Biochemistry II Flashcards

1
Q

What is biotransformation?

A

Metabolic process to facilitate the excretion of endogenous and exogenous substances (mainly occurs in the liver) by altering their chemical structure

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2
Q

What types of substances are excreted by biotransformation (2)?

A

endogenous and exogenous substances

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3
Q

How many phases are possible in the biotransformation?

A

Phase 1, 2 and 3

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4
Q

What can happen to the substances by catalytic enzymes (3)?

A

substance inactive, active or toxic

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5
Q

Where does a majority of biotransformation occur? What are some other sources of this processes (6)?

A

Majority of biotransformation occurs in the hepatocytes but also extrahepatic sources such as adipose, intestine, kidney, lung, placenta, and skin

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6
Q

What effects biotransformation (6)?

A

Affected by age, gender, nutritional status, disease state, meds and genetics

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7
Q

What does phase 1 yield?

A

Yield a polar, H2O soluble metabolite that is still active

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8
Q

What happens to many of the substrates after phase 1?

A

Many become the substrates for Phase 2 reactions

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9
Q

What are redox reactions?

A

Oxidation-Reduction
Redox reactions require that electrons be transferred or removed to either reduce or oxidize a particular substrate or molecule

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10
Q

What happens to electrons during oxidation?

A

electron loss (May manifest in an increased in ionic charge)

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11
Q

What happens to electrons during reduction?

A

is election gain

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12
Q

When an atom is _________ in a reaction, it loses electrons to another atom.

A

oxidized

the oxidized atom/compound is a reducing agent/reductant

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13
Q

Atoms that gain electrons are _________.

A

Reduced, it is an oxidizing agent/oxidant

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14
Q

Fe + 2 HCL yields FeCl2 + H2

What is being oxidized or is the reducing agent?

A

Fe

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15
Q

Fe + 2 HCL yields FeCl2 + H2

What is being reduced or is the oxidizing agent?

A

HCl

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16
Q

What is oxidation?

A

usually manifests as increasing bonds to oxygen or decreasing bonds to hydrogen (electron transfer versus dehydrogenation

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17
Q

What type of reactions do oxidation produce?

A

Exothermic reaction

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18
Q

What are the different examples of oxidation in the body?

A
  • Cytochrome P450 monooxygenase system (P450, CYP 450)
  • Flavin-containing monooxygenase system
  • Monoamine oxidase (MOA)
  • Alcohol and aldehyde dehydrogenase
  • Peroxidases
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19
Q

What is reduction?

A

Opposite of oxidation

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20
Q

What is the major oxidating system in the body?

A

Cytochrome P450 monooxygenase system (P450, CYP 450)

  • diverse system with ~57 isoforms)
  • Prone to many interactions (can be induced or inhibited)
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21
Q

What is involved in the reduction process?

A

P 450 microsomal system involved

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22
Q

What state does reduction usually occur?

A

More prone to occur in anaerobic states

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23
Q

When is reduction usually seen?

A

Seen with decreased bonding with oxygen or increased bonding with hydrogen

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24
Q

What are two substrates present in all organisms? Why are they are important?

A

Nicotinamide adenine dinucleotide (NAD+/NADH) along with its phosphorylated form (NADP+/NADPH) are two molecules present in all organisms. Factors in catabolic and anabolic processes.

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25
Q

What is hydride H+?

A

coenzyme as a carrier: the anion of H

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26
Q

What are the NADH/NAPH?

A

reduced forms

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27
Q

What is happening in the following molecule?

Drug + O2 + H+ + NADPH ➡️ Drug-OH + H2O + NADP+

A
NADPH used  (not ATP)
Splitting of oxygen molecule
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28
Q

Where does hydrolysis occur? What does it not involve?

A

Usually occur outside the liver (does not involve P450 enzyme system)

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29
Q

What doe esters enzymes usually react with?

A

ester bond of compounds (and amides)

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30
Q

What is used in the process of hydrolysis?

A

H2O is used in the process (can be substitution, elimination, solvation reactions)

-These agents tend to be shorter acting than their counterparts

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31
Q

What process is important in the digestion of saccharides, proteins and fat?

A

Hydrolysis

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32
Q

What is the opposite reaction of hydrolysis?

