Lecture 11 Overview of CHO Metabolism II Part B Flashcards
What is a major gateway molecule driving the CAC?
pyruvate
How is pyruvate made accessible in the mitochondria?
It is converted to Acetyl-CoA by the pyruvate dehydrogenase (PDH) complex.
What is the metabolic fates of pyruvate?
- aerobic conditions
- anaerobic conditions (homolactic fermentation)
- alcoholic fermentation
What happens to pyruvate under aeorobic conditions?
pyruvate carbons are converted to Acetyl-CoA via PDH and then oxidized to CO2 by the CAC and the electrons are eventually transferred to yield H2O in oxidative phosphorylation.
What happens to pyruvate under anaerobic conditions?
pyruvate is reversibly converted to lactate & alanine. During situations of exerting muscles beyond the VO2max glycolysis is being asked to work faster than the CAC forming a build up of pyruvate which turns into lactate or alanine in order to get rid of it.
What substrates are increased in working muscle to cause lactate?
NADH, Pi and ADP (AMP) are ↑ in working muscle, stimulating glycolysis and ↑ pyruvating leading to lactate formation, regenerating NAD+
homolactic fermentation
What happens to pyruvate in yeast?
fermentation → converted to CO2 and ethanol
What substrate is central to pyruvate reaction?
nicotinamide adenine dinucleotide + hydrogen (NADH and NAD+) are central to these reactions for electron movement
How is pyruvate converted to lactate?
Via the enzyme lactate dehydrogenase and uses the conenzyme NADH to regenerate NAD+
What is the purpose of converting pyruvate to lactate?
Essentially when the body is in a high energy need, glycolysis and CAC become uncoupled and the high rate of glycolysis leads to a desparation for NAD+. The NADH which is generated in step 6 of glycolysis can be converted back to NAD+ in the reaction that generate lactate from pyruvate. This reaction assures a steady supply of NAD+ which allows for the continued operation of step 6 and the continued production of ATP even under conditions of redcued oxygen availabilty.
What is the amount of ATP produced in anaeorbic vs. aerobic conditions?
rate of ATP formation via glycolysis is about 100x faster than ox. phos.. thus the need for more NAD+ when glycolysis and CAC are uncoupled
What is the primary conversion of pyruvate?
Cori cycle
Lactate from anaeorbic metabolism of glucose is taken to the liver because where it may be used for gluconeogensis to replenish plasma glucose. so the lactate is converted right back into pyruvate which also regenerate NADH for gluconeogenesis
What is the secondary conversion of pyruvate?
alanine cycle (protein source of energy)
with high energy demand muscle protein gets broken down to amino acids so the pyruvate and amino acids will leave the tissue as alanine and be taken up by the liver where the pyruvate may be used for gluconeogensis and the amino group converted to urea for excretion (detoxification of NH4)
Where are lactate and alanine generated?
peripheral tissue
What is the ultimate purpose of the cori cycle and alanine cycle?
The lactate and alanine produced from pyruvate in the peripheral tissue can be converted back into glucose in the liver and recycled back to the tissue via blood.
What does pyruvate entering the CAC depend on?
- availability of oxygen: aerobic vs. anaeorbic
- metabolic state of the cell
How is G6P produced?
- phosphorylation of free glucose
- glycogen degradation
- gluconeogenesis
How is pyruvate transported into the mitochondria?
pyruvate is adjunct so it is transported into the mitochondria by pyruvate translocase monocarboxylate carrier
What happens to pyruvate once in the mito matrix?
pyruvate converted to Acetyl CoA by PDH complex (many cofactors dervied from B vitamins - FAD, TPP, thiamin pyrophosphate)
regulation of PDH
tightly regulated via product inhibition (acetyl CoA, NADH, ATP) & covalent modification (phosphorylation)
Main purpose of CAC
Acetyl CoA → 2 CO2
Acetyl groups derived from CHO, aa, FAs enter the CAC where they are oxidized to CO2
Regulation of the CAC
- points of inhibition
- central role of NAD+ requirements can inhibit if not available
- excess NADH will also suppress
- ADP and Ca2+ are activators
How does mitochondrial density differ between cells?
Cells requiring greater respiration (CAC) have more mitochondria
* ~50% of cardiac myocyte volume
* Skeletal muscle variable depending on needs
How does mitochondrial cristae vary?
cristae in compartment can also vary and regulate rate of respiration (surface area) by trying to block in certain substrates in order to control particular reaction in a localized manner
* Premise is closed compartment to generate concentration gradient for movement of protons to drive ATPase
What transport happens within the mitochondrial inner membrane?
controlled im-permeability of the inner membrane sufficiently generates concentration gradients (outer membrane permeable)
* only e- from NADH are ‘transported’ into inner membrane via malate-aspartate shuttle
* Ca movement is regulated by ports and is sensitive to cytosolic [Ca]
* ADP-ATP translocator (Ancp); must have both side bound to change conformation
What happens in the ETC?
oxidative phosporylation chain of rxs located in the inner mitochondrial membrane (ADP + Pi = ATP)
* Free energy from electrons is used to pump H+ into inter-membrane space = electrochemical gradient (low to high) ⇝ energy created from H+ coming back used to form ATP bond
general summary of ox. phos.
Describe the PPP
A secondary pathway of glucose oxidation occuring in the cytosol used to generate NADPH and ribose-5-phosphate
What is NADPH and ribose-5-phosphate produced from PPP important for?
- NADPH: anabolic reactions used to form FAs, sterol & cholesterol (wants to donate e-)
- ribose-5-phosphate: essential for nucleotides and nucleic acids
What does PPP pathway depend on?
need for NADPH, ribose-5-phosphate & ATP
What uses the PPP?
- RBCs
- adipocytes
- liver
- mammary gland
How does PPP reconnect with glucose?
Excess R5P is converted to glycolytic intermediates by a sequence of reactions that can operate in reverse to generate additional R5P if needed
Other terms for PPP?
- phosphogluconate pathway
- hexose monophosphate shunt
- pentose shunt
What are the two phases of PPP?
- oxidative phase: NADPH production
- non-oxidative phase: ribose-5-phosphate production
What is another important role of the PPP?
important for anti-oxidant defence
