Part 1 Chiropractic Boards: Biochemistry -- Cycles & Metabolism

What is the different in general between NAD & NADH function?

NAD = breaks molecules

NADH = builds molecules

For oxidation/reduction reactions, which part increases positive charges or the loss of negative charges? Which one is the addition of the hydrogen and gain of the electrons?

Oxidation

Reduction

(OIL RIG -- oxidation is loss (of e-), reduction is gain (of e-)

What are the 4 major catabolic pathways?

1) Glycolysis

2) Pyruvate oxidation

3) Citric Acid Cycle (Krebs, TCA)

4) Oxidative phosphorylation

What are the rate limiting steps for each of these reactions:

Kreb's Cycle

HMP shunt

FA synthesis

Beta Oxidation

Urea Cycle

Krebs = Isocitrate DH

HMP shunt = G6P DH

FA synthesis = Acetyl CoA carboxylase

B-ox = Carnitine acyltransferase I (CAT)

Urea = Carboamoyl phosphate synthase I

Rule of thumb: Substrates _________ a reaction while products __________ a reaction.

stimulates

inhibits

Steroids regulate the rate of enzyme synthesis at the ____ level

DNA level

What is glycolysis? Where does it occur?

Breakdown of glucose by enzymes, releasing energy and pyruvic acid.

Occurs in CYTOSOL

NOTE: Acronym for remembering enzymes in glycolysis = HIPA IDK MEK

What is the net production of glycolysis?

1 glucose = 2 pyruvate = 2 ATP & NADH

What is the first step of glycolysis? What enzyme is used?

Glucose --> Glucose 6P

Enzyme = Hexokinase

(HIPA IDK MEK)

What is the second step of glycolysis?

Glucose 6P --> Fructose 6P

What is the third step of glycolysis? What is the enzyme?

Fructose 6P --> Fructose 1-6BP

Enzyme = PFK

(HIPA IDK MEK)

What is the 4th step of glycolysis?

Fructose 1-6BP --> DHAP + Glyceraldehyde 3P (G3P)

What is the 5th step of glycolysis?

DHAP <--> G3P

What is the 6th step of glycolysis?

G3P --> 1,3 BPG

What is the 7th step of glycolysis?

1,3 BPG --> 3 phosphoglycerate

What is the 8th step of glycolysis?

3 phosphoglycerate --> 2 phosphoglycerate

What is the 10th & last step of glycolysis? What is the enzyme?

PEP --> Pyruvate

Enzyme = Pyruvate Kinase

(HIPA IDK MEK)

What is the 9th step of glycolysis?

2 phosphoglycerate --> PEP

Which steps of glycolysis use ATP? Create ATP?

Used = Step 1 & 3

(hexokinase & PFK)

Created = Step 7 & 10

(Phosphoglycerate kinase & Pyruvate kinase)

NOTE: All the kinase enzymes in glycolysis will use/create ATP; use in the first half, create in the second half

What step of glycolysis uses NAD+ and converts it to NADH?

Step 6 (G3P --> 1,3BP)

NOTE: The only dehydrogenase enzyme in all of glycolysis is the one involved with NAD+

What are the 6 enzyme regulating inhibitors of glycolysis?

1) ATP (high energy charge)

2) NADH or FADH2

3) Very low pH (lactate)

4) Citrate

5) Low Blood Glucose

6) Glucagon

What are the 4 enzyme regulation stimulants?

1) AMP or ADP

2) NAD+ or FAD+

3) Fructose 2,6 BP

4) NH3 (ammonia)

What is the livers version of hexokinase (1st step of glycolysis)? In what two ways does it differ?

Glucokinase

1) Lesser affinity for glucose (higher Km)

2) NOT inhibited by G6P

In lactic acid production, what is the enzyme used to convert pyruvate to lactate? What is regenerated through this and why is it important?

Lactate Dehydrogenase

NAD+ regenerated

-- needed to continue running glycolysis

-- making lactate buys time and allows temporary overrunning of glycolysis

In alanine production, what is the enzyme used to convert pyruvate to alanine? What is scavenged for and why is this important?

