2 Types of Cofactors
essential ions and coenzymes
Coenzyme examples
hydrogen, electrons
Coenzymes act as
group transfer reagents
Where can larger mobile metabolic groups attach on the coenzyme
reactive center
How are coenzyme rxns organized?
types of substrates and mechanisms
2 types of essential ions
Activator ions (loosely bound) and metal ions of metalloenzymes (tightly bound)
2 types of coenzymes
cosubstrates (loosely bound) and prostetic groups (tightly bound)
metal-activated enzymes
enzymes that have an absolute requirement or are stimulated by metal ions (examples: K+, Ca2+, Mg2+)
metalloenzymes
enzymes that contain firmly bound metal ions at the enzyme active sites (examples: iron, zinc, copper, cobalt)
How many electrons are oxidized by pyrdine nucleotides at one time?
2
NAD and NADP are ___ for dehydrogenases?
cosubstrates
What do dehydrogenases transfer from a substrate to pyridine ring c-4 of NAD+ or NADP+?
a hydride ion (H:-)
Net reaction from dehydrogenase?
NAD(P)+ + 2e- + 2H+ --> NAD(P)H + H+
Iron undergoes reversible oxiation and reduction... What is the reaction?
Fe3+ + e- (reduced substrate) --> Fe2+ + (oxidized substrate)
Enzyme ___ groups and ____ contain iron.
Enzyme heme groups and cytochromes contain iron
_______ _____ exists in iron-sulfer clusters.
Nonheme iron exists in iron-sulfur clusters. Iron is bound by sulfide ions and S- groups from cysteines.
Iron-sulfer clusters can accept how many electrons in a reaction?
One
Iron atoms are complexed with _________ sulfide ions (S 2-) and with _____ groups of Cys side chains
Iron atoms are complexed with an equal number of sulfide ions (S 2-) and with thiolate groups of Cys side chains .
Cosubstrates
Coenzymes that are altered during the rxn and regenerated by another enzyme
Prosthetic groups
Coenzymes that remain bound to the enzyme during the rxn and may be covalently or tightly bound to enzyme
Metabolite Coenzymes
coenzymes that were synthesized from common metabolites (examples: ATP and other nucleoside triphosphates)
Vitamin-derived coenzymes
coenzymes that are derivatives of vitamins (outside intake)
What can ATP donate?
(1) Phosphoryl group (g-phosphate)
(2) Pyrophosphoryl group (g,b phosphates)
(3) Adenylyl group (AMP)
(4) Adenosyl group
SAM Synthesis
SAM (S-Adenosyl methionine) is synthesized by ATP and methionine. SAM is used for methyl transfer reactions (examples: synthesis of epinephrine from nonepinephrine).
Methionine + ATP -> S-Adenosylmethionine + Pi +PPi
Metabolism
Oxidation of reduced fuel (glucose) to generate energy in the form of ATP and NAD(P)H. Electrons are falling down an electrical potential gradient from reduced (glucose) to oxidized (oxygen).
Cells are a system in a ____ that want to maintain _____.
Cells are systems in a dynamic steady state that want to maintain homeostasis.
ATP Vs NADH
ATP is fast, high E storage fuel. NADH and other reducers are sources of reducing power.
NAD(P)H
NAD(P)H is the common redox agent/electron carrier. NADPH is for biosyntesis (build stuff)
NADH
NADH burns energy. NADH is metabolism and breakdown.
What organ carries out all metabolic processes?
liver
How can you activate molecules?
You activate molecules by adding phosphate on them --> make them more able to react.
What happens if you intake lots of glucose?
If you have a lot of glucose, you can put some in storage so cells make it into glycogen.
What cell metabolism processes happen in the cytosol?
Fatty acid synthesis, glycolysis, most gluconeogeneisis, PPP
What cell metabolism processes happen in the Mitochondrion?
