Biochem - Metabolism

Question 1

Which pathway (Glycolysis or Gluconeogenesis) are more active if there is:

a. High levels of Fructose-1,6-Biphosphate

b. Low levels of Fructose-1,6-Biphosphate

Answer 1

a. Glycolysis
b. Gluconeogenese

Question 2

Pyruvate Dehydrogenase Complex Deficiency

1. How does it present?
2. Why?

Answer 2

1. • Lactic Acidosis

- Neurologic defects

- increased serum alanine

2. Since there is no pyruvate dehydrogenase, pyruvate will not be able to be converted into acetyl-coA and enter the TCA cycle so instead, this buildup of pyruvate will be shunted into the lactic acid and alanine pathways of pyruvate

Question 3

What is the treatment for Pyruvate Dehydrogenase complex deficiency and why does it work?

Answer 3

Increased intake of ketogenic nutrients (lysine and leucine)

Metabolism of ketogenic amino acids (lysine and leucine) can provide energy in the form of acetyl-coA without increasing lactate production

Question 4

What are the 4 possible fates of pyruvate?

Answer 4

1. Acetyl-CoA (TCA cycle)
2. Oxaloacetate (Gluconeogenesis)
3. Alanine
4. Lactate (anerobic glycolysis)

Question 5

Pyruvate —-> Alanine

What enzyme is responsible?

What cofactors are required?

Answer 5

Alanine Aminotransferase

cofactor: B6

Question 6

Pyruvate —-> Oxaloacetate

What enzyme is responsible?

What cofactors are required?

Answer 6

Pyruvate Carboxylase

cofactor: Biotin (B7)

Question 7

Pyruvate —-> Acetyl-CoA

What enzyme is responsible?

What cofactors are required?

Answer 7

Pyruvate Dehydrogenase

cofactor: B1, B2, B3, B5, lipoic acid

Question 8

Pyruvate —-> Lactate

What enzyme is responsible?

What cofactors are required?

Answer 8

Lactic Acid Dehydrogenase

cofactor: B3

Question 9

Lactate Dehydrogenase Deficiency

1. How does it typically present?
2. Why?

Answer 9

1.

Exercise intolerance

(Muscle fatigure, pain, cramps with exercise)

2.

They cannot produce lactate and therefore lack anaerobic glycolysis

(LDH is needed to regenerate NAD+)

Question 10

Pyruvate Kinase Deficiency

1. How does it present?
2. Why?

Answer 10

Hemolytic anemia with splenomegaly

Pyruvate Kinase converts Phosphoenylpyruvate into Pyruvate while generating 1 ATP in the process.

RBC’s dont have a mitochondria so they heavily rely on this enzyme for energy.

Question 11

alpha ketoglutarate dehydrogenase

1. What reaction does it catalyze?
2. What cofactors does it require?

Answer 11

1.

alpha-ketoglutarate —-> Succinyl-CoA

2.

B₁, B₂, B₃, B₅, Lipoic acid

(same as pyruvate dehydrogenase)

Question 12

Which reaction in the Krebs cycle generates GTP?

What is it needed for?

Answer 12

Succinyl-CoA —–> Succinate

GTP is required by Phosphoenylpyruvate Carboxykinase (oxaloacetate –> phoesphoenylpyruvate) in gluconeogenesis

Question 13

What reaction in the Krebs cycle generates FADH₂?

What cofactor is needed for this reaction?

Answer 13

Succinate —(succinate dehydrogenase)—> Fumarate

Cofactor: B2 (riboflavin)

Question 14

What are the 2 reactions of the HMP shunt?

Answer 14

1. Glucose-6-Phosphate

—(Glucose-6-phosphate dehydrogenase)—>

6-phosphogluconolactone

2. Ribulose-5-Phosphate

—–(transketolase + B1 cofactor)—->

Fructose-6-Phosphate

Question 15

What is the main function of the HMP shunt?

Answer 15

To make NADPH for:

• glutathione reduction inside RBCs

- Fatty acid synthesis

- cholesterol synthesis

Note: it also make some ribulose for nucleotide synthesis

Question 16

Essential Fructosuria

1. Deficient/defective enzyme
2. Symptoms

Answer 16

1. Fructokinase
2. Asymptomatic

(other than fructose in urine)

Question 17

Why is essential fructosuria asymptomatic?