Alanine Aminotransferase (pyruvate + NH3 --> alanine)

NH3 is scavenged

- produced by AA entering Krebs cycle

- making alanine allows cell to get RID of NH3 and send to liver as a glucogenic substrate

How does fructose enter glycolysis?

Fructose --> Fructose 1P --> DHAP + Glyceraldehyde --> DHAP + G3P

DHAP & G3P

How does Galactose enter glycolysis?

Galactose --> Galactose 1P (+ UDP Glucose) --> Glucose 1P + UDP Galactose --> UDP Glucose (returns to cycle to react with galactose 1P and make our desired product)

Glucose 1P

What is the Kreb's cycle?

second stage of cellular respiration, in which pyruvic acid is broken down into carbon dioxide in a series of energy-extracting reactions

Where does the Krebs cycle occur?

Mitochondrial matrix

How much energy from one glucose does one turn of the Krebs cycle yield? When we combine with with our products for glycolysis, how many in total?

One turn yields 30 ATP

-- +2 form glycolysis = 32 ATP TOTAL

What does one turn of Krebs cycle yield? (4) How much ATP is each of this worth?

1) 3 NADH

-- 2.5 ATP each

2) 1 FADH2

-- 1.5 ATP each

3) 1 GTP

-- 1 ATP each

4) 2 CO2

What is the transition/Hubb reaction/prep step from glycolysis to the Kreb's cycle? What is the enzyme? What is used/released to accomplish this?

Pyruvate --> Acetyl CoA

Enzyme: Pyruvate Dehydrogenase

Uses: NAD+

Release: NADH + CO2

Why can fats not be converted to carbohydrates, but both fatty acids and pyruvate can be converted to Acetyl CoA?

Pyruvate --> Acetyl CoA is an IRREVERSIBLE reaction (pyruvate dehydrogenase)

This is why fat cannot be converted from FA to Acetyl CoA back up to Pyruvate

-- Hubb reaction/Preparation Step

What 5 coenzymes does the prep/transition step require?

1) Thiamine pyrophosphate (vit B1)

2) FAD (B2)

3) CoA (B5)

4) Lipoic Acid

5) NAD (B3)

These Five Coenzymes Love Nutrition

To convert FAs to Acetyl CoA, what is the acronym for reactions used?

OHOT

What is step 1 of the Kreb's cycle? What is the enzyme?

Acetyl-CoA --> Citrate

Enzyme: Citrate synthase

What is step 2 of the Kreb's cycle? What is the enzyme?

Citrate --> Isocitrate

Enzyme: Aconitase

What is step 3 of the Kreb's cycle? What is the enzyme?

Isocitrate --> a-ketoglutarate

Enzyme: Isocitrate Dehydrogenase

What is step 4 of the Kreb's cycle? What is the enzyme?

a-ketoglutarate --> Succinyl-CoA

Enzyme: a-ketoglutarate Dehydrogenase

What is step 5 of the Kreb's cycle? What is the enzyme?

Succinyl-CoA --> Succinate

Enzyme: Succinate Synthase

What is step 6 of the Kreb's cycle? What is the enzyme?

Succinate --> Fumarate

Enzyme: Succinate Dehydrogenase

What is step 7 of the Kreb's cycle? What is the enzyme?

Fumarate --> Malate

Enzyme: Fumarase

What is step 8 of the Kreb's cycle? What is the enzyme?

Malate --> Oxaloacetate

Enzyme: Malate Dehydrogenase

What steps of the Kreb's cycle use Dehydrogenase enzymes?

Steps 3, 4, 6, & 8

How does the Kreb's cycle restart?

Oxaloacetate combines with Acetyl-CoA to make Citrate

What are the 3 enzyme regulating inhibitors of the Kreb's cycle?

1) ATP (high energy charge)

2) NADH or FADH2

3) High NADH/NAD ratio

What are the 3 enzyme regulating stimulants of the Kreb's cycle?

1) AMP or ADP

2) NAD+ or FAD+

3) Low NADH/NAD ratio

What steps of the Kreb's cycle will use NAD+, producing NADH? What step of the Kreb's cycle will use FAD, producing FADH2?