A

condensation (some esters are formed by condensation of alcohol and carboxylic acid- would be subject to hydrolysis)

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33
Q

What is an example of condensation?

A

ester local anesthetics

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34
Q

Where are hydrolytic enzymes most commonly found (4)?

A

plasma, RBCs, GI, synaptic clefts

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35
Q

What are some other examples of hydrolytic enzymes?

A

Proteases, lipase, Phosphatase & Esterases

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36
Q

What are drug examples in hydrolysis (6)?

A

esmolol, ester local anesthetics, remifentanil, acetylcholine, succinylcholine, ASA

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37
Q

What does phase 2 yield (2)?

A
  • large polar metabolite by adding a hydrophilic group to form a H2O soluble, inactive compound that can be readily excreted
  • Synthetic reactions
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38
Q

What is an important component of conjugation?

A

Most common form of congugation: Conjugation with glucuronic acid involves the P450 (synthesized from glucose and added to a lipid-soluble drug to render H2O soluble)

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39
Q

What is the hallmark of phase 2?

A

Conjugation

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40
Q

What are glucuronide conjugates excreted in?

A

bile/urine (example: bilirubin, steroid/thyroid hormones)

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41
Q

What is flood’s opinion of conjugation?

A

Flood considers a Phase 1 reaction since a 1-step process as becomes hydrophilic and does not need further biotransformation (ONLY conjugation that uses microsomal enzymes) (Nagelhout: Phase 2)

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42
Q

What is the goal of conjugation?

A

render a lipid soluble agent polar/H2O soluble for elimination (drug may undergo Phase 1 then further transformation via Phase 2)

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43
Q

What are the types of enzymes in the conjugation?

A

Numerous enzymes: -transferases

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44
Q

What are some examples of agents that only goes through Phase 2 (3)?

A

if agent already has a functional group): Propofol, morphine, midazolam`

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45
Q

What can conjugation and p450 have on some agents?

A

render some agents into active metabolites with their own metabolic profile

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46
Q

What does phase 1 refer to?

A

Phase 1 refers to redox and hydrolysis reactions to render a substance more polar for excretion of placing carboxy or hydroxy groups to prepare for phase 2 (adding a functional structure)

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47
Q

Where does the P450 enzyme system occur?

A

endoplasmic reticulum of hepatocytes and mitochondria

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48
Q

What is the site of action of hydrolysis?

A

sites of action via hepatic/extrahepatic cellular enzymes, plasma; type of enzymes vary

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49
Q

What does phase 2 refer to?

A

Phase 2 involves coupling a compound or its metabolite to another compound

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50
Q

What are examples of phase 2 (5)?

A

glucuronidation, methylation, acetylation, sulfation, or conjugation with glutathione or certain amino acids (glycine, taurine, glutamic acid

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51
Q

Where does phase 2 occur (4)?

A

Occurs in the cytosol, membranes, mitochondria, ER

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52
Q

What is a synthetic reactions?

A

new compound created

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53
Q

When does phase 3 occur?

A

post-phase 2 (chemical substance undergoes further metabolism and excretion

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54
Q

What occurs during phase 3?

A

Xenobiotic transporters in the liver (think bile excretion), kidneys, and small intestines removexenobiotics(toxins, antigens) and metabolites from cells

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55
Q

What type of process is phase 3?

A

Antiporter/Efflux porter systems (active process)

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56
Q

What are some examples of phase 3 (3)?

A

ATP-binding cassette (ABC), Solute carrier (SLC) transporters and P-glycoprotein

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57
Q

What is important the components of the mitochondria layer?

A

There is an inner layer and outer layer of the mitochondria

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58
Q

What are carbs broken down into?

A

simplest forms (glucose, galactose, fructose)

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59
Q

What is galactose and fructose are converted to? What changes glucose enter into the cell?

A

Glucose-6-phosphate in the liver (glucokinase changes glucose entering any cell into the same)

Glucokinase

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60
Q

What does galactokinase convert?

A

Galactose phosphorylated (think energy) to galactose-1-phosphate

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61
Q

What is the ultimate produce of glucose breakdown? Which enzyme is involved?

A

further enzymatic processes is glucose-6-phosphate or glycogen by way of glucose-1- phosphate

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62
Q

What is Glucose-6-PHOSPHATE? What liberates it?

