruvate get converted to Lactate and Alanine?
|
When skeletal muscles don't get enough O2 like during intense exercise.
|
|
What 2 things need to happen during intense exercise?
|
1. Replenish NAD+
2. Resynthesize glucose (liver) |
|
What is the body's simplest solution for achieving these goals?
|
1. Break down pyruvate to lactate
2. Send lactate to liver to make glucose |
|
Why occurs in the similar process that converts pyruvate to L-alanine instead of lactate?
|
1. L-glutamate donates NH3 to pyruvate - makes L-alanine
2. NADH -> NAD+ at the same time; replenishes it for tissue. |
|
How is L-Alanine useful?
|
Sent to the liver, it supports gluconeogenesis.
|
|
What is required for pyruvate to participate in gluconeogenesis in the liver?
|
Conversion to PEP via 2-step process
|
|
What is the first step in going from Pyruvate -> PEP?
|
Conversion to Oxaloacetate
|
|
What happens to pyruvate when oxygen is PLENTIFUL?
|
Gets oxidized to AcCoA
|
|
Why is AcCoA a very important irreversible step in biology?
|
BECAUSE IT CANNOT BE CONVERTED BACK TO GLUCOSE.
|
|
How does the body prevent overproduction of AcCoA from glucose (depleting glucose)?
|
By tightly regulating the enzyme for the reaction - PDH complex.
|
|
What reaction with Pyruvate occurs in microbes but not mammals?
|
Pyruvate->Acetaldehyde/Ethanol
|
|
Where in the body does gluconeogenesis predominantly occur?
|
90% in liver
10% in kidney |
|
What are the general characteristics of Pyruvate? (3 things)
|
1. Strong acid (pKa 2.5)
2. Simplest a-keto acid 3. Low concentration - always gets converted to something. |
|
What really is the purpose of ALT?
|
To convert pyruvate to a product that is suitable for transport to the liver.
|
|
And the good byproduct of this conversion is:
|
Regeneration of NAD+ for the cell
|
|
What additional enzyme is necessary for the proper action of ALT?
|
Glutamate dehydrogenase (GDH)
|
|
3 good things accomplished by the ALT reaction:
|
1. NADH is oxidized to NAD+ and glycolysis can continue
2. L-alanine (pyruvate equiv) can make glucose in liver. 3. NH3 is converted to derivative for safe transport to liver; prevents toxicity. |
|
How does LDH accomplish conversion of pyruvate to lactate?
|
By using NADH to donate a proton to C2 of pyruvate
|
|
What about LDH makes it a good enzyme for this conversion?
|
Its reactive site contains
-Arg to hold on to COO- -His to donate proton to carbonyl oxygen -> -OH |
|
How does NADH donate its H- to pyruvate?
|
The H- ion attacks C2 and bumps electrons up to grab on to histidine's proton.
|
|
What is important about NADH's participation in the LDH rxn?
|
Sterespecific - H donation comes from only one side of the NADH ring.
|
|
where is PDH complex located?
(pyruvate dehydrogenase) |
In the mitochondrial matrix
|
|
What is PDH composed of?
(3 components) |
ACTUALLY THREE ENZYMES:
E1. Pyruvate dehydrogenase E2. Dihydrolipoyl transacetylase E3. Dihydrolipoyl dehydrogenase |
|
What 3 cofactors does PDH use?
|
1. TPP (thiamine pyrophosphate)
2. Riboflavin 3. FAD |
|
What happens to Pyruvate in step 1 of PDH?
-Enzyme component -Cofactor |
Enzyme = PDH
Cofactor = TPP Pyruvate -> Hydroxyethyl TPP + CO2 (lost) |
|
What happens to Hydroxyethyl TPP in step 2 of PDH?
-Enzyme component |
Enzyme2 = Dihydrolipoyl transacetylase
-Hydroxyethyl TPP has neg charged carbon; attacks S of lipoamide -Produces Acetyl-dihydrolipoamide |
|
What happens in step three of PDH? What enzyme?
|
Still at Enzyme 2; CoA is incorporated into intermediate to produce Acetyl CoA.
|
|
How is the reduced lipoamide generated by Acetyl CoA production OXIDIZED to regenerate it?
|
By E3, dihydrolipoyl dehydrogenase
|
|
What cofactor and substrate is used by E3?
|
-FAD cofactor
-NAD+ substrate |
|
Since NADH is produced in AcCoA production, this is obviously not something you want to be doing in strenuously exercising muscle.
|
Agreeed.
|
|
What is special about lipoamide?
|
It has a long swinging arm that acts as a Lysine Tether to transport Acetyl group to active site for CoA addition
|
|
What type of reaction is catalyzed by PDH complex?
|
Oxidative decarboxylation
|
|
Is dihydrolipoamide good or bad?
|
Good if it can be regenerated, but you don't want to stay there. E3 better regenerate lipoamide if you want to keep producing AcCoA
|
|
What key role does PDH play in glucose metabolism?