Step 3 -- (Isocitrate dehydrogenase)

Step 4 -- (a-ketoglutarate dehydrogenase)

Step 8 -- (malate dehydrogenase)

Step 6 -- (Succinate dehydrogenase)

NOTE ALL the dehydrogenase enzymes in the Kreb's cycle either use NAD+ or FAD

When using glucose in the Kreb's cycle, how many turns can be done? When using a fatty acid, such as Palmitate (16:0), how many turns can be done?

Glucose = 2 turns

Fatty Acid = 1 turn for every 2 carbons

-- Palmitate (16:0) = 8 turns

What is the electron transport chain?

Is a sequence of electron carrier molecules that shuttle electrons, down a series of reactions that release energy; used to make ATP.

Where is the electron transport chain located?

Inner mitochondrial membrane (cristae)

What are the 4 complexes of the ETC?

Complex 1 = NADH Dehydrogenase

Complex 2 = Succinate Dehydrogenase

Complex 3 = Cytochrome bc1 comples

Complex 4 = Cytochrome c oxidase

Which Complexes of the ETC are a proton pump? How many H+ are produced?

Complex 1 = 4 H+

Complex 3 = 4 H+

Complex 4 = 2 H+

Complex 2 is the ONLY one not a proton pump

What is the best electron acceptor for the ETC?

Oxygen

What are the 4 steps of Complex I for ETC?

1) NADH --> NAD+ passes electrons to FMN

2) e- passed to FMNH2

3) e- passed to Fe-S

4) e- passed to ubiquinone (CoQ)

PROTON PUMP

What are the 4 steps of Complex II for ETC?

1) Succinate --> Fumarate produces FAD

2) FAD passes e- to FADH2

3) e- pass to Fe-S

4) e- pass to ubiquinone (CoQ)

NOT a proton pump (No energy is lost)

What is Coenzyme Q (Ubiquinone)?

Mobile electron carrier accepting electrons form Fe-S (complex I & II)

-- carries electrons to Complex III

NOTE: NOT a protein

What are the 3 steps of Complex III for ETC?

1) Accepts e- from CoQ

2) e- passed from cytochrome b to Fe-S to cytochrome c1

3) e- passed to cytochrome c

PROTON PUMP

For a proton pump, the H+ are pumped from ________ to __________.

Inner mitochondrial membrane to intermembrane space

What are the 3 steps of Complex IV of the ETC?

1) Accepts electrons from cytochrome c

2) e- are passed to Cu-A --> cytochrome a --> Cu-B --> cytochrome a3

3) Then passed to OXYGEN (final electron acceptor; produces 2 water or you can say 1/2 O2 = 1 H2O)

PROTON PUMP

T/F: As we go down the ETC, the most positive redox pairs are at the start (complex 1 & 2) and the most negative redox pairs are near the end (Complex 4 & water/O2).

FALSE

The most negative redox pairs at start

The most positive redox pairs at end

What is an aldehyde or ketone with multiple hydroxyl groups?

Carbohydrate

Where is the OH in an alpha carbohydrate? Beta carbohydrate?

alpha = OH below ring

-- fish swim

beta = OH above ring

-- birds fly

What type of bond is between carbohydrate rings?

alpha 1-4 bond

L & D are used for the configuration of the asymmetric carbon farthest from the aldehyde or keto group? Where do we see the OH with L? D?

L = OH on Left

D = OH on right

What sugar combination is maltose? Lactose? Sucrose?

What are the bonds with each of these?

Maltose = glucose + glucose (a 1-4)

Lactose = galactose + glucose (B 1-4)

Sucrose = glucose + fructose (a 1-2)

What are the bonds seen in Dextrin? Amylose & Amylopectin (Starch)? Glycogen? Cellulose?

Dextrin = a 1-4 & a 1-6

Starch:

Amylose = a 1-4

Amylopectin = a 1-4 & a 1-6

Glycogen = a 1-4 & a 1-6

Cellulose = B 1-4

-- CANNOT BE DIGESTED

What is the main enzyme for glycogen synthesis that has an active (a) and inactive (b) form? What bonds does it create?

Glycogen synthase

a 1-4 bonds

What enzyme starts the process of glycogen synthesis? What enzyme drives it forward?

Glycogen Initiator Synthase

Pyrophosphatase

What enzyme of glycogen synthesis makes the branches?

