Midterm 1 (Lec 3)

Question 1

Biotin structure (b)

Answer 1

Bicycle ring structure

Biotin - free biotin
- ureido ring
- sulfur’s ring W a valeric acid side chain

Biocytin - bound biotin
- biotin plus lysine: biotin likes binding lysine in food
- step in proteolysis during biotin digestion
- biotin also binds to enzymes via lysine: holocarboxylase

PDF OF STRUCTURE

Question 2

Biotin absorption

Answer 2

Bound to proteins in foods

PROTEASES cleave biocytin from the proteins

BIOTINIDASE cleaves biocytin to biotin plus lysine - frees biotin

Free biotin is absorbed

All occurs in intestines

Question 3

Biotin Metabolic function

Answer 3

Functions as part of coenzyme for carboxylase

Serves as a CO2 donor to substrates - CO2 fixation occurs

FOUR unique enzymes that depends on biotin - all involved in macronutrient and energy metabolism

Question 4

Biotin Dependent enzymes

Answer 4

PYRUVATE carboxylase
- glucose metabolism
- important step for gluconeogenesis
- regenerates OAA for TCA cycle

ACETYL CoA carboxylase
- fatty acid synthesis

PROPIONYL CoA carboxylase
- source of energy- entry into TCA

3-METHYLCROTONYL CoA carboxylase
- amino acid metabolism- leucine degradation

SEE PDF

Question 5

Holocarboxylase

Answer 5

General term to describe biotin dopendent enzymes with biotin attached to them (they become “whole” and can function)

As with all coenzymes there must be attachment to the enzyme (physical interaction)

HOLOCARBOXYLASE SYNTHASE is needed to attach biotin to the lysine residue of the enzyme

Once biotin is attached to the enzyme, the enzyme is now classified as a holocarboxylase

Question 6

Egg white injury disease

Answer 6

Study where rats fed raw egg whites developed syndrome of dermatitis hair loss etc

AVIDIN is a glycoprotein in egg white that binds biotin very tightly

Once BIOTIN AVIDIN COMPLEX is formed it’s irreversible and not broken down - prevents absorption of biotin and causes deficiency

SOLUTION: AVIDIN IS DENATURED BY COOKING SO IT WILL NOT BIND BIOTIN

Question 7

Bacterial synthesis of biotin

Answer 7

Biotin CAN be synthesized by human intestinal bacteria BUT this does not replace the need for it in diet

Also implications for long term antibiotic use

Question 8

Biotin deficiency

Answer 8

3 ways to become biotin deficient
-Not eating it in diet
- unable to absorb it (not having the biotinidase enzyme that frees biotin from lysine)
- unable to utilize it after absorption (biotinidase works fine but hydro carboxylase synthase does NOT)

Deficiency causes
- rude yes dietary intake
- biotin free TPN over long periods (IV NUTRIENTS)
- consumption of raw egg whites (unlikely)

Symptoms
- neurological symptoms: depression, lethargy, hallucinations, paresthesia of extremities
- hair skin and nail problems: hair thinning, dermatitis, BRITTLE NAILS

Deficiency is RARE (because we also synthesize it naturally)

Question 9

Biotinidase deficiency

Answer 9

Included as a screening for newborns

Without biotinidase, we are unable to convert biocytin (biotin plus lysine) into free biotin

Question 10

Holocarboxylase synthase deficiency

Answer 10

Holocarboxylase synthase attaches biotin to lysine residue of carboxylase enzymes

There is single and multiple carboxylase deficiency - immunodeficiency disease

Question 11

Biotin deficiency - biochemical results

Answer 11

Decrease in biotin dependent enzymes (and therefore an increase in their substrates - they cannot catalyze the reactions they’re a part of as fast as they usually do)

Ex- decreased Pyruvate carboxylase decreases gluconeogenesis and therefore increases Pyruvate and lactate

Decreased acetyl CoA carboxylase decreases fatty acid synthesis therefore increasing acetyl CoA (risk for ketosis and impaired serum lipids)

CAUSES ACCUMULATION OF BIOTIN SUBSTRATES in urine since enzymes are not working : beta methylcrotonate, beta hydroxyisovalerate, beta hydroxypropionate

Question 12

How can biotin deficiency occur

Answer 12

Decreased intake - long term TPN without biotin in it

Decreased absorption - AVIDIN

Deficiency in key enzymes - biotinidase (absorption), holocarboxylase (utilization)

Daily requirement affected by
- raw egg white
- biotinidase deficiency
- drug interactions
- pregnancy

Question 13

Biotin medical pitfalls

Answer 13

• failure to diagnose biotin deficiency promptly
• failure to include biotin in TPN solutions
• failure to recognize some anticonvulsants can interfere with biotin absorption (not only biotinidase that can prevent absorption)
• failure to recognize antibiotic use long term can cause biotin deficiency

Question 14

PANTOTHENIC acid (B5) and structure

Answer 14

Can be found in all living cells - intestinal enzymes convert it’s many forms into free pantetheine for absorption

Coenzyme structure
- part of two major coenzymes :
- COENZYME A (CoA)
- ACYL CARRIER PROTEIN (ACP)

Both contain SH ( thiol) group - directly involved in biochemical reactions

Question 15

Coenzyme A

Answer 15

Coenzyme form of pantothenic acid

Synthesized from;
- PANTOTHENIC ACID
- CYSTEINE
- ATP

also abbreviated as CoASH

Question 16

CoA metabolic role

Answer 16

Transfer of acetyl groups (2 carbon) also known as acetyl transfer reactions

Connect to SH groups - where action occurs

Central to nutrient and energy metabolism

Many anabolic and catabolic fates - TCA, fatty acid synthesis/oxidation

Question 17

CoA transferring acetyl groups examples

Answer 17

Energy production
- CoA involved in multiple steps of TCA cycle
- ex; Pyruvate to acetyl CoA

Fatty acid regulation
- fatty acid synthesis from acetyl CoA
- fatty acid oxidation to acetyl CoA (beta oxidation)

Cholesterol synthesis
- HMG CoA reductase is the rate limiting enzyme

Question 18

Acyl carrier protein (ACP)

Answer 18

Another coenzyme form of pantothenic acid - thiol group attached to serine

Part of enzyme complex called fatty acid synthase ;
- ACP is taking over the role of CoA in this situation
- fatty acid synthesis is a sequential process infilling addition of ACYL groups to intermediates to form palmitate

Question 19

ACP metabolic role

Answer 19

FATTY ACID SYNTHESIS
- ACP is part of fatty acid synthase as an enzyme complex
- PANTOTHENIC acid is a prosthetic group of ACP
- ACP serves as a chaperone for FA synthesis (when we need fat, ACP is added to the fatty acid enzyme complex ACP SYNTHETASE - when we don’t need fat, ACP is removed ACP HYDROLASE)

*

Question 20

PANTOTHENIC acid deficiency

Answer 20

Rare since it’s in a lot of foods
Diet would need to be very unusual

BURNING FEET SYNDROME
- pains in toes and soles of feet
- WW2 prisoners of war
- poorly nourished in the Far East

Question 21

PANTOTHENIC acid for cholesterol and triglyceride reduction

Answer 21

PANTOTHENIC acid is involved in synthesis of cholesterol and fatty acids

Specific form of pantethine has shown to reduce cholesterol and triglycerides
But pantothenic acid form cannot

Dose around 600 mg/day - way more than dietary requirement