ch 16 (no CAC steps)

what are the three stages of cellular respiration

1. acetyl CoA production

2. acetyl CoA oxidation

3. e- transfer and oxidative phosphorylation

products of stage 1

ATP, NADH, FADH2

from breakdown of amino acids, fatty acids, glucose

products of stage 2

NADH, FADH2, one GTP

citric acid cycle

products of stage 3

lots of ATP

how does pyruvate get into mitochondrial matrix for CAC

mitochondrial pyruvate carrier (MPC)

H+ coupled pyruvate specific symporter in inner MMemb

what kind of reaction does PDH complex catalyze

oxidative decarboxylation

what are the parts of the PDH complex

3 enzymes: pyruvate dehydrogenase (E1) dihydrolipoyl transacetylase (E2) dihidrolypoyl dehydrogenase (E3)

5 coenzymes: TPP, lipoate, CoA-SH, FAD, NAD

role of coenzyme A

reactive thiol group is acrylic carrier, forms thioesteer with acetate in acetyl CoA

role of lipoate

electron (hydrogen) carrier, acyl carrier

what is substrate channeling

passage of intermediates from one enzyme to another without release

isolated mitochondria contain the enzymes/coenzymes/protiens needed for what processes

citric acid cycle, electron transfer and ATP synthesis via oxidative phosphorylation, oxidation of fatty acids and AA to acetyl CoA, oxidative degradation of AA to CAC intermediates

what are the products of the CAC

2 CO2

3 NADH

1 FADH2

1 GTP→ATP

complete oxidation of _______ to ________ extracts the maximum potential energy

acetyl CoA to CO2

carbonyl groups are more ________ ________ than a methylene/methane

chemically reactive

the CAC accepts how many carbon skeletons

3, 4, and 5

deaminated aspartate yields

oxaloacetate

deaminated glutamate yields

alpha-ketoglutarate

amphibolic pathway

serve in both catabolic and anabolic processes

CAC is an example of this

animals cannot convert acetate or acetyl CoA to ______

glucose

glyoxylate cycle

reaction sequence that converts acetate to carbohydrate

bacteria, plants, fungi, protists

anaplerotic reactions

chemical reactions that replenish intermediates

pyruvate carboxylase

reversible carboxylation of pyruvate by HCO3- to form oxaloacetate

most important anaplerotic reaction in mammalian liver, kidney, brown adipose

requires ATP energy

allosterically activated by acetyl CoA

what does biotin do

vitamin, specialized carrier of one carbon groups (CO2) in carboxylation reactions (adding carbons)

prosthetic group of pyruvate carboxylase

two steps in carboxylation of pyruvate occur at separate active sites. arm of biotin transfers activated carboxyl groups from first to second active site

examples of biological tethers and what are they for

lipoate, biotin, pantothenate

substrate channeling that move intermediates from one active site to the next

where is CAC regulated

PDH complex, citrate synthase, isocitrate dehydrogenase complex, alpha-ketoglutarate dehyudrogenase complex

what are the three strongly exergonic steps of CAC that are regulated

citrate synthase, isocitrate DH, alphaketoglutarate DH

what activates PDH

high energy demand: AMP, NAD+, Ca2+

CoA

what inactivates PDH

ample fatty acids & acetyl CoA (fuel)

high ATP & NADH

what activates PDH kinase (inactivate PDH)

ATP, NADH, acetyl CoA

what inactivates PDH kinase (activate PDH via PDH phosphorylated)

ADP, NAD+, pyruvate

what activates citrate synthase

ADP

what inactivates citrate synthase

ATP, NADH, succinylCoA, citrate

what activates isocitrate DH

Ca2+, ADP

what inactivates isocitrate DH

ATP

what activates alphaketoglutarate DH complex

Ca2+

what inactivates alphaketoglutarate DH complex

succinylCoA, NADH

oncogenic mutations cause…

downregulation of MPC

inactivation of PDH

inactivation of succinctness dehydrogenase

why do tumors have the effects they do on CAC

tumors like fermentation

want to accumulate biomass

oncometabolites

stimulate tumor growth by acting thru specific GPCRs in plasma membrane

tumor cells accumulate oncometabolites - lactate and succinct → good intermediates to synthesize larger molecules, increase biomass

mutations in what CAC enzymes cause tumors? which means they are defined as what?

succinate DH, fumarase

tumor suppressors

glial cell tumors have mutant _____________ __________

NADPH-dependent isocitrate dehydrogenase

effects of mutated isocitrate DH

cannot convert isocitrate to alphaketoglutarate, convert alphaketoglutarate to 2-hydroxyglutarate

2-hydroxyglutarate inactivates histone demethylase, causes change in gene expression that allows tumor cell growth

what are metabolons and give examples

integrated multi enzyme complexes that are held together by noncovalent interactions

malate dehydrogenase, citrate synthase, aconitase constitute a metabolon

effect of malonate on CAC

competitive inhibitor of succinate dehydrogenase → prevent formation of succinate, leads to accumulation of acetyl CoA