Midterm 1 (Lec 3) Flashcards
Biotin structure (b)
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
Biotin absorption
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
Biotin Metabolic function
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
Biotin Dependent enzymes
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
Holocarboxylase
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
Egg white injury disease
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
Bacterial synthesis of biotin
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
Biotin deficiency
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)
Biotinidase deficiency
Included as a screening for newborns
Without biotinidase, we are unable to convert biocytin (biotin plus lysine) into free biotin
Holocarboxylase synthase deficiency
Holocarboxylase synthase attaches biotin to lysine residue of carboxylase enzymes
There is single and multiple carboxylase deficiency - immunodeficiency disease
Biotin deficiency - biochemical results
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
How can biotin deficiency occur
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
Biotin medical pitfalls
- 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
PANTOTHENIC acid (B5) and structure
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
Coenzyme A
Coenzyme form of pantothenic acid
Synthesized from;
- PANTOTHENIC ACID
- CYSTEINE
- ATP
also abbreviated as CoASH
CoA metabolic role
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
CoA transferring acetyl groups examples
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
Acyl carrier protein (ACP)
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
ACP metabolic role
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)
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PANTOTHENIC acid deficiency
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
PANTOTHENIC acid for cholesterol and triglyceride reduction
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