A

glucose within the cell- “trapped.” Must be liberated by glucose phosphatase to enter bloodstream in its free form (liver to bloodstream to other cells)

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63
Q

What is fructose phosphorylated?

A

has own catabolic pathway

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64
Q

What step does fructose phosphorylated enter into the kerb cycle?

A

enters glycolysis as a glyceraldehyde late in the sequence right before pyruvate is generated (or makes glycogen)

65
Q

What is the process of fructose phosphorylated?

A

fructose-1-phosphate by fructokinase

66
Q

What does insulin facilitate?

A

rapid entry of free-form glucose into the cells

67
Q

What are other ways glucose enters the cell (3)?

A

enters by facilitated/passive diffusion (concentration gradient via GLUT), active Na+/glucose co-transport (SGLT), active transport via ATP

68
Q

What are the four step process for cellular respiration (glucose to energy)?

A

-Glycolysis
-Pyruvate dehydrogenase (pyruvate oxidation)
-Kreb’s Cycle
-Oxidative phosphorylation (electron transport)
via NAD/NADH+ and FAD/FADH2

69
Q

What is NADH? How many ATP does it yield?

A

nicotinamide adenine dinucleotide (NADH), a coenzyme derived from vitamin B3 or niacin (net 3 ATP)

70
Q

What is FADH2? How many ATP does it yield?

A

flavin adenine dinucleotide (FADH2), a coenzyme derived from Vitamin B2 or riboflavin (net 2 ATP)

71
Q

What are the forms that NADH/FADH exist?

A

-can exist in the reduced form or oxidized form: NADH/FADH2 – reduced form (“loaded”) and NAD+ & FAD+

72
Q

What is the importance of NAD+ & FAD+?

A

Both participate in oxidation and reduction reactions and help in the transfer of electrons from one substrate to the other.

73
Q

Can be synthesized in the body?

A

Yes

74
Q

What do NAD+ & FAD+ take part in?

A

Both molecules take part in metabolic pathways which include carbohydrate, fatty acid, amino acid and nucleotide metabolism

75
Q

What is the pre Kreb cycle?

A

Glycolysis

76
Q

What happens to glucose during glycolysis?

A

A 6-carbon sugar—undergoes a series of chemical transformations.

77
Q

What is the end byproduct from glycolysis?

A

2 individual pyruvate molecules, a 3-carbon organic molecule

78
Q

How many ATP is made during glycolysis?

A

2 ATP

79
Q

How many nadh is made during glycolysis?

A

2 NADH

80
Q

What is produced from glycolysis?

A

ATP is made andNAD+ is converted (REDUCED) to NADH

81
Q

What forms glycogen?

A

Glucose-6-phosphate converted to Glucose-1-phosphate to form glycogen or enters metabolic pathway

82
Q

What is the limiting process of glycolysis?

A

Phosphofructokinase (PFK)

Enzyme for fructose-6-phosphate to fructose-1,6 bisphophate

83
Q

What is Phosphofructokinase (PFK)?

A

The reaction by PFK is thermodynamically favorable and practically irreversible

84
Q

What is fermentation?

A

is the process of glycolysis in anaerobic conditions- limits the oxygenation available to oxidize NAD. Pyruvate becomes the driver

85
Q

What is a negative byproduct of glycolysis in anerobic conditions?

A

Lactate acid (it is transported to liver and converted to glucose)

86
Q

What is the total ATP created during Glycolysis? How many is actually yielded?

A

4 ATP; 2 ATP

87
Q

What is another pre Kreb’s cycle?

A

Pyruvate Oxidation

88
Q

What happens to pyruvate oxidation?

A

EACH pyruvate from glycolysis goes into the mitochondrial matrix—the innermost compartment of mitochondria.

89
Q

What happens to pyruvate once it enters the mitochondrial? What is it it bounded too?

A

There, pyruvate is oxidized via NAD+ to a 2- carbon molecule (an acetyl group) that is bound to Coenzyme A

90
Q

What is generated from pyruvate oxidation?

A

One pyruvate= 1 CO2 (is generated as the carboxyl group is released) and 1 NADH

Total from one glucose is 2 CO2 and 2 NADH

91
Q

What is the byproduct of pyruvate oxidation?

