Carbohydrates Flashcards

Question

What is the product of a _glucose_ and _galactose_ molecules linked by a glycosidic bond? What kind of glycosidic bond?

Answer 1

**Lactose** is 1 glucose and 1 galactose molecule linked by a **β(1→4) glycosidic bond**.

Answer 2

**Sucrose** is 1 glucose and 1 fructose molecule linked by a **α1→β2 glycosidic bond.**

Answer 3

**Lactase** or **Sucrase deficiency.**

Answer 4

**Oligosaccharides** are condensation products of 3-10 monosaccharides. Ex. _Maltotriose_

Answer 5

**Polysaccharides** are condensation products of \>10 monosaccharide units. Ex. *_Starch_**,* *_Glycogen_**,* *_Inulin_**,* *_Cellulose_**,* *_Chitin_*

Answer 6

False. Most oligosaccharides are **_NOT_** digested by human enzymes. Others can be only partially digested by humans.

Answer 7

The undigested portion serves as food for the intestinal microflora. Depending on the type of oligosaccharide, different bacterial groups are stimulated or suppressed. The Sialyl-Lewis x Oligosaccharide is the most abundant carbohydrate receptor present in the outer coating (zona pellucida) of the human ova, and is implicated as a large factor of Sperm-ZP binding leading to fertilization.

Answer 8

**STARCH** is a homopolymer of glucose forming an α-glycosidic chain called **glucan** or **glucosan**.

Answer 9

**GLYCOGEN** is the storage polysaccharide in animals, sometimes called ANIMAL STARCH.

Answer 10

**Inulin** a polysaccharide of fructose used to determine GFR.

Answer 11

Glycogen forms chains of 12-14 **α-D-glucopyranose residues** in a **α1→4 glucosidic linkage** with branching through a **α1→6 glucosidic bond.**

Answer 12

Glycogen forms chains of 12-14 α-D-glucopyranose residues in a **α1→4 glucosidic linkage**.

Answer 13

Glycogen forms branching through a **α1→6 glucosidic bond.**

Answer 14

**Cellulose** is the chief constituent of plant cell walls.

Answer 15

Cellulose is consists of **β-D-glucopyranose units** linked by **β1→4** bonds to form long straight chains strengthened by cross-linking hydrogen bonds. It is **insoluble** and *cannot be digested by mammals*.

Answer 16

Mammals only possess **α-glucosidases** that cleave α-glucosidic linkages hence dietary fibers cannot be digested and are passed in stool (ex. kangkong, corn)

Answer 17

**Chitin** is the structural polysaccharide in the exoskeleton of crustaceans and insects.

Answer 18

Inulin is used to determine **GFR**.

Answer 19

**Glycosaminoglycans** are complex carbohydrates containing **amino sugars** and **uronic acids**. ## Footnote *Ex. hyaluronic acid, chondroitin sulfate, heparin*

Answer 20

**Proteoglycans** are glycosaminoglycans attached to a protein molecule

Answer 21

Glycosaminoglycans were formerly known as **mucopolysaccharides**

Answer 22

Glycoproteins were formerly known as **mucoproteins**

Answer 23

**Glycoproteins** are proteins containing branched or unbranched oligosaccharide chains.

Answer 24

Isomers are compounds that have the **same chemical formula** but **different structures**.

Answer 25

Epimers are compounds that differ in configuration around one **one specific carbon atom** (*except the carbonyl carbon*)

Answer 26

α-D-glucose & **α-D-galactose** are epimers at **C4**. α-D-glucose & **α-D-mannose** are epimers at **C2**.

Answer 27

α-D-glucose & α-D-galactose are epimers at **_C4_**.

Answer 28

α-D-glucose & α-D-mannose are epimers at **_C2_**.

Answer 29

Enantiomers are pairs of structures that are **mirror images** of each other.

Answer 30

**Levo-rotatory** (left-handed) and **Dextro-rotatory** (right-handed)

Answer 31

**D-glucose**

Answer 32

**α-D-glucose** & **α-D-galactose** are epimers at C4

Answer 33

**α-D-glucose** & **α-D-mannose** are epimers at C2.

Answer 34

Anomers are sugars that are **convertible between linear and ring form**.

Answer 35

**Cyclic** or **ring forms** are more common anomers.

Answer 36

The ring form results in the *formation of the anomeric carbon*.

Answer 37

Anomers are designated as **α** and **β configurations** of the sugar.

Answer 38

**Mutarotation** is the process wherein α and β forms spontaneously interconvert in a solution. In a solution, α and β forms are in **EQUILIBRIUM**.

Answer 39

A furan ring is a **5 carbon** ring.

Answer 40

A pyran ring is a 6 carbon ring.

Answer 41

The principle sites of carbohydrate digestion are the **mouth** and **intestinal lumen**.

Answer 42

Digestion of carbohydrates are generally completed by time the food reaches the **junction of the duodenum and jejunum**.

Answer 43

Carbohydrate digestion begins during **mastication in the mouth**. Physical digestion = _mastication_ Chemical digestion = _salivary amylase_

Answer 44

Pancreatic amylase hydrolyses **complex carbohydrates** to **disaccharides** and **trisaccharides** but *not directly to monosaccharides.*

Answer 45

**Disaccharidases** in the **brush border** complete the digestive process. ## Footnote *Ex. isomaltase, maltase, lactase, sucraase*

Answer 46

Amylase can only digest **α(1→4) glycosidic bonds**.