|
Couples Glycolysis and TCA
|
|
3 goals accomplished by PDH:
|
1. Pyruvate -> AcCoA
2. Energy of oxidative decarboxylation is CAPTURED 3. Complex is regulated |
|
In what 2 forms is the energy of the PDH complex captured?
|
1. NADH -> for further use
2. Hi energy thioester bond of AcCoA |
|
Which components of PDH are reversible/irreversible reactions?
|
E1 = irreversible
(overall rxn is irreversible) E2 and E3 = reversible |
|
In what 2 ways is PDH regulated?
|
1. Feedback inhibition by NADH and AcCoA
2. Interconversion between active/nonactive forms |
|
What form of PDH is
-Active -Nonactive What makes these forms? |
Active = DEphosphorylated
Nonactive = phosphorylated PDH phosphatase/PDH kinase |
|
Which enzyme turns on PDH?
Which enzyme turns it off? |
PDH Phosphatase turns PDH on
PDH Kinase turns PDH off |
|
What will make PDH Kinase act on PDH?
|
High Energy State metabolites:
-AcCoA -NADH -ATP Don't need Kreb's cycle |
|
What will make PDH Phosphatase turn PDH on?
|
Low Energy State molecules:
-Mg2+ -Ca2+ -Insulin in adipose |
|
Why does Insulin turn on PDH via PDH phosphatase?
|
B/c it signals high blood glucose; adipocytes need AcCoA to make fat.
|
|
What is the message Insulin gives adipose tissue in fed state?
|
-Turns on PDH phosphatase
-Turns on PDH -Pyruvate -> AcCoA -AcCoA -> FA biosynthesis |
|
TPP is derived from:
|
Thiamine - vitamin B1
|
|
Deficiency of Thiamine leads to:
|
Beriberi
|
|
What is beriberi? who gets it?
|
Disorder w/ neurologic/CV symp.
-Far East people who eat rice -ALCOHOLICS |
|
What term describes the condition of drinking ethanol rather than thiamine-containing foods?
|
Alcoholic Polyneuropathy
|
|
What does Thiamine deficiency in alcoholics irreversibly lead to?
|
Wernicke-Korsakoff Syndrome
|
|
What do all enzymes that require TPP (thiamine pyrophosphate) do?
|
Transfer activated aldehyde units
|
|
What are the 4 known Thiamine requiring mammalian enzymes?
|
-Transketolase (PPP)
-PDH (pyruvate mtbsm) -a-Ketoglutarate Dehydrog (TCA) -Branched chain of above (AA) |
|
What is the substrate for all of these enzymes? In the last 3?
|
All use a ketone substrate
Last three involve a-ketoacid substrates. |
|
How is Beriberi diagnosed?
|
RBC Transketolase assay
|
|
What is deficiency of E3?
|
Leigh's disease - less than 10 cases known
|
|
Rxn catalyzed by Pyruvate carboxylase?
-Coenzyme -Substrate |
Pyruvate -> Oxaloacetate
Coenzyme = Biotin Substrate = ATP |
|
What is the key feature of all Biotin-dependent enzymes?
|
Reaction occurs in 2 steps - first step attaches CO2 to biotin via ATP -> ADP + Pi
|
|
2 steps in Pyruvate carboxylase reaction:
|
1. HCO3 attached to Biotin via ATP cleavage
2. CarboxyBiotin + Pyruvate -> Oxaloacetat + Biotin |
|
ONlY 2 OTHER BIOTIN-DEPENDENT ENZYMES IN MAMMALIAN BIOCHEM:
|
-Propionyl-CoA Carboxylase
-AcetylCoA Carboxylase (both involved in FA metblsm) |
|
What is the coenzyme used by Pyruvate Decarboxylase? What is this reaction specific to?
|
TPP - only in MICROBES
|
|
What is the Pyruvate decarboxylase reaction?
|
Just like PDH but no NAD used; NOT A REDOX
|
|
What does microbe Pyruvate decarboxylase produce?
|
Ethanol - in microbes in the human gut too.
|
|
When the bloodstream is cleared of glucose, but you're not fasting, what does the liver do?
|
Sends glucose to muscles (by breaking down glycogen)
|
|
What do the muscles do with glucose?
|
Glycolysis - which generates pyruvate first before TCA.
|
|
What do muscles do with Pyruvate?
|
If O2 available, TCA cycle.
If O2 unavailable, convert to lactate and alanine - less ATP gets made, but NAD+ regenerated. |
|
What happens to Lactate and Alanine?
|
They're sent to the liver
|
|
What does the liver do with Lactate and Alanine?
|
Use it to remake pyruvate for gluconeogenesis
|
|
Which steps of gluconeogenesis require ATP?
|
-Pyruvate -> oxaloacetate
-Oxaloacetate -> PEP -PEP -> Glucose |
|
How does the liver generate ATP?
|
By breaking down fat -> AcCoA and using that for the TCA cycle
|
|
What is this shuttling of pyruvate breakdown products from skeletal muscle to liver called?
|
The cori cycle
|
|
How can the liver still run the TCA cycle when muscles are unable to b/c of anaerobic conditions?
|
The liver has more O2 in general.
|