A

Acetyl-CoA

92
Q

What does Acetyl-CoA interact with during the kreb’s cycle? What does it form?

A

reacts with oxaloacetate forming citrate to enter a series of enzymatic

93
Q

What is yielded from the Kreb’s cycle?

A

From one pyruvate= 2-CO2- 3 NADH, 1 FADH, and 1 ATP

From 2 pyruvate or one glucose molecule= 4-CO2- 6 NADH, 2 FADH, and 2 ATP

94
Q

What is the end product of the kreb cycle?

A

Oxaloacetate

95
Q

Each pyruvate molecule goes through a _______ process (original glucose molecule generates 2 pyruvates)

A

Kreb cycle process

96
Q

What happens when you break down a carbon?

A

One less carbon and CO2 is formed

97
Q

What is important about CoEnzyme A (COA)?

A

Role in the synthesis and oxidation of fatty acids and oxidation of pyruvate in the citric acid cycle (versatile metabolic enzyme)

98
Q

What is CoEnzyme A (COA) synthesized from?

A

Naturally synthesized frompantothenate(vitamin B5)

99
Q

What forms Acetyl CoA?

A

Pyruvate is oxidized to and combined with CoEnzyme A (Pyruvic acid is an alpha keto acid- carboxylic acid compound)

100
Q

Why is CoEnzyme A (COA) important for in the Kreb’s cycle?

A

In its acetyl form: Provides an acetyl group for reaction in the Kreb’s cycle

  • Acetyl group : methyl group single-bonded to carbonyl
  • There is an acryl-CoEnzyme
101
Q

What is an acetyl group?

A

methyl group single-bonded to carbonyl

102
Q

What are the end results NADH, FADH2, GTP or ATP, CO2 from 1 pyruvate?

A

3-NADH, 1 FADH2, 1 GTP OR ATP, 2 CO2

103
Q

What are the end results NADH, FADH2, GTP or ATP, CO2 from 2 pyruvate or 1 glucose?

A

6-NADH, 2 FADH2, 2 GTP OR ATP, 4 CO2

104
Q

What is oxidative phosphorylation?

A

Oxidation of high-energy electron carriers NADH and FADH2 are passed along a chain of membrane-based enzymatic reactions (Electron-Transport Chain)

105
Q

What stage do you get most ATP development?

A

Electron Transport Chain

106
Q

What happens to energy released from oxidative phosphorylation?

A

Used to pump protons out of the mitochondria inner (the electrons that are conveyed by NADH/FADH2 do the work to move the protons)

107
Q

Where does the electron transport chain occur?

A

mitochondria inner

108
Q

What happens to hydride during the electron transport chain?

A

must lose 2 electrons to become a proton H+

109
Q

What is created from the movement of protons across the membrane by the electron transport chain?

A

creates acharge differential to synthesize ATP (ATP synthase)

110
Q

What is ATP production dependent on?

A

(proportional) on the proton gradient (the energy)- more negative charge in the inner membrane, protons drive ATP production

111
Q

What causes the protons in the inner membrane?

A

sourced through the chemical reactions in each phase of glucose metabolism: Free and tied to NADH (H+ carrier)

112
Q

What is the final electron acceptor in the electron transport chain?

A

oxygen, to ultimately form water (H20).

113
Q

What is the oxygen reduced to form?

A

Water (H2O)

114
Q

What is the only part of the glucose metabolism that uses atomospheric oxygen?

A

final electron acceptor in the chain is oxygen, to ultimately form water. Atmospheric oxygen can move freely across the cell membrane

115
Q

What is also being produced by the electron transport chain?

A

ATP

116
Q

Where is ADP and ATP imported from?

A

The mitochondrial ADP/ATP carrier imports ADP from the cytosol and exports ATP from the mitochondrial matrix

117
Q

What is Coenzyme Q?

A

ubiquinone: one of the transporters of protons across the mitochondrial membrane

118
Q

Why impact does ATP have on the citric acid cycle?

A

Negative feedback-Regulator inhibitor enzyme

119
Q

Why impact does ADP, AMP have on the citric acid cycle?

A

Positive feedback- Regulator activates enzyme

120
Q

Glycolysis and gluconeogenesis serve ______- role

A

opposing

121
Q

What are inhibitor enzymes of phosphofructokinase (PFK)?