Answer 47

**GLUT-5** transports _glucose_, _galactose_, and _fructose_ from the lumen into the cell via *facilitated diffusion*. "GLUT-5 = LUMEN has 5 letters"

Answer 48

**GLUT-2** transports _ALL sugars_ from the cell into the blood via *facilitated diffusion*. "GLUT-2 = BM has 2 letters"

Answer 49

**SGLT-1 (Sodium Glucose LUMINAL Transporter-1)** transports _glucose_ and _galactose_ ONLY from the lumen into the cell via *secondary active transport*. SGLT-1 is a Na-hexose symporter.

Answer 50

**Fructose**

Answer 51

**Glucose** and **Galactose**

Answer 52

**GLUT-5** and **SGLT-1**

Answer 53

**GLUT-2 **is found on the basement membrane of the intestinal epithelium

Answer 54

SGLT-1 is a **Na-hexose symporter** therefore in order to enhance the absorption of sodium it must be transported with glucose. *ORS-75 has equal moles of Na and glucose (75 mEq/l sodium, 75 mmol/l glucose)*

Answer 55

The **Glycemic Index** is increase of blood glucose after a test dose of a carbohydrate compared with that after an equivalent amount of glucose.

Answer 56

The **Gylcemic Index** will tell you how fast a carbohydrate is absorbed.

Answer 57

A carbohydrate with a glycemic index **\> 1** has a **fast absorption**.

Answer 58

A carbohydrate with a glycemic index **\< 1** has a **slow absorption**.

Answer 59

Food with **LOW** glycemic index is beneficial to DM and dieting * prevents rapid rises in blood glucose * prevents rapid fluctuations in insulin secretion

Answer 60

Acquired enzyme deficiency occurs during **severe diarrhea** because the enzymes are removed in stool. Advise patients with AGE to *avoid dairy products*.

Answer 61

**Metabolism** is the sum of all the chemical reactions in a cell, tissue, or the whole body.

Answer 62

**Anabolic pathways** or **Anabolism** yields synthesis of compounds from smaller raw materials hence it is _endergonic_ and _divergent_. ## Footnote *Ex. protein & triglyceride synthesis, glycogenesis*

Answer 63

**Catabolic pathways** or **Catabolism** results in the breakdown of larger molecules hence it is _exergonic_ and _convergent_. ## Footnote *Ex. glycolysis, beta-oxidation, glycogenolysis*

Answer 64

Catabolism produces **reducing equivalents** and **ATP** (mainly via the respiratory chain) usually through oxidative reactions.

Answer 65

**Amphibolic pathways** is the link between anabolic and catabolic pathways. ## Footnote *Ex. TCA (Kreb's) cycle*

Answer 66

**Regulators of Metabolism** 1. Signals within the cell 2. communication between cells 3. second messenger systems

Answer 67

* substrate availability * product inhibition * allosteric activators or inhibitors

Answer 68

* through direct contact via gap junctions * through synaptic signalling via NT * through endocrine signalling via hormones

Answer 69

* Calcium/inositol triphosphate (IP3): *epinephrine* * Adenylyl cyclase system (cAMP): *glucagon, epinephrine* * Guanylate cyclase system (cGMP): *ANP, NO*

Answer 70

**Adenylyl cyclase system**

Answer 71

**Adenylate cyclase**

Answer 72

**cAMP phosphodiesterase** degrades cAMP

Answer 73

**Gs** stimulates adenylate cyclase hence **decreases cAMP**

Answer 74

**Gi** inhibits adenylate cyclase hence **increases cAMP**

Answer 75

**GLUT 1 & 3** are found in the brain and placenta ## Footnote *"1 and 3 put side by side looks like a B (remember P almost looks like i too)"*

Answer 76

**GLUT 1, 2 & 3** are found in the kidney ## Footnote *"**K**indergarden kid(ney)s learn **1,2,3"***

Answer 77

**GLUT-4** requires insulin for the uptake of glucose therefore will be found in tissue *where it can be stored* such as **SKELETAL & CARDIAC MUSCLE** and **ADIPOSE**.

Answer 78

**GLUT-5** is found in the **luminal side of the small intestines** and absorbs glucose into the body

Answer 79

**GLUT-2** does not require insulin therefore will be found in *tissues that need to detect glucose levels* such as the **LIVER**, **PANCREATIC B-CELL** *(as a stimulus to release insulin)*, **KIDNEY**, and **SMALL INTESTINE**

Answer 80

Skeletal muscles, cardiac muscles and adipose store glucose (or its derivatives) therefore they possess **GLUT-4** which *requires insulin for the uptake of glucose.*

Answer 81

**_High-yield GLUT_** Brain = **GLUT 1 & 3** *(looks like B)* Insulin-stimulated = **GLUT-4** *(storage so in muscle and fat)* Insulin-independent = **GLUT-2** *(level detector so in pancreas, liver, kidney, SI)* Glucose absorption = **GLUT-5** *(lumen of SI so for absorption)*

Answer 82

It is the major pathway for glucose metabolism that converts glucose into 3-carbon compounds to provide energy

Answer 83

Glycolysis occurs in the **CYTOPLASM** of **ALL cells**

Answer 84

Substrate = **glucose** Products = **2 pyruvate** (aerobic) or **2 lactate** (anaerobic)

Answer 85

Aerobic glycolysis is dependent on: * presence of mitochondria * availability of oxygen

Answer 86

**P**hospho**F**ructo**K**inase-**1** (PFK-1) in **G**lyco**L**ysis *"**P**apa **F**ranz **K**issed **1** girl → **G**e**L**a"*