Glucosyl 4:6 Trasnferase

What 3 things stimulate glycogen synthase?

1) Insulin

2) Glu 6P

3) ATP

NOTE: high energy state

-- almost completely opposite of GNG (Liver ADP/AMP instead of ATP)

What is the main enzyme for glycogen breakdown with an active (a) and inactive (b) form? What bonds does this break?

Glycogen Phosphorylase

breaks (a 1-4) bond

NOTE: Glycogen phosphorylase is OPPOSITE of glycogen synthase

What enzyme of glycogen breakdown breaks bonds close to the branch? Which enzyme breaks the branches (a 1-6)?

Glucosyl 4:4 Transferase

Amylo a (1-6) Glucosidase

What are the 4 stimulants of glycogen breakdown?

1) Glucagon

2) Catecholamines (epi and norepi)

3) Calcium (muscle)

4) AMP and ADP

NOTE: Low energy state

What is the delta carbon in a fat? The omega carbon? The alpha carbon? The beta carbon?

w = first carbon (CH3)

Delta = last carbon (COOH)

a = carbon before last carbon (delta)

B = two carbons before last carbon (delta; one before alpha C)

CH3-CH2-CH2-CH2-COOH

(w) (B) (a) (delta)

What is oxidation of a fat at the B carbon?

B-oxidation

What enzyme adds a double bond at a number of carbons from the "delta" carbon?

Delta desaturases

What is cis vs trans?

Cis = larger functional groups are on SAME side of double bond

Trans = larger functional groups are on OPPOSITE sides of double bond

What is the omega name for Linoleic acid?

18:2w6

What is the omega name for Linolenic acid?

18:3w3

What is the omega name for Arachidonic Acid?

20:4w6

What is the omega name for Eicosapentaenoic Acid (EPA)?

20:5w3

What is the omega name for Docosahexaenoic Acid (DHA)?

22:6w3

What is the omega name for Palmitic Acid?

16:0

What is the omega name for Stearic acid?

18:0

What is the omega name for Oleic Acid?

18:1w9

What 4 things stimulate Fat synthesis?

1) Insulin

2) ATP

3) Glucose

4) Citrate

NOTE: High energy state

Overflow of what molecule from the Krebs cycle can lead to fat synthesis? What enzyme is used to convert this to break this down into OAA + Acetyl CoA?

Citrate

Citrate lyase

What is the first step of Fat synthesis? What enzyme is used? What other molecules are used?

Acetyl CoA + CO2 --> Malonyl CoA

Enzyme = Acetyl CoA Carboxylase (ACC)

Use = ATP

What is the second step of Fat synthesis? What enzyme is used? What other molecules are used?

Growing FA + Malonyl CoA --> FA + 2 more C's

Enzyme = Fatty Acid Synthase (FAS)

Used = NADPH

What is the acronym of reactions that occurs with fat synthesis while fatty acid synthase (FAS) keeps adding malonyl CoAs to the growing fatty acid chain?

CRDR

Condensation

Reduction

Dehydration

Reduction

Fatty acid synthesis continues at step 2 until it reaches what end product?

Palmitate (C16)

What enzyme is used to go from a saturated fatty acid to an unsaturated fatty acid?

Desaturase

What enzyme is used to increase a FA chain by 2 carbons (FA --> FA + 2C)

Elongase

What 3 things stimulate Fat mobilization?

1) Glucagon

2) Catecholamines

3) AMP & ADP

NOTE: Low energy state

What enzymes take TAG --> Free FAs in the adipocyte? How about in the muscle?

Hormone sensitive Lipase (HSL)

-- HSLm = Hormone sensitive Lipase of the Muscle

FA + CoA + ATP --> ???

- Why is this equation/product important?

Acyl-CoA

-- can enter the mitochondria!

What transports FAs into the mitochondria? What is the enzyme that transports FAs into the mitochondria?

Carnitine

CPT (carnitine palmitoyl transferase)

Where does fat metabolism occur?

Matrix of mitochondria

What is the first reactant of fat metabolism? What is the end product and where can it go once created?

Acyl CoA

Acetyl CoA

- (Krebs Cycle)