A

ATP, citrate

122
Q

What are activator enzymes of phosphofructokinase (PFK)?

A

AMP

123
Q

What is another name of anaerobic metabolism?

A

Fermentation

124
Q

What is important relationship of oxygen and glycolysis?

A

In the glycolysis stage (glucose breakdown to pyruvate does NOT require oxygen, albeit inefficient and low yield of energy

125
Q

How many kilocalories for a glucose molecule?

A

24K calories (3%)

126
Q

How is lactic acid formed?

A

formed from pyruvic acid with NADH)- some amount is always being made- diffuses into extracellular fluid and transported to liver.

127
Q

When does lactic acid become a problem?

A

when it accumulates (acidosis and not sustainable source of energy

128
Q

What is the formation of lactic acid known as?

A

Cori Cycle

129
Q

Once _______ is restored, lactic acid restored to glucose in the liver

A

oxygen

130
Q

What are two other fuel sources besides glucose?

A

Fatty acids and proteins

131
Q

What are triglycerides hydrolyzed into?

A

into fatty acids and glycerol- transported to tissues

132
Q

Where aren’t triglycerides hydrolyzes?

A

brain and RBC’s

133
Q

What is the process of beta oxidation (Fatty acids as fuel?

A

Degradation and oxidation to form Acetyl CoA to enter Kreb’s cycle with oxaloacetic acid

134
Q

Where does beta oxidation?

A

Mitochondria

135
Q

Glycerol also used in the _______ pathway

A

glycolytic

136
Q

Fatty acids are polymers of ______

A

acetic acid

137
Q

What forms acetoacetic acid?

A

In the liver Acetyl CoA

138
Q

What is the byproduct of acetoacetic acid?

A

β-hydroxybutyric acid and acetone

139
Q

What are ketoacidosis? Does this utilize glucose?

A

Ketoacidosis that results when accumulates in times of starvation (low carbohydrates source)- derived because you can not utilize glucose

140
Q

What is the storage of lipids?

A

In contrast to glycogen, large amounts of lipids can be stored for energy (primary source when glucose not available). Higher ratio of C-O’s

141
Q

Epinephrine and norepinephrine activate ______________

A

Lipase

142
Q

What is the energy proceed from fatty acids in comparison of glucose?

A

Tremendous source of energy (150 x more than glucose (glycerol binds 14-18 carbon chains to make fatty acids)

143
Q

What happens to excess Acetyl CoA?

A

produced by carbohydrates is formed into fatty acids in the cytosol (Acetyl CoA carboxylase)

144
Q

Synthesis of fatty acids occurs _______ than degradation!

A

faster

145
Q

What happens to excess carbohydrate consumption?

A

acts a fat-sparer (insulin) but converted to fat

146
Q

What happens to excess amino acids?

A

excess are deaminated (oxidative process) to alpha keto acids + glutamic acid

147
Q

What happens have amino acids are deaminated (2)?

A

Enter the Kreb’s cycle (produces less ATP than glucose), or released into bloodstream and picked up by adipocytes and converted to fat

148
Q

What is ammonia converted to?

A

Ammonia resulting from the deamination process is converted to urea in the liver for excretion via kidneys

149
Q

What is a byproduct of amino acid deaminated?

A

Ammonia

150
Q

What happens to some amino acids?

A

Some amino acids break down to similar products that result from glucose or lipid metabolism

151
Q

What are some amino acid that have importance in the kreb cycle?

A

alanine, cysteine, serine, glycine

152
Q

What is deaminate alanine?

A

pyruvic acid

153
Q

What is ketogensis?

A

Can be converted to glucose, glycogen or Acetyl CoA, which is polymerized to fatty acids

154
Q

What is a ketone body?

A

2 molecules of Acetyl-CoA can condense to form acetoacetic acid

155
Q

What spares protein metabolism?

A

Proteins are spared by carbohydrate and lipid metabolism - problem with starvation

156
Q

What happens to amino acids in the absence of proteins?

A

body degrades 20-30 g/day of proteins for amino acids

157
Q

What promotes protein synthesis (4)?

A

Growth hormone, insulin, testosterone, thyroid

158
Q

What is glucocorticoids?

A

promote gluconeogenesis and the breakdown of fat and proteins for fuel