Answer 87

**Energy Investment** - energy is used up to produce phosphorylated intermediates *(2 ATP is consumed)* **Energy Generation** - ATP is produced through substrate-level phosphorylation *(4 ATP and 2 NADH generated)*

Answer 88

The 3 _irreversible_ and _regulated_ steps in glycolysis are: **Step 1:** phosphorylation of glucose **Step 3:** phosphorylation of fructose-6-phosphate **Step 10:** formation of pyruvate

Answer 89

**Hexokinase** & **Glucokinase**

Answer 90

**Hexokinase:** present in _most tissues_ **Glucokinase:** only in _liver_ and _islet cells of the pancreas_

Answer 91

**Hexokinase:** inhibited by _G-6-P_ **Glucokinase:** inhibited by _F-6-P_

Answer 92

**Hexokinase:** low Km so high affinity *(used by all cells even in fasting/low sugar levels)* **Glucokinase:** high Km so low affinity *(removes only the glucose in excess and converts it to storage form)*

Answer 93

**Hexokinase:** _low Vmax_ so it is *easily saturated* then *acts at a constant rate to provide only what* *the cell's needs* **Glucokinase:** _high Vmax_ so *helps remove the glucose that is in excess of the cell's needs* * "Glucokinase = eating at vikings"* * "Hexokinase = eating skyflakes"*

Answer 94

**Hexokinase** has a _low Km_ and _high affinity_ for glucose so it can be used by all cells even in fasting/low sugar levels. It has a _low Vmax_ so it is easily saturated when blood glucose levels are high then acts at a constant rate to provide G-6-P for the cell's needs. **Glucokinase** has _high Km_ and _low affinity_ so it is active in high blood glucose levels (following a meal) to remove only the excess and convert it to G-6-P to be stored hence it is only found in the *liver* and *pancreas*. It has a _high Vmax_ so it is not saturated at high glucose levels. * "Glucokinase = eating at vikings* * Hexokinase = eating skyflakes"*

Answer 95

**Hexokinase** & **Glucokinase** catalyses the phosphorylation of *glucose to G-6-P*.

Answer 96

**Phosphofructokinase-1** catalyzes phosphorylation of *F6P to F-1,6-BP* ## Footnote *\*\*\*rate-limiting step of glycolysis*

Answer 97

**Pyruvate kinase** catalyses the phosphorylation of *phosphoenolpyruvate (PEP) to pyruvate*

Answer 98

**PFK-1** converts F-6-P to F-**_1_**,6-P * activated by F-2,6-BP and AMP * inhibited by ATP and citrate **PFK-2** converts F-6-P to F-**_2_**,6-P * activated by the well-fed state, increased insulin and decreased glucagon * inhibited by reverse of its activators.

Answer 99

Pyruvate kinase is activated by **F-1,6-BP** (feedforward mechanism)

Answer 100

**increased glucagon** and **cAMP**

Answer 101

_**AT**P generating:_ **P**hospho**G**lycer**ATE** **K**inase **P**yruvate **K**inase *"**_AT_**e,* ***P**akibukas ang **GATE** **K**apag* ***P**apasok si **K**uya"*

Answer 102

_**NA**DH generating:_ **G**lyceralde**HYDE**-**3**-**P**hosphate **D**ehydrogenase "**_NA_**nay, **G**o and **HIDE** sa **TREE** **P**akipot kay **D**addy"

Answer 103

_**AT**P generating_: *"**_AT_**e, **P**akibukas ang **GATE** **K**apag **P**apasok si **K**uya"* * **P**hospho**G**lycer**ATE** **K**inase * **P**yruvate **K**inase _**NA**DH generating_: * "**_NA_**nay, **G**o and **HIDE** sa **TREE** **P**akipot kay **D**addy"* * **G**lyceralde**HYDE**-**3**-**P**hosphate **D**ehydrogenase

Answer 104

1 molecule of glucose will yield **4 ATP** molecules via substrate level phosphorylation.

Answer 105

**_Fates of Pyruvate_** 1. converted to LACTATE by *lactate dehydrogenase* in *anaerobic glycolysis* 2. converted to ACETYL-CoA by *pyruvate dehydrogenase* in the *citric acid cycle* 3. converted to OXALOACETATE by *pyruvate carboxylase* in *gluconeogenesis* 4. converted to ETHANOL by *pyruvate decarboxylase* in *fermentation* (yeast)

Answer 106

In **aerobic glycolysis**, pyruvate enters the **citric acid cycle** however there must be *sufficient mitochondria* and *available oxygen*. _Lack thereof_ will preferentially convert pyruvate to **lactate** in **anaerobic glycolysis**.

Answer 107

NADH proceeds to the **Electron Transport Chain.**

Answer 108

NADH and FADH transported into the inner mitochondrial membrane via the * **Malate-Aspartate Shuttle**: 1 NADH = 3 ATP * **Glycerol-Phosphate Shuttle: **1 NADH = 2 ATP

Answer 109

The final product of the Glycerol-Phosphate Shuttle is **FADH₂** will enter the TCA cycle in _Complex II_ hence only 2 ATP are produced as opposed to the Malate-Aspartate Shuttle that produces **ATP** which binds to _Complex I_ to produce 3 ATP.

Answer 110

Mitochondria

Answer 111

**INNER** mitochondrial membrane

Answer 112

Pyruvate is reduced to **Lactate** by **Pyruvate Dehydrogenase** using **1 NADH**.

