Last Deck is Always the Hugest Flashcards
What’s the TCA Cycle specifically looking for?
2-carbon units
Describe E1 of PDH
It’s Pyruvate Dehydrogenase, 24 chains, TPP is it’s prosthetic group, and it catalyzes oxidative decarboxylation of pyruvate
Describe E2 of PDH
Dihydrolipoyl Transacetylase, 24 chains Lipoamide Prothetic Group, and catalyzes transfer of acetyl group to CoA
Describe E3 of PDH
It’s Dihydrolipoyl Dehydrogenase, 12 chains long, FAD prosthetic group, and it regenerates the oxidized form of lipoamide
What keeps PDH functioning so well
It’s proximity of all enzymes increases reaction rates and keeps all intermediates bound. The flexible E2 arm calls on each active site in turn.
Step 1 of PDH Cycle?
Pyruvate enters
CO2 Leaves. TPP group in E1 chamber Bonds with the…Acetyl group?
Step 2 of PDH Cycle?
Lipomyl arm swings into TPP E1 group
Step 3 of PDH Cycle?
Lipomyl arm swings the acetyl group into the E2 group
Step 4 of PDH Cycle?
CoA enters, Acetyl CoA group leaves, and Oxidized Lipomyl Arm Swings into E3 FAD group
Step 5 of PDH Cycle?
Regnerated Lipomyl Arm leaves the E3 “chamber”, but now FAD has become FADH2
Step 6 of PDH Cycle?
NAD+ Comes along and NADH and H+ leaves to set it back to the original FAD and PDH is ready again
What inhibits and activates PDH?
- PDH is regulated allosterically by reverse phosphorylation.
- Also, High acetyl CoA directly inhibits E2
- Phosphorylated PDH is inactive PDH. Dephosphorylation occurs through phosphotase at the expense of H2O.
- ATP activates KINASE which Deactivates PDH.
- So Indirectly, High Levels of ADP might Indirectly keep PDH active. Same for Pyruvate. High levels of pyruvate activates phosphatases which activate PDH.
- NAD also indirectly activates PDH
- Indirect Inhibitors can include NADH, Acetyl CoA, and ATP.
Describe the “3rd” Step of the TCA Cyle
- Starting with an Alpha Keto-Glutarate
- Enzyme alpha-ketoglutarate deydrogenase complex
- NAD+ and CoA is taken in.
- NADH, H+, and CO2 leaves
- Succinyl CoA is formed.
- This step is Very similar to PDH.
- Both reactions decarboxylate an alpha-ketoacid and create a thioester linkage with CoA
One More Time, just to hammer this bitch home,
Name all of the Activators that assist in sending PDH to it’s INACTIVE state…(PHOSPHORYLATED)
Inhibitors?
Activators:
- Acetyl CoA
- NADH
- ATP
Inhibitors:
- ADP
- Calcium
- Pyruvate
- CoA
- NAD+
- H+
Now…What are the acivators and inhibitors in sending inactive PDH into it’s ACTIVE state?
Activators:
- Calcium
- Magnesium
- NAD+
- CoA
- Insulin
- H+
Inhibitors:
- NADH
- Acetyl-CoA
Describe the “4th” step of the TCA cycle
- Start with Succinyl CoA
- Enzyme Succinyl CoA Synthetase
- GDP and Pi come in
- GTP and CoA leave
- Product is Succinate.
- This is the only step in the cycle that has a GTP product
- Succinyl CoA contains a high energy thioester bond (Similar to ATP)
Describe the 5th Step of the TCA Cycle
- Starting with Succinate
- Enzyme Succinate Dehydrogenase
- FAD comes in,
- FADH2 comes out
- Product is Fumarate
- This Fumarate step is apparently quite useful because it produces FADH2. Which we use elsewhere.
Describe the “2nd” Step of the TCA Cycle
Why didn’t we start with this one? I dunno.
- Starting with Isocitrate
- Enzyme Isocitrate Dehydrogenase
- NAD+ Comes in,
- NADH and H+ Come Out
- Intermediate Product is oxalosuccinate.
- From there, H+ enters, (yes that’s right)
- CO2 leaves
- Ending product is alpha-ketoglutarate
- This one is the first major allosteric control point.