Answer 17

Since Hexokinase will take over for fructokinase and convert Fructose into Fructose-1-Phosphate

Question 18

Hereditary Fructose Intolerance

1. Deficient Enzyme
2. Symptoms

Answer 18

1. Aldolase B

(converts Fructose-1-P into either DHAP or Glyceraldehyde)

2. Hypoglycemia, Jaundice, Cirrhosis, Vomitting

Question 19

Why does Hereditary Fructose Intolerance result in hypoglycemia?

Answer 19

Since there is deficient aldolase B, there will be an accumulation of Fructose-1-Phosphate

Phosphate will become less available and gluconeogenesis and glycogenolysis will become inhibited

Question 20

What sugar does the following tests test for:

1. Urine Dipstick Test

2. Copper Reduction Test

Answer 20

1. Glucose
2. All sugars (glucose, fructose, galactose)

Question 21

What would be the recommended treatment for a patient with Hereditary Fructose Intolerance?

Answer 21

Decreased intake of:

• fructose
• sucrose (fructose + sucrose)

Question 22

Galactokinase Deficiency

1. What enzyme is deficient? What accumulates?
2. Symptoms

Answer 22

1. Galactokinase —> Accumulation of Galactitol

2.

Galactosemia + Galactosuria

Infantile Cataracts

Failure to track objects

Failure to develop a social smile

Question 23

Classic Galactosemia

1. Deficient Enzyme and accumulated substance
2. Symptoms

Answer 23

1. Galactose-1-Phosphate Uridyltransferase

(Accumulation of Galactose-1-Phosphate and Galactitol)

2. Severe Galactosemia

Failure to thrive + intellectual disability

Jaundice + Hepatomegaly

Infantile Cataracts

Question 24

Fill in the blanks

Glucose ——-(?????)—–>

Sorbitol —–(?????)—–>

Fructose

Answer 24

Aldose Reductase

Sorbitol Dehydrogenase

Question 25

Why do some cells convert **glucose** to **_sorbitol_** and then to **fructose**? How can this be dangerous?

Answer 25

It is an alternative method of trapping glucose in the cell Some cells **lack sorbitol dehydrogenase** which can result in sorbitol accumulation in the cell which can cause **osmotic damage**

Question 26

Which types of tissue are most susceptible to osmotic damage due to **sorbitol accumulation?**

Answer 26

****_L_**ens** ---\> cataracts ****_R_**etina** ****_K_**idney** ****_S_**chwann Cells** ---\> peripheral neuropathy "Sorbitol **_L_**u**_RKS_**"

Question 27

What are the **_Glucogenic_** amino acids?

Answer 27

**Methionine** **Histidine** **Valine** "I **met** **his** **val**entine, she is sweet/glucogenic"

Question 28

What are the **_ketogenic_** amino acids?

Answer 28

**Lysine** **Leucine**

Question 29

What are the **acidic** amino acids? What are the **basic** amino acids?

Answer 29

Acidic: **Aspartic Acid** & **Glutamic Acid** Basic: **Histidine, Arginine, Lysine**

Question 30

**_Arginase Deficiency_** 1. What cant be produced? 2. How does it present?

Answer 30

1. **Urea and Ornithine** (from arginine) 2. **abnormal gait** + **growth delay**

Question 31

Which amino acid **transports _ammonia_ (NH₃) to the liver** so it can enter the urea cycle?

Answer 31

**_Alanine_**

Question 32

**_Hyperammonemia_** 1. What are the 2 main ways it can occur? 2. Pathophysiology

Answer 32

1. **- Liver disease** **- urea cycle enzyme deficiencies** 2. Excess NH3 **_depletes Glutamate (GABA)_** which disrupts neurotransmission

Question 33

**_Hyperammonemia_** 1. How does it present? 2. Treatment

Answer 33

- **_Asterixis_** (flapping wrist tremor) - **Somnolence** (desire to sleep) - **vomitting** **-tachypnea** - **cerebral edema** Treatment: limit protein in diet (so there is less a.a. catabolism)