Answer 113

**R**BC, **L**ens, **C**ornea, **K**idney **M**edulla, **Testes**, **W**BC *"**R**e**L**i **C**an **K**ick **M**y **BALLS** until its **WHITE** (when someone kicks you in the balls you can't breathe so _anaerobic_"*

Answer 114

**2,3-bisphosphoglycerate mutase** bypasses phosphoglycerate kinase in RBCs to produce 2,3-BPG from 1,3-BPG.

Answer 115

In conditions with **low oxygen** (ex. living in high altitudes) increased levels of 2,3-BPG be found

Answer 116

**Arsenic poisoning** * inhibits _pyruvate dehydrogenase_ by binding to *lipoid acid* * competes for *inorganic phosphate* as a substrate for _glyceraldehyde-3-P-D_

Answer 117

Treat arsenic poisoning with **chelation** with *dimercaprol* or *succimer*

Answer 118

**Arsenic poisoning** * inhibits pyruvate dehydrogenase by binding to lipoid acid * competes for inorganic phosphate as a substrate for glyceraldehyde-3-P-D Treat with chelation with dimercaprol or succimer

Answer 119

**Pyruvate Kinase Deficiency** * most common enzyme defect in glycolysis * 2nd MC enzyme deficiency causing _hemolytic anemia_

Answer 120

Pyruvate Kinase Deficiency *lacks ATP* which impairs the *Na-K-ATPase pump* without which intracellular gradient cannot be maintained and *cell swelling* and *lysis* will ensue.

Answer 121

The most common cause of intravascular haemolytic anemia is **G6PD deficiency** which has ***heinz bodies*** in the peripheral smear and a ***precipitating history of oxidative stress*** or "trigger" (PK deficiency is the 2nd MC and lacks the said characteristics)

Answer 122

The most common trigger is **infection** (other causes: drugs, fava beans)

Answer 123

**Muscle Phosphofructokinase Deficiency**

Answer 124

**Pyruvate dehydrogenase complex**

Answer 125

1. **Thiamine pyrophosphate** (Vit B1) 2. **Lipoid acid** 3. **Coenzyme A** (contains Vit B5: pantothenic acid) 4. **FAD** (from Vit B2: riboflavin) 5. **NAD⁺** (from Vit B3: niacin) *"**T**ender **L**oving **C**are **F**or **N**ix"*

Answer 126

1. **T**hiamine pyrophosphate (Vit B1) 2. **L**ipoid acid 3. **C**oenzyme A (contains Vit B5: pantothenic acid) 4. **F**AD (from Vit B2: riboflavin) 5. **N**AD+ (from Vit B3: niacin) "**T**ender **L**oving **C**are **F**or **N**ix"

Answer 127

ENZYMES 1. **P**yruvate **D**ehydrogenase 2. **α**-**K**eto**G**lutarate **D**ehydrogenase COFACTORS 1. **T**hiamine pyrophosphate (Vit B1) 2. **L**ipoid acid 3. **C**oenzyme A (contains Vit B5: pantothenic acid) 4. **F**AD (from Vit B2: riboflavin) 5. **N**AD+ (from Vit B3: niacin) "**P**agka **D**epressed, **A**lejandrino **K**uyas **G**ive **D'** **T**ender **L**oving **C**are **F**or **N**ixor"

Answer 128

Pyruvate is converted to **Acetyl-CoA** and will also produce **NADH** and **CO₂**.

Answer 129

**Pyruvate Dehydrogenase Deficiency** is the most common biochemical cause of congenital lactic acidosis and is inherited as an **X-linked dominant** condition.

Answer 130

**Pyruvate Dehydrogenase Deficiency** leads to deprivation of Acetyl-CoA in the brain leading to psychomotor reiteration and death. It is treated with a **ketogenic diet**.

Answer 131

**Chronic alcoholism** is an acquired pyruvate dehydrogenase deficiency. It leads to ***fatal pyruvic and lactic acidosis***. *_Thiamine_* (Vit B1) is deficient.

Answer 132

* TriCarboxylic Acid Pathway * Kreb's Cycle (eponym) * Citric Acid Cycle

Answer 133

**TCA cycle** is amphibolic * provides majority of the ATP for energy * gluconeogenesis from skeletons of amino acids (malate) * building blocks for amino acids and heme (succinyl CoA) * fatty acid synthesis (citrate)

Answer 134

The TCA occurs in **ALL cells with a mitochondria**. It occurs in the **mitochondrial matrix** *except for _succinate dehydrogenase_* which is located in the *_inner mitochondrial membrane._*

Answer 135

substrate = **Acetyl Co-A** products = **NADH, FADH2, GTP** and **CO₂**

Answer 136

*"**C**indy **I**s **K**inky **S**o **S**he **F**ornicates **M**ost **O**ften"*

Answer 137

Because **two acetyl-CoA** molecules are produced from each glucose molecule, _two cycles_ are required per glucose molecule. Therefore, at the end of two cycles, the products are: **2 ATP, 6 NADH₂, 2 FADH₂, 2 QH₂ (ubiquinol)** and **4 CO₂**.

Answer 138

**_TCA_**: **I**so**C**itrate **D**ehydrogenase *"**_T_**e**_CA_**, **I** **C**ee **D**isappointment"*

Answer 139

**Citrate** delivers acetyl CoA to the cytoplasm for fatty acid synthesis via a **_citrate shuttle_**.

Answer 140

Succinyl CoA

Answer 141

**Succinyl CoA** and **glycine** make up **D-ALA** for a precursor for **_heme synthesis_**.

Answer 142

NONE, there is no hormonal control for the TCA cycle.

Answer 143

NONE, the cycle does not synthesize NEW oxaloacetate.