- ADP Activates
- ATP and NADH Inhibit
Describe the 1st step of the pentose phosphate pathway
- Starting with G-6-P
- Enzyme Glucose 6-phosphate dehydrogenase
- 2 NADP+ enters,
- 2 NADPH and CO2 leave (I think 2 CO2)
- Product is Ribulose 5 phosphate
- PPP Synthesizes Pentoses such as ribose and deoxyribose
- NADPH for reductive biosynthesis such as cholesterol, and glutathione
- This first step is the rate limiting step
Why are there multiple modes available for the PPP?
Producing NADPH from G6P is an oxidative process, however from F6P, one can nonoxidatively produce Ribulose 5 phosphate without producing any NADPH. This is a Nonoxidative Process.
- Sometimes we need one more than the other
When is Mode 1 of PPP used?
When much more Ribose 5 phosphate than NADPH is required, we skip the oxidative step and product Ribose 5-phosphate from Fructose 6 phosphate
When is Mode 2 of PPP used?
When an equal number of NADPH and Ribose 5-phosphate are required,
- The Normal Mode. Oxidatively converts G6P to Ribulose-5-phosphate producinig 2 NADPH
When is Mode 3 of PPP Used?
When More NADPH than R5P is required
- In this step, R5P is converted into Glyceraldehyde 3 phosphate, which sends that up the chain to Produce more G6P.
- From there, another oxidative cycle of producing NADPH can occur.
When is Mode 4 of PPP Used?
When there is a need for both NADPH and ATP.
- Similar to Mode 3, R5P is converted to Glyceraldehyde 3-phosphate.
- Glyceraldehyde 3 phosphate goes down the glycolysis chain to produce more Pyruvate (Gaining 2 ATP)
Describe what disorder is found in the Pentose Phosphate Pathway
- Not sure what this deficiency is called…
- But it’s X-linked. So more men get it.
- Causes Hemolytic Anemia because of Deficient levels of NADPH in red cells.
- I guess it’s just called G6PD deficiency, or Glucose 6 phosphate dehydrogenase deficiency
- So in failing to produce NADPH because of shitty enzymes…
- This shitty enzyme is inhibited by low levels of NADPH. It’s supposed to be activated I think.
- Without NADPH, Glutathione reductase can’t reduce Oxidized Glutathione (GSSG) down to Reduced Glutathione (GSH).
- Reduced Glutathione is needed to maintain healthy red cell membranes
Describe’s insulin’s effect on Glucose
- Activates Glucose (GLUT4), causing increased glucose uptake in muscle and adipose
- Activates Glucokinase, which increases glucose uptake in the liver
Describe insulin’s effect on glycogen
- Activates Glycogen Synthase, which increases glycogen synthesis in the liver and muscle
- Inhibits Glycogen Phosphorylase, Which in turn Decreases Glycogen Breakdown in the liver and muscle.
Describe insulin’s effect on glycolysis
Activates PFK-1 (by PFK-2), and activates PDH complex, which increases Glycolysis and Acetyl-CoA production in the liver and muscle.
Describe insulin’s effect on fatty acids
- Activates Acetyl CoA Carboxylase, which increases fatty acid synthesis in the Liver.
- Activates Lipoprotein Lipase, which increases Triacylglycerol synthesis in adipose tissue.
What can an insulin deficiency or resistance cause?
Hyperglycemia, metabolic syndrome, and diabetes
Describe the Physiological effects of epinephrine
Increases Heart Rate
+ Increases Blood Pressure
+ Increases Dilation of Respiratory Passages
= Increased delivery of Oxygen to muscle tissues
Describe the metabolic effects of epinephrine pertaining to Glucose
Increases:
- Glycogen Breakdown in the muscle and Liver
- Gluconeogenesis in the liver
Decreases:
- Glycogen Synthesis in the muscle and liver
Overall: Increases Production of Glycose for Fuel
Describe the metabolic effects of epinephrine pertaining to ATP
Increases Glycolysis in the muscle,
which increases ATP production in the muscle
Describe the metabolic effects of epinephrine pertaining to fatty acids.
Increases Fatty Acid Mobilization in adipose tissue
Which increases availability of fatty acids as fuel
Describe the metabolic effects of epinephrine influence other hormones
I may have worded that question wrong but…
- Increases Glucagon Secretion
- Decreases Insulin Secretion
Which overall reinforce the metabolic effects of epinephrine.
Describe Glucagon’s effects on glycogen?
- Activatess Glycogen Phosphorylase (Which increases Glycogen breakdown in the liver into glucose)
- Inhibits Glycogen Synthase (Which decreases glycogen synthesis in the liver so less glucose is stored as glycogen)
