Biochem 501 Exam 3 UW Madison

Anabolism

Metabolic pathways that construct molecules, requiring energy.

Where does the body get energy (from sugars) while in unfed state

Glycogen -> Glucose-6-Phosphate-> Energy

Where does the body get energy (from fats) while in unfed state

Fat -> Acetyl CoA -> Ketones

Activated Carrier of phosphate

ATP (favorable)

Activated Carrier of electron

NADH/FADH2

Activated Carrier of acyl groups

Coenzyme A

Signal transduction

Cells receive, process and respond to info in their environment

What is the signal in the body?

Hormones

What is the signal transduction process?

signal -> receptor -> Amplification -> Transduction -> Response

What is the general idea of the fasted state?

Low blood glucose, alpha cells in pancreas release glucagon

Glucagon

peptide hormone, turns on fuel production

What does the body do for use of fat?

turns fat into acetyl coA

general steps of gluconeogenesis

1. Phosphorylase (Pi+Glycogen-> Glucose 1-Phosphate)

2. De-branching Enzyme

3. Phosphogulcomutase (G1P <-> G6P)

4. Glucose-6 Phospotase (G6P -> Glucose in ER Lumin)

G-Protien response to glucagon

Trades GDP for GTP, beta and gamma subunits dissociate, alpha subunit binds to Adenylase Cyclase to form cyclic AMP

what happens after cyclic AMP is formed?

cAMP activates Protein Kinase A

What happens to Protein Kinase A after activation?

cAMP binds to regulatory subunits which dissociate from the catalytic subunits, PKA then adds phosphate (activates) to phosphorylase kinase, hormone sensitive lipase, and fructose 2,6-Bisphosphate

What does hormone sensitive lipase do?

catalyzes hydrolysis of fatty acids (fatty acids bound to serum albumin in bloodstream)

Gluconeogenesis products

2 pyruvate -> Glucose (in the liver)

Gluconeogenesis costs

2 NADH, 4 ATP, 2 GDP

Step 1 of gluconeogenesis

Pyruvate into Phosphoenolpyruvate, catalyzed by pyruvate carboxylase (Pyruvate + CO2 + ATP +H20 -> Oxaloacetate, ADP, Pi, 2 H+

Step 2 of gluconeogenesis

Oxaloacetate reduced to malate and transfered to cytoplasm by Phsophoenolpyruvate Carboxykinase (OAA -> Malate -> Cytoplasm -> Reduced back to OAA and generates NADH+ used later in gluconeogenesis)

Step 3 of gluconeogenesis

Fructose 1,6-biphosphate -> F6P by F16Phophotase (allosteric enzyme)

Step 4 of gluconeogenesis

G6P hydrolized by G6Phosphotase (G6P -> Glucose + Pi)

F-2,6BP

-Activates PFK1 (turns on glycolysis)

-Inhibits FBPase-1 (turns off gluconeogenesis)

PFK2/FBPase2

Two functions

-Produce F-2,6BP by using kinase to add Pi group

-Take Pi group off F-2,6BP by using phosphotase

How long after last meal do Ketone Bodies get produced?

After about 2 days

-CAC Slowed (OAA used in gluconeogenesis)

-Acetyl-CoA builds up, forms ketone bodies

How is Acetyl CoA used to form ketone bodies

3 Acetyl CoA's used to form ketone bodies

Transport Types

passive and active

passive transport

-Simple diffusion

-Facilitated diffusion (needs a protein)

-No energy required goes through gradient

active transport

Against gradient

-primary (requires energy)

-secondary (uses gradient made by primary active transport)

Glucose transport

-GLUT work via facilitated diffusion

-Kt=1/2 Vmax, lower Kt=Faster Transporter

Insulin release

-Glucose into beta cells through GLUT2, convert to pyruvate then oxidized to CO2 + H2O

-Increase in ATP, closes K+ Channel, then opens Ca2+ Channel, increase Ca2+ stimulates the release of insulin

Binding of insulin activates enzyme via autophosphorolation

Results in

-Stimulate movement of GLUT4 to plasma membrane

-Activation of Phosphoprotein Phosphotase (PP1)

-Modulate gene expression in cell growth and biosynthesis

Glycogen Systhesis

Glucose -> G6P -> Glycogen

Steps of Glycogen synthesis

1. G6P -> G1P (phosphoglucomutase)

2. G1P + UTP + H20 -> PPi + UDP Glucose (driven by PPi + H2O -> 2Pi)

3. UDP Glucose -> Glycogen (n residues)

Fates of G6P

-Insulin signal

-Glycolysis (to pyruvate)

-Penta Phosphate Pathway (PPP) (into 5 carbon sugar phosphates)

Oxidative phase of PPP

-2 NADPH Formed

-G6P -> 6-Phosphogluconolactone( by G6P DHase) -> Ribose 5 Phosphate

-Non-reversible

-Generates

Non-Oxidative PPP

3 pentophosphate -> 2 F6P + glyceraldehyde3-phosphate

Needs of Cells

1. R5P Needed more than NADPH

-Only non-oxidative, since oxidative generates NAPDH

2. Equal Needs of NADPH and R5P

-Only oxidative since both are made in that pathway

3. Need for NADPH more than R5P

-Oxidative on to make NADPH, non oxidative on to produce G6P which is used in oxidative to make NADPH

4. NADPH and ATP needed

-Oxidative to make NADPH

-Non oxidative to fuel glycolysis -> ATP

Which compound is used to synthesize fatty acids?

Acetyl CoA

Three stages of fatty acid synthesis

1. Acetyl CoA is moved from mito -> cytoplasm (in the form of citrate then form acetyl coa again, OAA can be made and can generate NADPH

2. Activation of Acetyl CoA

-RDS, takes CO2 + Acetyl CoA -> Malonyl CoA

3. Repetitive Addition

step 1 of FA synthesis

-Form citrate in condensation reaction to move Acetyl Coa to cytoplasm

-Citrate -> Acetyl Coa + OAA (requires ATP)

-Needs NADPH so oxidative PPP on

Step 2 FA synthesis

Acetyl CoA Carboxylase catalyzes this step (RDS)

-CO2 + Acetyl CoA (2C)+ ATP -> Malonyl CoA (3C)

Acetyl CoA carboxylase regions

Biotin Carrier protien gets HCO3 (C02) and goes to transferase region and adds CO2 to acetyl CoA

step 3 of FA synthesis

-Catalyzed by FA Synthase (condensation, reduction, dehydration all done by this enzyme)

-2 Carbons at each step, uses NADPH for e- source

1. ACoA + Malonyl CoA -> 4C +CO2

2. 4C + NADPH -> adds C-H bond to carbons

3. Form water and alkene

4. reduction by NADPH gives alkane, release of palmitate (16C) by hydrolysis

Triaceylglycerol vs Phospholipids

-TAG for slow/ no growth

-PL for rapid growth (used in cell membranes)

-Both TAG and PL synthesis start with Phosphatidate

Phosphatidate

Pamitate (16C) + Oleic acid (18C) +G3P + ATP -> Phosphatidate