Answer 144

**12 ATPs** are produced per 1 mole of acetyl CoA

Answer 145

**15 ATPs** are produced per 1 mole of pyruvate. Converting pyruvate to acetyl CoA will *yield 1 additional NADH* hence *3 ATPs via ETC* (no shuttle because already in the mitochondria).

Answer 146

**3 NADH** and **2 CO₂**

Answer 147

**4 NADH** and **3 CO₂**

Answer 148

**Isocitrate→ αKG →succinyl CoA** by the enzymes **ICD** and **αKGD** respectively ## Footnote * \*\*\*these rxns also yield **NADH*** * \*\*\*\*also **pyruvate→acetyl CoA** catalysed by **PD** (the step before entering TCA)*

Answer 149

**Isocitrate→ αKG →succinyl CoA** by the enzymes **ICD** and **αKGD** respectively as well as **malate→OAA** catalysed by **MD** ## Footnote *\*\*\*these rxns also yield CO₂*

Answer 150

**Succinate→Fumarate** catalysed by **SD**

Answer 151

**Succinyl CoA→Succinate** catalysed by **STK** reduces GDP to GTP

Answer 152

Gluconeogenesis is for the production of glucose from the ff intermediates: * intermediates of glycolysis and TCA * glycerol from TAGs * lactate from the Cori Cycle * carbon skeletons (α-ketoacids) of glycogenic amino acids

Answer 153

Gluconeogenesis occurs in the **liver (90%)** and **kidneys (10%)**. It occurs in BOTH the **mitochondria** and **cytoplasm**.

Answer 154

***"HUG"*** 1. **H**eme synthesis 2. **U**rea cycle 3. **G**luconeogenesis

Answer 155

Kidneys contributed as much as **40%** (from 10%)

Answer 156

The substrate of gluconeogenesis is **pyruvate** and its product is **glucose**.

Answer 157

**F**ructose **1**, 6 (**S**Ix) **B**is**P**hosphate in **G**luco**N**eogenesis *"**F**ranz **1**s **S**Ingle - **B**asta **P**uro **G**V **N**a"*

Answer 158

In the Cori Cycle, the lactate generated during anaerobic metabolism is brought to the liver where it is converted to glucose by hepatic gluconeogenesis then brought back to the muscles and RBC.

Answer 159

The Cori Cycle utilises **4 ATP**s.

Answer 160

**_3 irreversible steps in gluconeogenesis_**** ***(reverse of glycolysis)*: **Step 10:** pyruvate → OAA → PEP **Step 3:** dephosphorylation of F-1,6-BP to F-6-P **Step 1:** dephosphorylation of G-6-P to glucose

Answer 161

Step 10 has 2 reactions that reverse Pyruvate Kinase: 1. pyruvate → OAA is catalysed by ***pyruvate carboxylase*** which requires **biotin** and **ATP** 2. OAA → PEP is catalysed by ***PEP carboxykinase*** which requires **GTP**.

Answer 162

GTP is mostly produced in the **β-oxidation of fats** hence patients with deficient fat metabolisms have problems in gluconeogenesis.

Answer 163

**_Carboxylases:_** 1. **pyruvate carboxylase** (gluconeogenesis) 2. **acetyl CoA carboxylase** (fatty acid synthesis) 3. **propionyl CoA carboxylase** (β-oxidation of fatty acids with odd # of carbons)

Answer 164

Carboxylases require **BIOTIN** as a co-factor.

Answer 165

Step 3 reverses **PFK-1**: F-1,6-BP → F-6-P is catalysed by ***fructose-1,6-bisphosphatase*** * activated by **ATP** * inhibited by **F-2,6-P** and **AMP**

Answer 166

* promotes glycolysis by activating **PFK-1** * inhibits gluconeogensis by inhibiting **F-1,6-BPase**

Answer 167

Step 1 reverses **hexokinase** & **glucokinase**: G-6-P → glucose is catalysed by **G-6-Pase**.

Answer 168

**Gluconeogenesis** and **glycogenolysis** share the final step, G-6-P → glucose.

Answer 169

G-6-P is converted to glucose by G-6-Pase in the **liver** and **kidneys** _only_. Muscle lacks this enzyme hence G6P cannot be transported across the cell membrane without being dephosphorylated. Therefore, glycogen stored within it can only be utilized by muscle.

Answer 170

**_Regulation of Gluconeogenesis _** * circulating levels of glucagon * viability of glycogenic substances * allosteric activation by acetyl CoA * allosteric inhibition by AMP

Answer 171

gluconeogenesis uses **4 ATP**, **2 GTP** and oxidises **2 NADH** back to NAD+

Answer 172

If blood glucose concentration **exceeds 9.5-10 mmol/L (300mg/dL)**, glycosuria occurs. **Glucosuria** is when the glomerular filtrate contains more glucose than can reabsorbed hence will appear in urine.

Answer 173

In alcoholism, high amounts of NADH is formed by *alcohol dehydrogenase* and *acetaldehyde dehydrogenase.* **High amounts of NADH** favors the ff rxns: * pyruvate → lactate * OAA → malate * DHAP → glycerol-3-P

Answer 174

1. high fetal consumption and hyperinsulinemia (due to high estrogen) causes **fasting hypoglycemia** 2. elevated HPL causes insulin resistance hence **postprandial hyperglycemia**

Answer 175

* LBW and premature babies have **little adipose tissues.** * enzymes of gluconeogenesis of neonates are **not yet completely functional**

Answer 176

**α(1→4) glycosidic bonds** for elongation

Answer 177

**α(1→6) glycosidic bonds** for branching

Answer 178

**Liver** (100g = 6%) and **muscle** (400g = \<1%) _ONLY_

Answer 179

Glycogen is a branched polymer of glucose used for storage of carbohydrates in animals.