Question 34

**_Ornithine Transcarbamylase deficiency_** 1. What cannot be produced? 2. What substance builds up?

Answer 34

1. **Citruline** cannot be produced from **ornithine** and **carbomyl phosphate** 2. Carbomyl phosphate builds up which gets converted to **_orotic acid_**

Question 35

**_Ornithine Transcarbamylase Deficiency_** 1. How does it present? 2. What is found in blood and urine?

Answer 35

1. Symptoms of **hyperammonemia** (**asterixis, sleepiness, vomitting, tachypnea, confusion**) 2. **_Orotic acid_** (found in blood and urine)

Question 36

**_Phenylketonuria (PKU)_** 1. What deficiencies result in PKU? 2. What amino acid becomes essential?

Answer 36

1. - **_Phenylalanine Hydoxylase_** (converts Phenylalanine to tyrosine) - **_BH₄_** (cofactor for phenylalanine hydroxylase) 2. **_Tyrosine_**

Question 37

**_Phenylketonuria (PKU)_** 1. How does it present? 2. Treatment

Answer 37

1. **- Musty body odor** **- fair/pale complexion** **- intellectual disability** **- seizures** 2. Increased tyrosine, decreased phenylalanine

Question 38

**_Maternal PKU_** 1. Why does it occur? 2. How does the infant present?

Answer 38

1. Mother lacks proper dietary therapy during pregnancy 2. Infant presents with: **- microcephaly** **- intellectual disability** **- growth retardation** **- congenital heart defects**

Question 39

**_Alkaptonuria_** 1. What enzyme is deficient? 2. What substance accumulates?

Answer 39

1. **Homogentisate Oxidase** (converts Homogentisic Acid to fumarate which enters TCA) 2. **Homogentisic Acid**

Question 40

**_Alkaptonuria_** 1. How does it present? 2. What are the urinary findings?

Answer 40

1. **Bluish/black connective tissue, sclerae and ear cartillage** 2. **Urine turns black on prolonged exposure to air**

Question 41

**_Maple Syrup Urine Disease_** 1. What **enzyme** is deficient? 2. What **cofactor** is needed for that enzyme? 3. What **proteins** cannot be broken down?

Answer 41

1. **Branched-chain alpha-ketoacid dehydrogenase** 2. **Thiamine (B₁)** **3. Branched amino acids** **(isoleucine, leucine, valine)** **"I L**ove **V**ermont **maple syrup** from **B₁ranched** trees**"**

Question 42

**_Maple Syrup Urine Disease_** 1. Presentation 2. Treatment

Answer 42

1. **Urine smells like _maple syrup / burnt sugar_** **Vomitting** **Poor feeding** 2. restrictiction of **isoleucine**, **leucine** and **valine** **Thiamine (B1)** supplementation

Question 43

Deficiency of which 2 different enzymes can result in **_Homocystinuria_**?

Answer 43

1. **_Cystathionine Synthase Deficiency_** (homocysteine --\> cystathione --\> **cysteine**) 2. **_Methionine Synthase Deficiency_** (homocysteine ---\> **methionine**)

Question 44

How does **_Homocystinuria_** clasically present?

Answer 44

**_H_**omocystinuria **_O_**steoporosis **_M_**arfanoid Habitus **_O_**ccular changes (eyes downward and inward) **_C_**ardiovascular effects (thombosis and atherosclerosis) k**_Y_**phosis "**_HOMOCY_**steinuria"

Question 45

What does **homocystinuria** often result in cardiovascular events such as **MIs** and **strokes**?

Answer 45

Homocysteine is **prothombotic**

Question 46

**_Cystinuria_** 1. Where in the **kidney** does the defect occur? 2. Which substances cannot be absorbed? 3. What is the **diagnostic test**?

Answer 46

1. **Proximal Convoluted Tubule (PCT)** 2. ****_C_**ystine, **_O_**rnithine, **_L_**ysine, **_A_**rginine** **"COLA"** 3. **Urinary cyanide-nitroprusside test**

Question 47

How do **cystine stones** appear on microscopy? Gross visual appearance?

Answer 47

**Hexagonal shaped** **"SIX**tine stone**"** **Staghorn Calculi** (most commonly in *children*)