Krebs cycle, oxidative phosphorylation, fatty acid breakdown
What cell metabolism processes happen in the golgi apparatus?
sorting and secretion of some proteins
What cell metabolism processes happen in the endoplasmic reticulum?
deliver of proteins, synthesis of lipids for membranes
What cell metabolism processes happen in the nucleus?
nucleic acid syntheisis
Reciprocal regulation of metabolic pathway enzymes
Activation of one mode is accompanied by reciprocal inhibition of the other mode
Glucose becomes what after glycolysis?
2 pyruvates
Pyruvate can be further metabolized to what?
Lactate/ethanol in anaerobic conditions.
Acetyle CoA in aerobic conditions.
Acetyle CoA oxidizes to what in the CAC?
CO2 and H2O
Net rxn of glycolysis?
Glucose + 2 ADP + 2 NAD+ + 2 Pi --> 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Why do enzymes which use ATP need Mg++?
Mg stabilizes
What substrates can hexokinases act on?
Can phosphorylate glucose, mamnose, and fructose
What happens to heokinase in yeast?
Yeast hexokinase undergoes an induced-fit conformational change when glucose binds
What are the isozymes of hexokinase and when are they used?
Hexokinase I,II, and III are in normal glucose concentrations. At high glucose levels hexokinase IV.
What is the first committed (non-reversible) step of glycolysis?
When PFK-1 phosphorylates the C-1
What is an allosteric inhibior of PFK-1?
ATP, ADP, AMP, elevated levels of citrate, Fructose 2,6-bisphosphate
Substrate level phosphorylation in glycolysis
Steps 6 and 7 couple oxidation of an aldehyde to a carboxylic acid with the phosphorylation of ADP to ATP
Pyruvate Kinase
PK catalyzes a substrate-level phosphorylation and is metabolically irreversible. Regulation both by allosteric modulators and by covalent modification (hormones and nutrients)
Pyruvate to Ethanol
Yeast- anaerobic
Pyruvate decarboxylase takes pyruvate and makes it acetaldehyde. Then alcohol dehydrogenase takes acetaldehyde and makes it ethanol
Why must you go through anaerobic or aerobic respiration?
need to get rid of electrons or they will build up
Pasteur effect
slowing of glycolysis in the presence of oxygen
Pyruvate to Lactate
Muscle lactate dehydrogenase converts pyruvate to lactate and regenerates NAD+ for use by GAPDH in glycolysis.
Glucose + 2 Pi2- + 2 ADP3- -->2 Lactate- + 2 ATP4- + 2 H2O
Pyruvate decarboxylase
in microbes decarboxylates pyruvate to make acetaldehyde (which will become ethanol)
Pyruvate dehydrogenase
When OXYGEN is present (aerobic): decarboxylates pyruvate to form acetyl-CoA for TCA cycle
Pyruvate carboxylase
adds CO2 to pyruvate to make oxaloacetate for anapleurotic reactions and for gluconeogenesis
When is glycolysis activated?
when atp is needed
Regulation of hexose transporters
Glucose enters mammalian cells by passive transport down a concentration gradient from blood to cells. GLUT is a family of six passive hexose transporters. Glucose uptake into skeletal and heart muscle and adipocytes by GLUT 4 is stimulated by insulin. Ot
Regulation of Hexokinase
G6P (product) levels increase when glycolysis is inhibited at sites further along in the pathway. G6P inhibits hexokinase isozymes I, II and III. Glucokinase forms G6P in the liver (for glycogen synthesis) when glucose is abundant (activity is modulated b
Anapleurotic Rxns
many of the intermediates of the TCA can be synthesized by other enzymes and fed into the TCA to refill it
Acetyle CoA -->
fatty acids
alpha-ketoglutarate -->
glutamate
succinyl CoA -->
delta-aminolevulinate
Fumarate/oxaloacetate -->
Aspartate
What are the organic electron carriers?
NAD(H), FAD(H2), FAD, FMN, NAD(P)
Reduction Potential
relative ability to give or accept electrons
-more negative means more likely to give up electons
- more positive means more likely to accept
NHE
normal hydrogen electron (reduction potential is meansured realtive to NHE)
ETC Net rxn
NADH (reductant) + H+ + O2 (oxidant) --> NAD+ + H2O