Answer 180

Muscle glycogen **lacks G6Pase.**

Answer 181

Glycogenesis synthesizes new glycogen molecules from α-D-glucose for storage of carbohydrates

Answer 182

Glycogenesis occurs in the **liver** and **muscle**. It occurs in the **cytosol**.

Answer 183

SUBSTRATES = **UDP-glucose**, **ATP**, **UTP** and **glycogenin** (the core primer protein) PRODUCT = **glycogen**

Answer 184

The rate-limiting step of glycogenesis is the **elongation of glycogen** through the *addition of α(1→4) glycosidic bonds* by **glycogen synthase**.

Answer 185

**Important steps in glycogenesis** 1. **G6P→G1P** catalysed by *phosphoglucomutase* 2. **synthesis of UDP-glucose** by *UDP-glucose phosphorylase* 3. **elongation of glycogen chains** by *glycogen synthase* 4. **formation of branches** in glycogen by the *branching enzyme*

Answer 186

**Glycogen synthase** elongates glycogen chains through the *addition of α(1→4) glycosidic bonds at the non-reducing end (carbon 4) of glucose residues.*

Answer 187

**Branching enzyme** forms branches in glycogen through the *addition of new α(1→6) glycosidic bonds* and *transferring 5-8 glucosyl residues*

Answer 188

**glucose-1-P** and **UTP**

Answer 189

Glycogenolysis shortens glycogen chains to produce molecules of α-D-glucose

Answer 190

Glycogenolysis occurs in **liver** and **muscle**. Its occurs in the **cytosol**.

Answer 191

SUBSTRATE = **glycogen** PRODUCTS = **G-1-P** and **free glucose** (produced during the debranching process)

Answer 192

The liver can release free glucose to the circulation while the muscle is limited to G-6-P which will be confined in the muscle solely for its own use.

Answer 193

The rate-limiting step in glycogenolysis is the **removal of glucose by the breaking α(1→4) bonds** by ***glycogen phosphorylase***

Answer 194

**debranching enzyme** α(1→4)→α(1→4) glucantransferase transfers the limit dextrin **amylo-α(1→6) glucosidase** removes a free glucose by breaking the α(1→6) bond PRODUCTS: **free glucose** from the breakage of the α(1→6) bond

Answer 195

**phosphoglucomutase** catalyses the reaction G1P→G6P. This is the *final step in glycogenolysis in the muscle* while the liver further converts G6P to glucose through the enzyme G-6-Pase.

Answer 196

**α(1→4) glucosidase** or **acid maltase** degrades lysosomal glycogen and its deficiency leads to lysosomal accumulation of glycogen (**Pompe's disease** or **GSD type II**)

Answer 197

**GLYCOGEN STORAGE DISEASES** are a group of inherited disorders characterised by deposition of abnormal type or quantity of glycogen in tissues. There are **12 types** total, all of which are enzyme deficiencies.

Answer 198

**GSD type I : Von Gierke's Disease **is characterised by hepatomegaly, renal enlargement, hypoglycemia, lactic acidosis/ketosis

Answer 199

**_GSD type I : Von Gierke's Disease_** is deficient in **G-6-Pase**, lack of which *inhibits final steps of glycogenolysis and gluconeogenesis* and leads to accumulation. This results in ***severe hypoglycemia***. Phosphorylated glucose cannot leave the hepatocyte and kidney (***hepatic & renal enlargement***) so an increase in glycolytic pathway metabolites occurs and are metabolized into lactate (***lactic acidosis***). Glucose is also shunted into making more triglycerides, causing an increase in LDL and VLDL which will lead to β-oxidation → ketogenesis → ***ketosis***.

Answer 200

**_GSD type III : Forbes-Cori's Disease_** manifests as hepatomegaly, splenomegaly, progressive weakness, muscle wasting of interossei. Its manifestations are a **milder form of GSD type I** but unlike GSD I, *kidney enlargement is _not_ observed*.

Answer 201

**_GSD type III : Forbes-Cori's Disease_** is deficient in **debranching enzyme** which causes the body to form glycogen molecules that have an abnormal structure. Its manifestations are **hepatomegaly**, **splenomegaly**, **progressive weakness**, and **muscle wasting of interossei**. Its manifestations are a milder form of GSD type I but unlike GSD I, *kidney enlargement is not observed.*

Answer 202

_**GSD type IV : Andersen's Disease** or_ **_Amylopectinosis_** is characterised by hepatic failure, cirrhosis, hepatosplenomegaly, cardiomyopathy, failure to thrive, hypotonia, and ventricular arrhythmias. Its manifestations are a **severe form of GSD type I.**

Answer 203

_**GSD type IV : Andersen's Disease** or **Amylopectinosis**_ is deficient in **branching enzyme** leading to a cytoplasmic accumulation of dextrin (unbranched glycogen). Deficiency relates to **liver disease** and include hepatic failure, cirrhosis, hepatosplenomegaly, **cardiomyopathy** (less frequent), **failure to thrive**, **hypotonia** and **ventricular arrhythmias**. Its manifestations are a severe form of GSD type I.

Answer 204

**_GSD type II : Pompe's Disease_** is characterised by cardiomegaly, heart failure, macroglossia, asymmetry of affected muscle groups, and limb-girdle weakness. *Respiratory muscle involvement and cardiomegaly is a hallmark of Pompe's disease*.

Answer 205

**_GSD type II : Pompe's Disease_** is deficient in **acid maltase** which results in accumulation of structurally normal glycogen in lysosomes which may interrupt normal functioning of other organelles. It is characterised by heart failure, macroglossia, asymmetry of affected muscle groups and limb-girdle weakness. ***Respiratory muscle involvement** and **cardiomegaly** is a hallmark of Pompe's disease.*

Answer 206

**_GSD type V : McArdle's Disease_** is characterised by cramps, fatigue, exercise intolerance, progressive proximal weakness, "second-wind" phenomenon and myoglobinuria without lactic acidosis

Answer 207

**_GSD type V : McArdle's Disease_** is deficient in **skeletal muscle glycogen phosphorylase**. With intense exercise, glucose from glycogen stores in muscle becomes the predominant resource and fatigue develops when the glycogen supply is exhausted hence it is characterised by cramps, fatigue, pain after exercise, progressive proximal weakness, and **"second-wind" phenomenon**. ***Myoglobinuria _without_ lactic acidosis*** may result from the breakdown of skeletal muscle known as rhabdomyolysis (often provoked by a bout of exercise). In the long term, patients may exhibit renal failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.*Hypoglycemia is _not_ an expected finding because liver phosphorylase is not involved.*

Answer 208

**_GSD type V : McArdle's Disease_** may exhibit a “second wind” phenomenon, characterized by better tolerance for aerobic exercise after approximately 10 minutes.If a patient nearing fatigue slows exercise to a tolerable level, a point exists at which exercise may be increased again without previous symptoms. This is attributed to the *combination of increased recruitment of motor units, increased cardiac output & blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins.*

Answer 209

**_Dissacharide lactose_** in milk is an important source of galactose.

Answer 210

Lactose = **glucose** + **galactose** (milk and dairy products) hydrolysed by ***lactase*** in the ***intestinal brush border***

Answer 211

**False**. Only disaccharidases and trisaccharidases can.

Answer 212

**Hexokinase** has a greater affinity for glucose (**lower Km**)

Answer 213

**_Important steps in Galactose Metabolism_** 1. **Phosphorylation of galactose to galactose-1-P** by ***galactokinase*** and ***hexokinase*** 2. **Formation of UDP-galactose** from Gal-1-P and UDP-glucose by ***Gal-1-P uridyl transferase*** 3. **Use of galactose as a carbon source** by converting UDP-galactose to UDP-glucose by the enzymes ***UDP-hexose-4-epimerase***

Answer 214

**Galactokinase deficiency** causes cataracts in early childhood, galactosemia and galactosuria

Answer 215

**Classic Galactosemia** is the absence of ***Gal-1-P uridyl transferase*** where galactitol accumulates and causes cataracts within a few days of birth, hypoglycemia, galactosemia, galactosuria, hepatosplenomegaly, hypotonia and mental retardation.

Answer 216

**_Absolute contraindications for breastfeeding_** * Infants with Classic Galactosemia * Mothers who use illegal drugs * Mothers infected with HIV, HTLV, active herpes lesion on the breast * Mothers taking any of the following medications: *radioactive isotopes, chemotherapy, and thyrotoxic agents.*

Answer 217

Both have *galactosemia and galactosuria* and are managed by *eliminating galactose from diet* but **Classic Galactosemia (Gal-1-P uridyl transferase deficiency)** causes _cataracts within a few days of birth_ while **galactokinase deficiency** causes _cataracts later on in early childhood_. Classic Galactosemia is also associated with hypoglycemia, hepatosplenomegaly, hypotonia and mental retardation.

Answer 218

Disaccharidases and trisaccharidases are located in the **intestinal brush border**.

Answer 219

**Dissacharide sucrose** in **honey** and **fruits** is an important source of fructose.

Answer 220

Sucrose = **glucose + fructose** (honey and fruits) hydrolysed by ***sucrase*** in the ***intestinal brush border***

Answer 221

**Fructose** has the fastest metabolism and greatest yield of energy

Answer 222

**_Important steps in fructose metabolism_** 1. Phosphorylation of fructose to F-1-P by *hexokinase* or *fructokinase* 2. Formation of DHAP and glyceraldehyde from F-1-P by *aldolase B*

Answer 223

**Aldolase A** is used in _glycolysis_ and uses _F-1,**6-B**P_ as a substrate while **Aldolase B** is used in _fructose metabolism_ and uses _F-1-P_ as a substrate.

Answer 224

**Essential Fructosuria** is a defect in *_fructokinase_* and is benign and asymptomatic whose only sign is the *_appearance of fructose in blood and urine_*.

Answer 225

**Fructose Intolerance** is a deficiency of *_Aldolase B_* which manifests as *hypoglycaemia, jaundice, cirrhosis, and vomiting*. Patient is treated by *eliminating of fructose and sucrose from diet.*

Answer 226

**_Essential Fructosuria_** is a defect in ***fructokinase*** and is benign and asymptomatic whose only sign is the appearance of fructose in blood and urine. **_Fructose Intolerance_** is a deficiency of ***Aldolase B*** which manifests as hypoglycemia, lactic acidosis, jaundice, cirrhosis, and vomiting. Patient is treated by eliminating of fructose and sucrose from diet.

Answer 227

**Galactitol** accumulates and causes cataracts within a few days of birth

Answer 228

Glycoproteins

Answer 229

**Mannose-6-P → Fructose-6-P** in catalyzed by ***phosphomannose isomerase***

Answer 230

***Aldolase reductase*** catalyses **glucose → sorbitol** and is found in *RBCs, lens, retina, schwann cells, liver, kidney, placenta, ovaries, and seminal vesicles.*

Answer 231

***Sorbitol dehydrogenase*** catalyses **sorbitol → fructose** and is found only in the *seminal vesicles.*

Answer 232

In **DM**, there is so much glucose that equilibrium favors the formation of sorbitol. Sorbitol cannot cross cell membranes and the lens and nerves lack sorbitol dehydrogenase which leads to intracellular accumulation of sorbitol produces *_osmotic stresses_* on cells by drawing water into the insulin-independent tissues. Hydropic lens fibers degenerate and form cataracts. Neuropathy affects all peripheral nerves including pain fibers, motor neurons and the autonomic nervous system.

Answer 233

In the **sorbitol-aldose reductase pathway** or **polyol pathway**, unused glucose is reduced to sorbitol by ***aldose reductase*** then ***sorbitol dehydrogenase*** can oxidize sorbitol to fructose. Fructose can return to the glycolysis pathway through the action of ***hexokinase***. The polyol pathway appears to be *_implicated in diabetic complications_*, especially in microvascular damage to the retina, kidney, and nerves.

Answer 234

_**Pentose Phosphate Pathway** or **Hexose Monophosphate Pathway (HMP shunt)**_ produces important intermediates: * produces NADPH which provides electrons for 1. FA & steroid biosynthesis 2. reduction of glutathione 3. cytochrome P450 4. WBC respiratory burst 5. Nitric Oxide synthesis * Produces ribose-5-P used for synthesis of nucleotides * Metabolic use of 5-carbon sugars

Answer 235

The pentose phosphate pathway * **_ACTIVE_** in the ***liver, adipose, adrenals, thyroid, testes, RBC, lactating mammaries*** * **_LOW_** in ***skeletal muscles*** and ***non-lactating mammaries***. It occurs in the **cytoplasm** of the cell. *\*\*\*active in tissues that produce lipids because NADPH is important in lipid synthesis*

Answer 236

_Pentose phosphate pathway_ substrate = **G-6-P** products = **R-5-P, F-6-P, glyceraldehyde-3-P** along with **NADPH** *\*\*\*No ATP is consumed or produced*

Answer 237

**_Phase 1 : Oxidative Phase_** key enzyme: ***G6PD*** main products: ***NADPH, R5P*** **_Phase 2 : Non-Oxidative Phase_** key enzyme: ***transketolases*** main products: ***R5P, F6P, glyceraldehyde-3-P***

Answer 238

**RBC transketolase activity** can be used to diagnose thiamine deficiency since thiamine is a *necessary co-factor of transketolases*. Apart from the baseline enzyme activity (which may be normal even in deficiency states), *acceleration of enzyme activity after the addition of thiamine pyrophosphate* may be diagnostic of thiamine deficiency

Answer 239

**False.** Transketolases is a class of enzymes collectively termed so.

Answer 240

**False.** Transketolase catalyzes reactions that are _reversible_ and _NOT_ rate-limiting.

Answer 241

**Ribose-5-phosphate** is the most important product of the non-oxidative of the PPP and is used for the *synthesis of nucleotides*.

Answer 242

Reduced glutathione (G-SH) sequesters harmful H2O2 in a reaction catalysed by ***glutathione peroxidase*** with ***selenium*** as a co-factor. Oxidized glutathione (GSSG) is returned to its reduced form by ***glutathione reductase*** and consumes ***1 NADPH*** in the process. ## Footnote *\*\*\*only reduced glutathione can remove H2O2*

Answer 243

The glutathione peroxidase/reductase pathway is important in **RBC**s.

Answer 244

**G6PD deficiency** involves ↓ NADPH in RBCs and ↓ activity of glutathione reductase causing free radicals and peroxides to accumulate. **Hemolytic anemia** ensues due to poor RBC defense against oxidizing agents.

Answer 245

The precipitating factors of hemolytic anemia are anything that can cause oxidative stress 1. **infection** - most common 2. **drugs**: **_A_**nti-biotics (sulphonamides, chloramphenicol), **_A_**nti-malarials (primaquine), **_A_**nti-pyretics *(except ASA and paracetamol)* 3. **fava beans**

Answer 246

**neonatal jaundice** 1-4 days after birth peripheral smear: **heinz bodies** & **bite cells**

Answer 247

*Altered hemoglobin precipitates* within RBCs and form **heinz bodies** and the presence of which will cause the *phagcytic removal by the spleen* forming **bite cells**

Answer 248

chronic granulomatous disease is deficient in ***NADPH oxidase*** which converts oxygen to superoxide in leukocytes (esp neutrophils and MØ ) which are used in the respiratory burst that kills bacteria.

Answer 249

**_Catalase-positive bacteria_****:** * All species of Staphylococcus * Family Enterobacteriaceae (*Citrobacter, E.Coli, Enterobacter, Klebsiella, shigella, yersinia, proteus, salmonella, serratia*) * Listeria * Fungi: Candida & Apergillus *"**C**ata**LASE** **SPYKES** **P**rote**C**ts **Staph**, not strep" * ***_C_**andida, **_L_**isteria, **_A_**spergillus, **_S_**erratia, **_E_**. Coli* ***_S_**almonella, **_P_**seudomonas, **_Y_**esinia, **_K_**lebsiella**, _E_**nterobacter,** _S_**higella* ***_P_**roteus, **_C_**itrobacter, **_Staph_**ylococcus*